recurrent depression case study

Clinical Practice Guideline for the Treatment of Depression

Case Examples

Examples of recommended interventions in the treatment of depression across the lifespan.

Children/Adolescents

A 15-year-old Puerto Rican female

The adolescent was previously diagnosed with major depressive disorder and treated intermittently with supportive psychotherapy and antidepressants. Her more recent episodes related to her parents’ marital problems and her academic/social difficulties at school. She was treated using cognitive-behavioral therapy (CBT).

Chafey, M.I.J., Bernal, G., & Rossello, J. (2009). Clinical Case Study: CBT for Depression in A Puerto Rican Adolescent. Challenges and Variability in Treatment Response. Depression and Anxiety , 26, 98-103. https://doi.org/10.1002/da.20457

Sam, a 15-year-old adolescent

Sam was team captain of his soccer team, but an unexpected fight with another teammate prompted his parents to meet with a clinical psychologist. Sam was diagnosed with major depressive disorder after showing an increase in symptoms over the previous three months. Several recent challenges in his family and romantic life led the therapist to recommend interpersonal psychotherapy for adolescents (IPT-A).

Hall, E.B., & Mufson, L. (2009). Interpersonal Psychotherapy for Depressed Adolescents (IPT-A): A Case Illustration. Journal of Clinical Child & Adolescent Psychology, 38 (4), 582-593. https://doi.org/10.1080/15374410902976338

© Society of Clinical Child and Adolescent Psychology (Div. 53) APA, https://sccap53.org/, reprinted by permission of Taylor & Francis Ltd, http://www.tandfonline.com on behalf of the Society of Clinical Child and Adolescent Psychology (Div. 53) APA.

General Adults

Mark, a 43-year-old male

Mark had a history of depression and sought treatment after his second marriage ended. His depression was characterized as being “controlled by a pattern of interpersonal avoidance.” The behavior/activation therapist asked Mark to complete an activity record to help steer the treatment sessions.

Dimidjian, S., Martell, C.R., Addis, M.E., & Herman-Dunn, R. (2008). Chapter 8: Behavioral activation for depression. In D.H. Barlow (Ed.) Clinical handbook of psychological disorders: A step-by-step treatment manual (4th ed., pp. 343-362). New York: Guilford Press.

Reprinted with permission from Guilford Press.

Denise, a 59-year-old widow

Denise is described as having “nonchronic depression” which appeared most recently at the onset of her husband’s diagnosis with brain cancer. Her symptoms were loneliness, difficulty coping with daily life, and sadness. Treatment included filling out a weekly activity log and identifying/reconstructing automatic thoughts.

Young, J.E., Rygh, J.L., Weinberger, A.D., & Beck, A.T. (2008). Chapter 6: Cognitive therapy for depression. In D.H. Barlow (Ed.) Clinical handbook of psychological disorders: A step-by-step treatment manual (4th ed., pp. 278-287). New York, NY: Guilford Press.

Nancy, a 25-year-old single, white female

Nancy described herself as being “trapped by her relationships.” Her intake interview confirmed symptoms of major depressive disorder and the clinician recommended cognitive-behavioral therapy.

Persons, J.B., Davidson, J. & Tompkins, M.A. (2001). A Case Example: Nancy. In Essential Components of Cognitive-Behavior Therapy For Depression (pp. 205-242). Washington, D.C.: American Psychological Association. http://dx.doi.org/10.1037/10389-007

While APA owns the rights to this text, some exhibits are property of the San Francisco Bay Area Center for Cognitive Therapy, which has granted the APA permission for use.

Luke, a 34-year-old male graduate student

Luke is described as having treatment-resistant depression and while not suicidal, hoped that a fatal illness would take his life or that he would just disappear. His treatment involved mindfulness-based cognitive therapy, which helps participants become aware of and recharacterize their overwhelming negative thoughts. It involves regular practice of mindfulness techniques and exercises as one component of therapy.

Sipe, W.E.B., & Eisendrath, S.J. (2014). Chapter 3 — Mindfulness-Based Cognitive Therapy For Treatment-Resistant Depression. In R.A. Baer (Ed.), Mindfulness-Based Treatment Approaches (2nd ed., pp. 66-70). San Diego: Academic Press.

Reprinted with permission from Elsevier.

Sara, a 35-year-old married female

Sara was referred to treatment after having a stillbirth. Sara showed symptoms of grief, or complicated bereavement, and was diagnosed with major depression, recurrent. The clinician recommended interpersonal psychotherapy (IPT) for a duration of 12 weeks.

Bleiberg, K.L., & Markowitz, J.C. (2008). Chapter 7: Interpersonal psychotherapy for depression. In D.H. Barlow (Ed.) Clinical handbook of psychological disorders: a treatment manual (4th ed., pp. 315-323). New York, NY: Guilford Press.

Peggy, a 52-year-old white, Italian-American widow

Peggy had a history of chronic depression, which flared during her husband’s illness and ultimate death. Guilt was a driving factor of her depressive symptoms, which lasted six months after his death. The clinician treated Peggy with psychodynamic therapy over a period of two years.

Bishop, J., & Lane , R.C. (2003). Psychodynamic Treatment of a Case of Grief Superimposed On Melancholia. Clinical Case Studies , 2(1), 3-19. https://doi.org/10.1177/1534650102239085

Several case examples of supportive therapy

Winston, A., Rosenthal, R.N., & Pinsker, H. (2004). Introduction to Supportive Psychotherapy . Arlington, VA : American Psychiatric Publishing.

Older Adults

Several case examples of interpersonal psychotherapy & pharmacotherapy

Miller, M. D., Wolfson, L., Frank, E., Cornes, C., Silberman, R., Ehrenpreis, L.…Reynolds, C. F., III. (1998). Using Interpersonal Psychotherapy (IPT) in a Combined Psychotherapy/Medication Research Protocol with Depressed Elders: A Descriptive Report With Case Vignettes. Journal of Psychotherapy Practice and Research , 7(1), 47-55.

Case Study of a 44-Year-Old Patient with a Moderate Recurrent Depressive Disorder (ICD-10 F 33.1) from Psychodynamic Point of View

First Online: 04 May 2021

Cite this chapter

Christos Charis 3

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Mrs. X is a 44-year-old divorced mother of one (daughter) who presented with a major depression of moderate intensity which was already chronic as she came to me for therapy (09/17). The onset of the depression was present when Mrs. X was 34 years old. She decided to rent a flat with her boyfriend who she loved. She developed severe panic attacks at that moment and became very depressed. Again, Mrs. X became severely depressed at the age of 41. The patient had a course of electroconvulsive therapy (ECT, 22 electroshocks) and after that behaviour therapy for 1 year. All those treatments helped her to feel better, but she felt exhausted every day and had a low mood. The psychodynamic analysis showed two conflicts, a narcissistic conflict and an autonomous-dependent conflict, as they are defined in the Operationalized Psychodynamic Diagnosis-2 (OPD-2). These conflicts are due to the treatment of Mrs. X by her parents and because of her disappointing experiences when she had to escape from her own country when she was 13 years old. She had to act against her own will. We can analyse the psychodynamics of Mrs. X with regard to the concept of Sidney Blatt, a psychoanalyst (Blatt and Blass, Development and vulnerabilities on close relationships, 1996; Blatt et al., Psyche, 59(9–10), 864–891, 2005). Blatt investigated areas that concern the everyday experiences of depressive people. The first core theme is “loneliness, weakness, helplessness and abandonment. Desires to be cared for, loved and protected”. This factor was called “dependency” or “anaclitic”. The second factor is preoccupation with self-definitional areas (“introjective”: harsh self-criticism; perfectionism). Introjective depression is characterized by a tendency towards self-criticism and self-evaluation. Our patient did not learn to trust other people because of her very disappointing experiences with her parents. This led to a very weak self-consciousness and an excessively perfectionistic ego ideal. These traits have played an important role for the onset of chronic depression of Mrs. X. The depressive symptoms of Mrs. X have been relieved even more in a psychodynamic treatment which is ongoing. (Until July 2020, 90 sessions have taken place.) She has succeeded in partially reducing her demands on herself.

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Charis, C. (2021). Case Study of a 44-Year-Old Patient with a Moderate Recurrent Depressive Disorder (ICD-10 F 33.1) from Psychodynamic Point of View. In: Charis, C., Panayiotou, G. (eds) Depression Conceptualization and Treatment. Springer, Cham. https://doi.org/10.1007/978-3-030-68932-2_6

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Published: 27 April 2017

A case of recurrent depressive disorder presenting with Alice in Wonderland syndrome: psychopathology and pre- and post-treatment FDG-PET findings

Tatsushi Yokoyama 1 ,
Tsuyoshi Okamura 1 ,
Miwako Takahashi 2 ,
Toshimitsu Momose 2 &
Shinsuke Kondo 1

BMC Psychiatry volume 17 , Article number: 150 ( 2017 ) Cite this article

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Alice in Wonderland syndrome (AIWS) is a rare neuropsychiatric syndrome that typically manifests in distortion of extrapersonal visual image, altered perception of one’s body image, and a disturbed sense of the passage of distance and time. Several conditions have been reported to contribute to AIWS, although its biological basis is still unknown. Here, we present the first case demonstrating a clear concurrence of recurrent depressive disorder and AIWS. The clinical manifestations and pre- and post-treatment fluorodeoxyglucose positron-emission tomographic (FDG-PET) images provide insights into the psychopathological and biological basis of AIWS.

Case presentation

We describe a 63-year-old Japanese male who developed two distinct episodes of major depression concurrent with AIWS. In addition to typical AIWS perceptual symptoms, he complained of losing the ability to intuitively grasp the seriousness of news and the value of money, which implies disturbance of high-order cognition related to estimating magnitude and worth. Both depression and AIWS remitted after treatment in each episode. Pre-treatment FDG-PET images showed significant hypometabolism in the frontal cortex and hypermetabolism in the occipital and parietal cortex. Post-treatment images showed improvement of these abnormalities.

Conclusions

The clinical co-occurrence of depressive episodes and presentation of AIWS can be interpreted to mean that they have certain functional disturbances in common. In view of incapacity, indifference, devitalization, altered perception of one’s body image, and disturbed sense of time and space, the features of AIWS analogous to those of psychotic depression imply a common psychopathological basis. These high-order brain dysfunctions are possibly associated with the metabolic abnormalities in visual and parietotemporal association cortices that we observed on the pre- and post-treatment FDG-PET images in this case, while the hypometabolism in the frontal cortex is probably associated with depressive symptoms.

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Alice in Wonderland syndrome (AIWS) is a rare neuropsychiatric syndrome, which Todd [ 1 ] named after the character created by Lewis Carroll. Collective manifestations of AIWS include distortion of extrapersonal visual image (micropsia, macropsia, metamorphopsia, teleopsia, and pelopsia), altered perception of one’s body image, and a disturbed sense of the passage of distance and time [ 2 ].

Many conditions have been reported to contribute to AIWS, and Lanska et al. [ 2 ] indicates that viral infection and migraine are the two most commonly identified causes, occurring preferentially in young individuals. To the best of our knowledge, only two reports to date have associated AIWS with a depressive disorder [ 3 , 4 ], neither of which clearly showed the concurrent nature of major depressive episodes and AIWS.

Evidence from a number of studies using fluorodeoxyglucose positron emission tomography (FDG-PET) indicates that specific cortical regions, primarily in the frontal cortex, are related to mood disorders. However, the results from imaging studies have not yielded a clear story, and many conflict with each other [ 5 , 6 , 7 ]. One of the more consistent findings with regard to depression, is that hypometabolism in the frontal cortex is characteristic in patients with depressive episodes, and can be partially reversed by successful treatment. In contrast, the biological basis of AIWS is even less clear, although a few studies have made attempts studying it using functional brain imaging [ 8 , 9 , 10 , 11 ].

Here, we present a case of an older patient whose recurrent depressive episodes and AIWS emerged and remitted simultaneously with successful treatment with antidepressants, antipsychotics, and electroconvulsive therapy (ECT). This is the first report showing the concurrent and recurrent nature of, depressive episodes and AIWS, and the strong association between the two. The clinical manifestations and pre- and post-treatment FDG-PET images provide insights into the psychopathological and biological basis of AIWS.

Here, we report the case of a 63-year-old Japanese man with no medical or psychiatric history, except for type-2 diabetes mellitus and essential hypertension. He had no previous history of psychotropic drug use, including antidepressants and antipsychotics. Additionally, he had no developmental abnormalities or neurodevelopmental disorders. He held a steady job from college graduation until retirement age, and his wife described his premorbid personality as dependable, sociable, and patient. He had no family history of psychiatric disorders, migraine, or epilepsy.

One year before his first admission to an inpatient psychiatric unit, he started experiencing mild depressive moods and fatigue that did not disrupt his day-to-day functioning. Two months before the first hospital admission, he began complaining about typical AIWS symptoms, including micropsia, altered perception of his body image, and a disturbed sense of the passage of distance and time. All sorts of objects in his environment, such as buildings and cars, looked extremely small to him. He gave up driving because cars looked so small that he lost his sense of speed and distance in relation to the cars around him. Nearby objects also looked very small, with the single exception of pill strips that he had difficulty opening. Moreover, even though he knew it was not possible, he felt as if he could ‘step over’ long distances in a flash, such as the 50 km from his suburban town to the center of Tokyo. Additionally, he felt that days passed extremely quickly, as if in a single moment. He also sometimes felt his body was slightly enlarged or shrunken compared with normal. These AIWS symptoms persisted all day long during the depressive episodes.

In addition to the typical AIWS symptoms described above, he also complained of disturbances in high-order cognition. For instance, he said, “I cannot sense how important the news is. For example, when I see news about a serial murder on television, I can understand intellectually how sad it is, but I cannot realize it emotionally”. Similarly, he said, “I cannot appreciate the value of money. Even if there were a ¥10,000 bill in front of me, I wouldn’t care about it because I can’t realize how much value it would have”. Although his bowel movements and urination were normal, he complained of a decreased urge to defecate and urinate.

The depressed mood, loss of interest and pleasure, psychomotor retardation, fatigue, and reduced concentration gradually worsened. He was referred to a neurologist. Organic causes were ruled out as follows: his blood-sugar level and blood pressure were well controlled with insulin injections and oral medications; he was a non-drinker, had no history of head trauma, and took no medications associated with adverse reactions that could mimic depression, such as beta-blockers and cimetidine. Neurological examinations and laboratory tests including endocrine evaluations and an HIV test, electroencephalography, and brain magnetic resonance imaging (MRI) detected no abnormalities. He was then referred to a psychiatrist. After confirming that he was not experiencing a manic episode, was not using illicit drugs, and had not experienced any recent stressful life events, he was diagnosed as having a severe depressive episode with AIWS. His condition worsened to the degree that he could not continue working despite taking paroxetine, and he was hospitalized for the first time.

At this first admission, he was bed-ridden all day because of severe depressive symptoms. Administration of amitriptyline (75 mg/day) and perphenazine (6 mg/day) induced gradual improvement of depressive and AIWS symptoms. He was discharged on day 47 after he had remitted almost completely from the depressive episode, with the exception of easily becoming fatigued and waking at night. At that time, he was also completely remitted from AIWS. His day-to-day functioning returned to normal, and his work and life continued as they had before the episode began.

Three years after discharge, he relapsed into another major depressive episode, again simultaneously presenting with AIWS. The symptoms worsened despite the use of amitriptyline (50 mg/day) and aripiprazole (6 mg/day) in the outpatient clinic. The Visual Perception Test for Agnosia detected nothing abnormal. His thoughts became stunted and he became very inactive, lying in bed all day. He continuously refused inpatient treatment because he delusionally believed he was too poor. Upon the strong recommendation from his family, 8 months after this recurrence, he was admitted to the hospital with recurrent severe depressive symptoms and AIWS at the age of 67 years.

At this second admission, he was alert and oriented, but had prolonged speech latency and spoke in a slow and quiet manner without making eye contact. His face was unshaven and he did not smile. Dementia was ruled out as a plausible cause of his symptoms for the following reasons: 1) his Mini-Mental State Examination (MMSE) score was 28/30 during this depressive episode, 2) he made a complete recovery from the observed reduction in concentration and processing speed after treatment of the first episode, 3) he exhibited no other signs of recognizable cognitive decline such as impaired executive function, learning, memory, language, or social recognition, and 4) he did not exhibit any typical symptoms of common dementia subtypes, such as amnesia, fluctuating cognition, visual hallucinations, extrapyramidal symptoms, or behavioral symptoms. Evidence of depressive symptoms and AIWS was comparable between the first and second episodes. He scored 30/63 on the Beck Depression Inventory-II (BDI-II), indicating severe depression. An ophthalmologist confirmed no eye/visual abnormalities with the exception of bilateral cataracts. Pre-therapy FDG-PET was performed as described below. After 2 weeks of maprotiline (75 mg/day) had no effect, twice-weekly ECT, duloxetine (60 mg/day) and mirtazapine (45 mg/day) were administered. He remitted completely from AIWS and almost completely from the depressive episode after 12 ECT sessions, except for a mild reduction in concentration. He scored 12/63 on the BDI-II, which also indicated significant recovery from depression. He was discharged after 75 days, just after post-therapeutic FDG-PET was performed.

FDG-PET acquisition, visual inspection, and statistical analysis

We obtained the pre- and post-treatment FDG-PET images of the brain during the second admission. The patient was kept at rest in supine posture with a blinder in a quiet and dim room from 10 min before each PET examination until the end of the scan. Scans were recorded with a PET scanner (Advance NXi; GE Medical Systems, Milwaukee, WI, USA) 45 min after the injection of 296 MBq FDG.

Upon visual inspection, the pre-treatment FDG-PET images depicted moderate hypometabolism in the frontal cortex and relative hypermetabolism in the occipital and parietal cortices (Fig. 1a ). These abnormalities improved slightly after treatment (Fig. 1b ).

Axial pre- and post-treatment brain FDG-PET images. The color scale ranges from zero to the maximum value within the brain. a Pre-treatment images show hypometabolism in the bilateral frontal cortex ( white arrows ) and relative hypermetabolism in the bilateral occipital and parietal cortex ( red arrows ). b Post-treatment images show slight normalization of these abnormalities

Statistical analysis was performed in the following steps: (1) morphological co-registration between pre-and post-treatment FDG-PET; (2) normalization of voxel values to the global mean voxel counts using proportional scaling; (3) subtraction of pre-treatment from post-treatment images to obtain pre-post difference images; (4) mean and standard deviations of voxel values were calculated for the difference images; and (5) identification of area with statistically significant difference, using a cutoff value of z > 2 and extent threshold k > 200. These methods are part of the standard process for subtracting ictal single photon emission computed tomography (SPECT) coregistered to MRI (SISCOM), which is generally used for comparing ictal and interictal SPECT images in epileptic patients [ 12 ]. The statistical analysis showed that metabolism decreased after treatment in the posterior half of the cerebral cortex, including the posterior part of the bilateral temporal cortex, the occipital cortex, the inferior part of parietal cortex, precuneus, and posterior cingulate cortex (Fig. 2 ). No area showed statistically significant increases in metabolism after treatment.

Within-subject comparison between pre- and post-treatment in our patient. The colored areas indicate significant decreases in metabolism from pre- to post-treatment, with the color scale (z score) ranging from 2 to 5

Synchronicity of depressive episodes and AIWS

In this case study, we described an older patient presenting with two distinct major depressive episodes, both of which occurred simultaneously with episodes of AIWS. Both sets of symptoms remitted completely after standard treatment for psychotic depression (i.e., an antidepressant plus an antipsychotic, or ECT), and we excluded the potential influence of dementia and other organic causes. This is the first report that clearly shows a link between recurrent depressive disorder and AIWS. The clinical co-occurrence of depressive episodes and AIWS can be interpreted as arising from common functional disturbances. Below we elaborate on the relationship between AIWS and severe depression from the viewpoints of psychopathology and of neuroimaging.

AIWS presenting in the course of psychotic depression

Lanska et al. reported that a variety of conditions contribute to AIWS, including infection, migraine, toxic encephalopathy, major depression, epileptic seizures, medications, and stroke [ 2 ]. However, to date, only two case reports have shown an association between depressive episodes and AIWS [ 3 , 4 ]. Mizuno et al. reported a 54-year-old man who exhibited depressive symptoms with AIWS (metamorphopsia, disturbed sense of passage of time, and distortion of body image). In that case, AIWS disappeared 2 days after admission despite no improvement in depressive symptoms [ 3 ]. Bui et al. reported a 74-year-old man who showed severe depressive symptoms with persecutory and somatic delusions (his stools being contaminated) and AIWS (he thought his hands and feet were shorter than usual), all of which remitted completely with ECT [ 4 ]. Importantly, both cases presented with psychotic depression during the clinical course. In Mizuno et al., the patient developed a delusion of culpability and in Bui et al., the patient developed persecutory and somatic delusions. Our patient also transiently developed delusions (he believed he was poor) during the depressive episode. The clinical presentation of these three cases indicates an association between AIWS and psychotic depression in particular.

Psychopathological similarities between AIWS and psychotic depression

Patients with psychotic depression tend to regard themselves as being useless, or consider everything meaningless. They also claim to lose a grasp on proper emotions and visceral sensations. Stanghellini et al. extensively reviewed the psychopathology of depression and described the qualitative features of experience in patients with psychotic depression to include incapacity, indifference, timelessness, and bodily devitalization [ 13 ]. Failure to sense the significance or magnitude of external facts or objects, such as the difficulty with news and money seen in our patient, can be viewed as being part of the incapacity or indifference categories. Being unable to estimate or sense one’s own urge to urinate or make bowel movements can also be explained by indifference or devitalization. According to Stanghellini et al. constriction of time and body experiences, as well as shrinking and extension of space, occur in major depression. Perceptual alterations in space, time, and body seem to be notably analogous to that of AIWS. Thus, we argue that comorbidity of AIWS and psychotic depression in our case was not by chance, but occurred because of a common underlying brain dysfunction.

Interpretation of FDG-PET results

The frontal cortex hypometabolism in our case was probably related to the depressive symptoms (Fig. 1 ). Hosokawa et al. reported that euthymic patients exhibited fewer areas with significantly low metabolism than did depressed patients in the cross-sectional study [ 5 ]. In our case, the decreased metabolism of bilateral frontal cortex and anterior cingulate cortex during the second depressive episode improved after treatment, although these alterations were not statistically significant. These results are consistent with many studies demonstrating that metabolism in the frontal cortex decreases in patients with depressive episodes and can be partially reversed by treatment [ 5 , 6 ].

The significant metabolic abnormalities and alterations in the posterior half of the cerebral cortex are the main characteristics of our case (Figs. 1 , 2 ). These regions include the primary visual cortex, precuneus, posterior cingulate, and temporal, parietal, and extrastriate cortices. The abnormalities in these association cortices possibly correspond to positive symptoms in our case, such as delusions of poverty or experiencing alterations in space, time, and body, which are not simply perceptual, but also include high-order cognitive disturbances. The parieto-occipital hypermetabolism in our case might also be associated with a common underlying abnormality that occurs in both psychotic depression and AIWS, although this should be explored in future studies.

We present the first case demonstrating a clear relationship between recurrent depressive disorder and AIWS. The co-occurrence and similarities in clinical manifestations between AIWS and psychotic depression imply a common psychopathological basis. The metabolic abnormalities seen in high-order brain regions on FDG-PET images suggest a biological basis of AIWS and psychotic symptoms of depression. Careful analysis of psychiatric symptoms comparing with metabolic changes using FDG-PET provides new insights into higher-order involvements, not only primary visual perception, in AIWS and psychotic depression.

Abbreviations

Alice in Wonderland syndrome

Beck Depression Inventory-II

Electroconvulsive therapy

Fluorodeoxyglucose positron emission tomography

Mini-Mental State Examination

Magnetic resonance imaging

Subtraction ictal SPECT coregistered to MRI

Single photon emission computed tomography

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Acknowledgments

The authors are grateful to the patient and his family for their help and support in writing this case report. The authors thank Dr. Kiyoto Kasai for his general support. The authors also wish to express their deepest gratitude to Dr. Atsushi Iwata, Dr. Toshihiro Hayashi, Dr. Toji Miyagawa, and Dr. Kazuyuki Sugishita (Memory clinic of Tokyo University Hospital) for their support.

Availability of data materials

The data sets supporting the results of this article are included within the article.

Authors’ contributions

TY, TO, and SK were responsible for the clinical decisions outlined in this report. TY, MT, and SK drafted the manuscript. TO conceived the report and helped to draft the manuscript. MT performed the FDG-PET analysis. TM supported with the FDG-PET analysis. SK was critically involved in the theoretical discussion and writing the manuscript. All authors contributed to the literature review and manuscript preparation and approved the final manuscript.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

Written informed consent for the publication of the case report was obtained from the patient.

Ethics approval and consent to participate

Approval by the University of Tokyo Hospital ethics committee was obtained (3349-(4)).

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Tatsushi Yokoyama, Tsuyoshi Okamura & Shinsuke Kondo

Department of Radiology, Graduate School of Medicine, University of Tokyo, 7-3-1Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

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Yokoyama, T., Okamura, T., Takahashi, M. et al. A case of recurrent depressive disorder presenting with Alice in Wonderland syndrome: psychopathology and pre- and post-treatment FDG-PET findings. BMC Psychiatry 17 , 150 (2017). https://doi.org/10.1186/s12888-017-1314-2

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Published : 27 April 2017

DOI : https://doi.org/10.1186/s12888-017-1314-2

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Patient case navigator: major depressive disorder.

Introduction

Learning Objectives

How to perform a structured psychiatric interview
Standardized psychiatric rating scales appropriate for patients with depressive symptoms
Common barriers to adequate treatment response
How to assess and monitor patients for treatment side effects and adequate treatment response

Watch the video:

History and Examination

Medical History

Examination

History of Present Illness

Eric is a 60-year-old man who presents to his primary care nurse practitioner, Tina, with irritability, excessive sleeping, and a lack of interest in his usual hobbies, such as attending baseball games and going to the movies with his wife. He also has been spending much time at home alone, watching television, rather than spending time with his friends or wife, as he usually does. Eric recently retired from his job as a general contractor remodeling people’s kitchens and bathrooms. He enjoyed his job very much and felt a sense of pride in helping people make their homes more functional and attractive. However, his job was very physical, and at times stressful, so Eric felt it was time to retire and find something new with which to occupy his time.

Eric was diagnosed with hypothyroidism 5 years ago and has been on medication ever since. Annual lab tests indicate his thyroid levels have remained within the normal range for the past few years. He also has mild hypertension, which is well-controlled at an adequate dose.

Psychosocial History

Eric reports that he has several close friends and that he got along well with people at work. He denies a history of substance misuse and reports that he occasionally drinks a glass of wine with dinner. He does not smoke. Eric describes his marriage as “very good.” He is also close with his adult daughter and enjoys spending time with his 2 grandchildren.

At age 33, Eric experienced a period of depressed mood after losing his job. During that time, he had problems getting out of bed in the morning because he felt hopeless and sad, stopped socializing with friends, and lost about 4 lbs of body weight in 4 weeks without intentionally dieting. He sought treatment from his primary care physician, who referred him to a psychiatrist for medication and a psychologist for outpatient cognitive-behavioral therapy (CBT). Eric worked with his psychiatrist and tried 4 different selective serotonin reuptake inhibitors (SSRIs) before he ultimately found one that seemed to work for him. He and his psychiatrist decided together that he could stop taking the medication after 1 year because his mood had improved and stabilized. He saw his therapist once weekly for approximately 2.5 years and reports that CBT also helped improve his mood and functioning.

Family History

Eric reports that, throughout his life, his mother had “very low periods” when she seemed extremely sad and had trouble functioning. However, she never sought treatment for these episodes.

Eric’s physical examination indicates he is generally healthy for his age. His vital signs are all within the normal range, and the mental status examination indicates he is fully oriented and alert. Eric’s appearance is that of an older man. His affect is flat, and he has trouble making eye contact, often staring at the floor instead.

Patient Interview

Quiz #1: initial presentation and diagnosis, dsm-5 diagnostic criteria for mdd.

MDE Diagnostic Criteria

Safety Plan

Major Depressive Episode (MDE)

A. Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous function; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.

Depressed mood most of the day, nearly every day, as indicated by either subjective report or observation made by others
Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day
Significant weight loss when not dieting or weight gain, or decrease or increase in appetite nearly every day
Insomnia or hypersomnia nearly every day
Psychomotor agitation or retardation nearly every day
Fatigue or loss of energy nearly every day
Feelings of worthlessness or excessive or inappropriate guilt nearly every day
Diminished ability to think or concentrate, or indecisiveness, nearly every day
Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide

B. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of function

C. The episode is not attributable to the physiological effects of a substance or another medical condition

Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; 2013.

It is important to thoroughly review each of these 9 symptoms with your patients when assessing them for MDD.
Clinical rating scales can help identify which patients require more in-depth screening for depression.

Quiz #2: DSM-5 Diagnostic Criteria for MDD

Scales for mdd.

PHQ-9 Scale Scoring

QIDS Scale Scoring

Patient Health Questionnaire-9 (PHQ-9)

Over the last 2 weeks, how often have you been bothered by any of the following problems? (Use "✓" to indicate your answer)	Not at all	Several days	More than half the days	Nearly every day
1. Little interest or pleasure in doing things	0	1	2	3
2. Feeling down, depressed, or hopeless	0	1	2	3
3. Trouble falling or staying asleep, or sleeping too much	0	1	2	3
4. Feeling tired or having little energy	0	1	2	3
5. Poor appetite or overeating	0	1	2	3
6. Feeling bad about yourself - or that you are a failure or have let yourself or your family down	0	1	2	3
7. Trouble concentrating on things, such as reading the newspaper or watching television	0	1	2	3
8. Moving or speaking slowly that other people could have noticed? Or the opposite - being so fidgety or restless that you have been moving around a lot more that usual	0	1	2	3
9. Thoughts that you would be better off dead or of hurting yourself in some way	0	1	2	3
For Office Coding:	0	+	+	+
		=	Total Score:	_____

If you checked off any problems, how difficult have those problems made it for you to do your work, take care of things at home, or get along with other people?
Not difficult at all	Somewhat difficult	Very difficult	Extremely difficult

This scale was developed by Drs Robert L. Spitzer, Janet B.W. Williams, Kurt Kroenke, and colleagues with an educational grant from Pfizer inc. No permission required.

Scoring Criteria

0-4	No depression
5-9	Mild depression
10-14	Moderate depression
15-19	Moderately severe depression
20-27	Severe depression

Kroenke K, Spitzer RL. Psychiatric Annals. 2002;32:509-521.

The Quick Inventory of Depressive Symptomatology (QIDS)

The QIDS is a 16-item, multiple-choice questionnaire in which depressive symptoms are rated on a 0-3 scale according to severity
Items are derived from the 9 diagnostic criteria for major depressive disorder used in the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV), including sadness, loss of interest or pleasure, poor concentration or decision-making, self-outlook, suicidal ideation, lack of energy, sleep disturbance, appetite change, and psychomotor agitation
Although the QIDS was initially developed based on DSM-IV criteria, the scale is also compatible with the DSM-5. The core criteria for MDD are consistent across these editions

Rush AJ, et al. Biol Psychiatry. 2003;54(5):573-583.

0-5	Normal
6-10	Mild
11-15	Moderate
16-20	Severe
≥ 21	Very Severe

Bernstein IH, et al. Int J Methods Psychiatr Res. 2009;18(2):138-146.

Quiz #3: Scales for MDD

Treatment initiation and monitoring.

APA Guidelines

Eric's PHQ-9 Score

Treatment Options

American Psychiatric Association (APA) Guidelines for Treatment of MDD

1-2 weeks: Improvement from pharmacologic therapy can be seen as early as 1-2 weeks after starting treatment

2-4 weeks: Some patients may achieve improvement in 2-4 weeks

4-6 weeks: Short-term efficacy trials show antidepressant therapy appears to require 4-6 weeks to achieve maximum therapeutic effects

4-8 weeks: The APA recommends 4-8 weeks of adequate* treatment is needed before concluding that a patient is partially responsive or unresponsive to treatment *Adequate dose and duration Practice Guideline for the Treatment of Patients With Major Depressive Disorder. 3rd ed. American Psychiatric Association; 2010.

*Adequate dose and duration

Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 3rd ed. American Psychiatric Association; 2010.

Quiz #4: Treatment Initiation and Monitoring

Assessing for treatment challenges.

Treatment Challenges

Eric's Updated PHQ-9 Score

Possible Challenges to Antidepressant Therapy

Suboptimal efficacy due to the wrong dose, inadequate length of time on the medication, or the person's individual biology not being responsive to the medication
Unpleasant side effects of antidepressants can occur, such as weight gain, insomnia, and sexual dysfunction
Nonadherence to the antidepressant
As a reminder, the American Psychiatric Association (APA) recommends 4-8 weeks of adequate* treatment is needed before concluding that a patient is partially responsive or unresponsive to treatment

Practice Guideline for the Treatment of Patients With Major Depressive Disorder. 3rd ed. American Psychiatric Association; 2010.

MDD Diagnosis

Clinical Probes

Treatment Assessment

Monitoring Considerations

Factors to Consider When Making a MDD Diagnosis

Take a thorough patient history
Previous or current depressive episodes
Previous or current manic or hypomanic episodes
Family history of MDD, bipolar disorder
Medical comorbidities
Consider a broad differential diagnosis

Clinical Queries That Aid in Diagnosing Major Depressive Episodes


DSM-5 Criteria	Clinical Queries
1. Depressed mood most of the day, nearly every day	1. Have you been experiencing persistent feelings of low mood, sadness, or hopelessness?
2. Markedly diminished interest or pleasure in activities most of the day, nearly every day	2. Have you noticed a decrease in interest or pleasure in activities that you once enjoyed?
3. Significant change in weight or appetite	3. Have your eating habits changed, either with a decrease or increase in appetite?
4. Insomnia or hypersomnia	4. Have you noticed and changes in your sleep patterns?
5. Psychomotor agitation or retardation	5. Have you felt unusually restless or fidgety, or slower than usual in your movements or speech?
6. Fatigue or loss of energy	6. Have you been feeling more tired and consistently low on energy?
7. Feelings of worthlessness or excessive or inappropriate guilt	7. Have you been struggling with feelings of low self-worth?
8. Diminished ability to think or concentrate, or indecisiveness	8. Are you finding it difficult to concentrate or think clearly?
9. Recurrent thoughts of death or suicidal ideation	9. Have you been having thoughts about death or harming yourself?

1. Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. American Psychiatric Association; 2013. 2. Kroenke K, et al. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606-613.

APA Practice Guidelines on Treatment Assessment

Wait 4 to 8 weeks to assess treatment response to antidepressants
In patients without adequate response, clinicians can consider changing or augmenting with a second medication
Changes to treatment plans, such as augmenting with a second-generation antipsychotic medication, are reasonable if a patient does not have adequate improvement in 6 weeks
Consistently follow-up with patients to assess treatment effects, adverse medication effects, and risk of self-harm

APA Practice Guidelines note that the frequency of monitoring should be based on:

Symptom severity (including suicidal ideation)
Co-occurring disorders (including general medical conditions)
Treatment adherence
Availability of social supports
Frequency and severity of side effects with medication

Tina Matthews-Hayes is a paid consultant for Abbvie Medical Affairs and was compensated for her time.

American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 3rd ed. American Psychiatric Association; 2010.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders . 5th ed. American Psychiatric Association; 2013.
Kapfhammer HP. Somatic symptoms in depression. Dialogues Clin Neurosci . 2006;8(2):227-239.
Bobo WV. The diagnosis and management of bipolar I and II disorders: clinical practice update. Mayo Clin Proc . 2017;92(10):1532-1551.
Kroenke K, Spitzer RL, Williams JBW. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med . 2001;16:606-613.
Smarr KL, Keefer AL. Measures of depression and depressive symptoms. Arthritis Care Res . 2011;63(S11):S454-S466. doi:10.1002/acr.20556
Rush AJ, Trivedi MH, Ibrahim HM, et al. The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), Clinician Rating (QIDS-C), and Self-Report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry. 2003;54:573-583.
Brown ES, Murray M, Carmody TJ, et al. The Quick Inventory of Depressive Symptomatology–Self-report: a psychometric evaluation in patients with asthma and major depressive disorder. Ann Allergy Asthma Immunol. 2008;100(5):433-438. doi:10.1016/S1081-1206(10)60467-X
Liu R, Wang F, Liu S, et al. Reliability and validity of the Quick Inventory of Depressive Symptomatology-Self-Report Scale in older adults with depressive symptoms. Front Psychiatry . 2021;12:686711. doi:10.3389/fpsyt.2021.686711
Bernstein IH, Rush AJ, Suppes T, et al. A psychometric evaluation of the clinician-rated Quick Inventory of Depressive Symptomatology (QIDS-C16) in patients with bipolar disorder. Int J Methods Psychiatr Res . 2009;18(2):138-146. doi:10.1002/mpr.2855
Bernstein IH, Rush AJ, Trivedi MH, et al. Psychometric properties of the Quick Inventory of Depressive Symptomatology in adolescents. Int J Methods Psychiatr Res. 2010;19(4):185-194. doi:10.1002/mpr.321
Kroenke K. Enhancing the clinical utility of depression screening. CMAJ . 2012;184(3):281-282.doi:10.1503/cmaj.112004
Levinstein MR, Samuels BA. Mechanisms underlying the antidepressant response and treatment resistance. Front Behav Neurosci . 2014;8:208. doi:10.3389/fnbeh.2014.00208
Haddad PM, Talbot PS, Anderson IM, McAllister-Williams RH. Managing inadequate antidepressant response in depressive illness. Br Med Bull. 2015;115(1):183-201. doi:10.1093/bmb/ldv03

This resource is intended for educational purposes only and is intended for US healthcare professionals. Healthcare professionals should use independent medical judgment. All decisions regarding patient care must be handled by a healthcare professional and be made based on the unique needs of each patient.

This is not a diagnostic tool and is not intended to replace a clinical evaluation by a healthcare provider.

Reach out to your family or friends for help if you have thoughts of harming yourself or others, or call the National Suicide Prevention Helpline for information at 800-273-8255.

ABBV-US-00976-MC, V1.0 Approved 12/2023 AbbVie Medical Affairs

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Leanne: A Case Study in Major Depressive Disorder, Recurrent

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Recovery from recurrent depression with mindfulness-based cognitive therapy and antidepressants: a qualitative study with illustrative case studies

Affiliations.

1 Department of Psychiatry, University of Oxford, Oxford, UK.
2 Peninsula Medical School, Faculty of Health, University of Plymouth, Plymouth, UK.
3 Department of Education, University of Oxford, Oxford, UK.
4 Department of Psychiatry, University College London, London, UK.
5 Department of Psychiatry, University of Oxford, Oxford, UK [email protected].
PMID: 32075835
PMCID: PMC7044862
DOI: 10.1136/bmjopen-2019-033892

Objectives: This study aimed to describe the recovery journeys of people with a history of recurrent depression who took part in a psychosocial programme designed to teach skills to prevent depressive relapse (mindfulness-based cognitive therapy (MBCT)), alongside maintenance antidepressant medication (ADM).

Design: A qualitative study embedded within a multicentre, single blind, randomised controlled trial (the PREVENT trial).

Setting: Primary care urban and rural settings in the UK.

Participants: 42 people who participated in the MBCT arm of the parent trial were purposively sampled to represent a range of recovery journeys.

Interventions: MBCT involves eight weekly group sessions, with four refresher sessions offered in the year following the end of the programme. It was adapted to offer bespoke support around ADM tapering and discontinuation.

Methods: Written feedback and structured in-depth interviews were collected in the 2 years after participants undertook MBCT. Data were analysed using thematic analysis and case studies constructed to illustrate the findings.

Results: People with recurrent depression have unique recovery journeys that shape and are shaped by their pharmacological and psychological treatment choices. Their journeys typically include several over-arching themes: (1) beliefs about the causes of depression, both biological and psychosocial; (2) personal agency, including expectations about their role in recovery and treatment; (3) acceptance, both of depression itself and the recovery journey; (4) quality of life; (5) experiences and perspectives on ADM and ADM tapering-discontinuation; and (6) the role of general practitioners, both positive and negative.

Conclusions: People with recurrent depression describe unique, complex recovery journeys shaped by their experiences of depression, treatment and interactions with health professionals. Understanding how several themes coalesce for each individual can both support their recovery and treatment choices as well as health professionals in providing more accessible, collaborative, individualised and empowering care.

Trial registration number: Clinical trial number ISRCTN26666654; post results.

Keywords: antidepressants; depression & mood disorders; psychological therapy.

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Competing interests: None declared.

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Recurrent Brief Mixed Depression

This case study of a 21-year-old woman-referred by a relative because of long-standing severe interpersonal, academic, and occupational impairment-illustrates the importance of screening patients with brief episodes of depression for mixed features.

Jane, who is 21 years old, was referred by her mother because of long-standing severe interpersonal, academic, and occupational impairment. She was euthymic on the day she presented.

Jane had a history of unstable relationships and impulsive, self-destructive behavior. She failed to achieve educational objectives and to maintain stable employment. From early adolescence, she was defiant. When she was 15 years old, her parents became so frustrated with her that they sent her to a residential treatment facility for troubled girls.

In the years before presentation, she abused alcohol and experimented with a number of substances, but had not done so for more than a year before the evaluation. She had 3 first-degree relatives, none of whom were known to have a mood disorder.

Jane had been assessed by mental health professionals, including psychiatrists, over the years. Information about previously rendered diagnoses was not available. She had received psychotherapy but not a somatic treatment.

When interviewed, Jane was asked whether she had ever had episodes of depressed, irritable, or elevated mood, or some combination of these, lasting a week or longer. She did not recall this being the case. She was then asked whether she had ever had 2- to 3-day episodes characterized by some combination of these mood states. She said she had brief episodes of affective disturbance since early adolescence. These episodes occurred every 1 to 2 weeks, lasted about 2 days, and were marked predominantly by depressed and irritable mood. On these days, Jane had particularly low self-esteem, slept about 3 hours more than usual, ate excessively, and had a low level of energy and psychomotor slowing in the morning and restlessness late in the day and at night.

During some of these brief periods of depression, there were times throughout the day when Jane had brief bursts of strangely elevated mood, had hypertalkativeness but not frank pressured speech, was distractible, and had racing and crowded thoughts. She had never had a hypomanic episode or psychotic features. Jane's presentation most closely conformed to the criteria for “recurrent brief depression,” as specified in Appendix B of DSM-IV-TR. She was viewed by her physician as having “recurrent mixed depression.”

Although Jane was euthymic, a decision was made to use a pharmacological intervention aimed at interrupting the cyclical process. She was treated with lamotrigine rather than lithium because of its tolerability. She was instructed to take morning doses as follows: 25 mg for 14 days, then 50 mg for 14 days, followed by 100 mg for 7 days, and then 200 mg thereafter. Jane tolerated the medication well. She had 1- or 2-day periods of mixed depression weekly through the fifth week of treatment. However, from that point onward, she was free of symptoms.

After 9 months of treatment, Jane stopped taking lamotrigine. She became very depressed on the second day. Her mother called Jane's psychiatrist asking for guidance; he recommended that Jane restart her medication, since she had missed only 2 doses. Within a day, she felt well and did not cycle into an episode until 6 months later, when she decided to stop taking the medication. Two days later, Jane was in crisis and her mother called the psychiatrist. He recommended she resume taking lamotrigine. The symptoms remitted within 1 to 2 days. The cyclical process did not recur during the following 2 months, at which point she was lost to follow-up.

Recurrent brief depression is defined as a phenomenon marked by the presence of impairing depressive episodes of at least 2 days’ duration that meet all criteria for MDD (except for the duration criterion) and that occur at least once a month for 12 consecutive months and are not associated with the menstrual cycle. 1-5

Recurrent brief depression was included in Appendix B of DSM-IV and is now included in the main body of DSM-5. Mixed depression was not included in DSM-IV, but it is part of the chapter on MDD in DSM-5.

Mixed depression was first described by Kraepelin, 6 but the concept was ignored until quite recently. 7 The diagnosis of mixed depression, as described in the literature in recent years, focuses on the admixture of subthreshold symptoms of hypomania in the context of DSM-IV–defined MDD. By this standard, Jane did not have mixed depression because she never had an episode lasting at least 2 weeks. However, she did meet the criteria for recurrent brief depression and had significant mixed features during these episodes.

Angst and colleagues 8,9 have proposed validated changes in the criteria for hypomania that apply to this case. Their data suggest that hypomania is reasonably defined without reference to duration and includes symptoms of overactivity, euphoria, or irritability along with any 3 DSM-IV–specified symptoms of hypomania that lead to subjective or social impairment. By this standard, Jane would be viewed as having recurrent brief mixed hypomania.

Jane was euthymic when she presented, yet a psychotropic was prescribed for the purpose of aborting a cyclical process. Lithium would have been a reasonable option. 10 One might have also used divalproex. However, owing to its tolerability, lamotrigine was selected. Jane did well but had symptom relapse within 2 days on both occasions she stopped the medication; with resumption of treatment, she had prolonged asymptomatic periods. This strongly suggests that lamotrigine was causal in interrupting the cyclical process.

This case illustrates the value of assessing patients with histories of stormy interpersonal relationships, impulsive behavior, and low social function for the presence of brief, episodic affective disturbance. It also illustrates the importance of screening patients with brief episodes of depression for mixed features. The use of an antidepressant in an effort to abort the cyclical process might have further destabilized mood and worsened the course of illness.

Disclosures:

Dr Dilsaver is former Professor of Psychiatry and Behavioral Health at the University of Texas, Houston. He is currently at the Imperial County Behavioral Health Services in El Centro, Calif. He is an author of more than 150 publications in the fields of child, adolescent, and adult psychiatry. His focus of attention is the phenomenology of affective illness. He reports no conflicts of interest concerning the subject matter of this case.

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1. Angst J, Merikangas K, Scheidegger P, Wicki W. Recurrent brief depression: a new subtype of affective disorder. J Affect Disord . 1990;19:87-98.

2. Angst J. The history of the concept of recurrent brief depression. Eur Arch Psychiatry Clin Neurosci . 1994;244:171-173.

3. Carta MG, Altamura AC, Hardoy MC, et al. Is recurrent brief depression an expression of mood spectrum disorders in young people? Results of a large community sample. Eur Arch Psychiatry Clin Neurosci. 2003;253:149-153.

4. Pezawas L, Wittchen HU, Pfister H, et al. Recurrent brief depressive disorder reinvestigated: a community sample of adolescents and young adults. Psychol Med . 2003;33: 407-418.

5. LÃ¶vdahl H, Andersson S, Hynnekleiv T, Malt UF. The phenomenology of recurrent brief depression with and without hypomanic features. J Affect Disord. 2009;112:151-164.

6. Kraepelin E. Manic-Depressive Insanity and Paranoia . Edinburgh: E &S Livingstone; 1921.

7. Benazzi F. Bipolar disorder-focus on bipolar II disorder and mixed depression. Lancet . 2007;369:935-945.

8. Angst J, Gamma A, Benazzi F, et al. Toward re-definition of subthreshold bipolarity: epidemiology and proposed criteria for bipolar-II, minor bipolar disorders and hypomania. J Affect Disord . 2003;73:133-146.

9. Angst J, Gamma A. A new bipolar spectrum concept: a brief review. Bipolar Disord. 2002;4(suppl 1):11-14. 10. Conominas A, Bonet P, Nieto E. Recurrent brief depression treated with lithium. Biol Psychiatry . 1998;44:927-929.

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Published: 21 December 2012

A case of cola dependency in a woman with recurrent depression

Charles Boy Kromann 1 &
Connie Thuroee Nielsen 1

BMC Research Notes volume 5 , Article number: 692 ( 2012 ) Cite this article

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Cola is an extremely popular caffeinated soft drink. The media have recently cited a poll in which 16% of the respondents considered themselves to be addicted to cola soft drinks. We find the contrast between the apparent prevalence of cola addiction and the lack of scientific literature on the subject remarkable. To our knowledge, this is the first case of cola dependency described in the scientific literature.

Case presentation

The patient is a 40-year-old woman, who when feeling down used cola to give her an energy boost and feel better about herself. During the past seven years her symptoms increased, and she was prescribed antidepressant medication by her family doctor. Due to worsening of symptoms she was hospitalised and later referred to a specialised outpatient clinic for affective disorders. At entry to the clinic she suffered from constant tiredness, lack of energy, failing concentration, problems falling asleep as well as interrupted sleep. She drank about three litres of cola daily, and she had developed a metabolic syndrome.

The patient fulfilled the ICD-10 criteria for dependency, and on the Yale Food Addiction Scale (YFAS) she scored 40 points. Her clinical mental status was at baseline assessed by the Major Depression Inventory (MDI) = 41, Hamilton Depression - 17 item Scale (HAMD-17) = 14, Young Mania Rating Scale (YMRS) = 2 and the Global Assessment of Functioning (GAF) Scale = 45.

During cognitive therapy sessions she was guided to stop drinking cola and was able to moderate her use to an average daily consumption of 200 ml of cola. Her concentration improved and she felt mentally and physically better. At discharge one year after entry her YFAS was zero. She was mentally stable (MDI =1, HAMD-17 = 0, YMRS = 0 and GAF = 85) and without antidepressant medication. She had lost 7.2 kg, her waistline was reduced by 13 cm and the metabolic syndrome disappeared.

This case serves as an example of how the overconsumption of a caffeinated soft drink likely was causing or accentuating the patient’s symptoms of mental disorder. When diagnosing and treating depression, health professionals should pay attention to potential overuse of cola or other caffeinated beverages.

The mental disorder recurrent depression or depressive episode is in ICD-10 [ 1 ] characterised by the following core symptoms: depressed mood, lack of energy and decreased interest. Accompanying symptoms include decreased appetite, problems with concentration and sleep disturbance [ 1 ]. Untreated, the condition will often result in improper diurnal rhythm, disturbances in eating habits and for some increased use of tobacco [ 2 ], alcohol or other stimulants [ 3 ], e.g. caffeine. This self-medicating behaviour can be seen as both comfort-seeking and as a compensation for lack of energy [ 4 ].

Cola is an extremely popular caffeinated soft drink. Some brands have secret recipes. The most popular brand has a declared sugar content of 106 g/L [ 5 ] and a caffeine concentration of about 100 mg/L [ 6 ]. Lately, the media have presented articles about cola-addicts, and recently one Danish radio station cited a poll in which 16% of 1006 respondents considered themselves to be addicted to cola [ 7 ]. A search on the internet revealed that there was a surprisingly large number of private practice rehab therapists offering their services to cola addicts [ 8 ].

Psychiatric patients often have addictive behaviours, and a study by O’Farrell states that 90% of all hospitalised psychiatric patients show signs of addictive behaviour [ 9 ]. The scientific literature on addictive behaviour related to intake of cola is to our knowledge non-existing. Various searches in the scientific literature as well as more general open literature using PubMed, Google Scholar on “cola” and “dependency” or “addiction” yield no papers on addiction to cola, although some papers on addiction to caffeine mention cola as a caffeine source. Caffeine itself is a well-described substance of abuse and ICD-10 contains definitions for both dependence and withdrawal symptoms [ 1 , 10 ].

It is good clinical practice to consider abuse of alcohol and drugs when treating psychiatric patients, but patients are rarely asked about consumption of soft drinks containing caffeine.

We find the contrast between the belief that cola addiction exists and the apparent lack of scientific literature on the subject interesting and present the case of a 40-year-old woman with recurrent depression, who considered herself addicted to cola and whose daily consumption of cola increased during depressive episodes. To the best of our knowledge, this is the first case of cola dependency described in the scientific literature.

The patient is a 40-year-old woman, who never drank coffee, rarely drank alcohol, but smoked 20 cigarettes per day. She worked as a waitress from the age of 21 years and had unlimited access to cola. During long work shifts she frequently used cola to boost her energy. When she later became a mother, she, as a role model, tried to cut down on cola consumption. However, when she felt down she often used cola to give her an energy boost and thus feel better about herself. Apart from her self-reported addiction to cola and cigarettes she had never used or been addicted to other substances.

The patient had been taking antidepressant medication for seven years. Her family doctor had treated her the first two years with citalopram and with duloxetine, 120 mg, for the last five years. Due to worsening of symptoms (suicidal intentions, lack of energy and sleep disturbances) she was hospitalised for four weeks. She was subsequently discharged with the antidepressant duloxetine, 120 mg, and additional medication (quetiapine, 75 mg and zopiclone, 10 mg) and referred to a specialised outpatient clinic for affective disorders. On admission she still suffered from constant tiredness, lack of energy and failing concentration, and could hardly get her children to school. She had also had a constant feeling of restlessness and difficulties falling asleep, as well as interrupted sleep. Asked about eating habits, she revealed that she drank about three litres of a specific cola brand daily. She had over the years tried other cola brands, but these brands could not give her the same kick of energy feeling. She explained that after a cola intake her tiredness would shortly disappear. Her craving for cola was so pronounced that she fulfilled the ICD-10 criteria for dependency [ 1 ], and on the Danish translation of the Yale Food Addiction-scale (YFAS) [ 11 ] she scored 40 points.

Her clinical mental status was at baseline assessed by the Major Depression Inventory (MDI) =41, Hamilton Depression - 17 item Scale (HAMD-17) =14, Young Mania Rating Scale (YRMS) =2, Global assessment of functioning (GAF) =45 and the physical status by waist circumference =101 cm, weight= 72.9 kg, blood pressure=108/75 mmHg. Laboratory test: Fasting blood glucose: 5.9 mmol/l, HDL: 1.17 mmol/l, triglycerides: 0.75 mmol/l. She fulfilled the criteria for metabolic syndrome according to the International Federation of Diabetes (IDF) [ 12 ].

She was offered cognitive therapy according to the guidelines for recurrent depression. The lack of energy and the feeling of guilt in relation to her parenthood were some of the themes in her case formulation. During sessions she was informed that her excessive consumption of cola could “negatively affect her brain”. She decided to stop drinking cola completely. However, shortly after, she was obsessing over cola and had craving for the soft drink. She was then guided to reduce the consumption and dilute the cola with ice cubes. The following six months she was able to reduce her use to an average daily consumption of 200 ml of cola. During these six months her concentration skills improved, and she felt mentally as well as physically better, so in collaboration with her psychiatrist at the clinic she decided to reduce her psychopharmacological medication.

Treatment outcome

At discharge from the outpatient clinic a year after entry she still had an average daily intake of 200 ml cola but her YFAS-score was now zero. She was not taking any medication and she was mentally stable and assessed by MDI=1, HAM-17=0, YMRS=0, GCI=2 and GAF=85. Due to the reduced consumption of soft drinks she lost weight to 65.7 kg, her waist circumference was reduced to 88 cm, and her blood pressure was approximately the same, 109/77 mmHg. Laboratory test: Fasting blood glucose was reduced to 4.3 mmol/l, HDL: 1.13 mmol/l, triglycerides: 0.78 mmol/l, and she no longer fulfilled the criteria for metabolic syndrome according to IDF.

We have presented a case of cola dependency in a woman with recurrent depression. As part of the treatment for her mental disorder her cola dependency was addressed and treated, with good effect on both her mental and physical health. The fact that her dependence on cola existed ahead of her recurrent depression, and that she could not reduce her consumption of cola by herself, is not sufficient to conclude that her dependence on cola was the primary cause of her recurrent depressions. It is, however, remarkable that both her dependence on cola and her depressive symptoms were reduced simultaneously, when she was treated with a recommended therapeutic method.

Caffeine is the world’s most widely consumed psychoactive substance and has associated psychiatric syndromes such as caffeine-induced sleep disorder, caffeine-induced anxiety disorder and caffeine dependency with withdrawal symptoms that are all well described and documented in the literature [ 13 ].

A daily caffeine intake as low as 100 mg caffeine (1 cup of coffee or one litre of cola may result in caffeine dependency and subsequently withdrawal symptoms such as headaches, drowsiness, dysphoric mood, depression and concentration difficulties [ 13 ].

It is straightforward to consider the patients symptoms solely to be related to caffeine dependency, but several aspects of the case point to a concept of cola dependency separate from the previously described caffeine dependency.

The patient had a distinct preference for a specific band of cola. Although she repeatedly tried, she could not find a satisfactory replacement for her preferred drink, not even among other caffeinated cola-flavoured soft drinks. Caffeine dependency is shown to be associated with taste preferences in the withdrawal phase, but only in acute caffeine abstinence [ 14 ]. The patient slowly reduced her consumption to 200 ml of cola equivalent to 25 mg of caffeine, but was unable to substitute the cola or stop the use completely.

It is very plausible that there is a synergistic effect of caffeine and sugar in drinks, as most energy drinks boast this combination. This effect could add to the addictiveness of cola as sugar is also attributed an addictive potential [ 15 ].

The most interesting aspect of the argumentation for the concept of a separate cola addiction is the common belief in cola dependency among lay people. More than every seventh person in Denmark consider themselves addicted to cola [ 7 ], some to such an extent that they are willing to pay for treatment in order to reduce their consumption.

Whilst the aforementioned poll with self-evaluated dependency is statistically sound, it is probably not scientifically valid. However, the large number of people who consider themselves addicted is still a relevant indication that a potential problem exists.

Cola and other caffeinated soft drinks are not associated with immediate health-threatening effects. They may, however, be related to prolonged and extensive consumption, mainly due to the high sugar content and thus the risk of obesity-related diseases. With regard to dependence on cola there is a discrepancy between the public perception and the official perception among health professionals. This may result in patients having problems with addiction to cola not getting attention in relation to their symptoms, or proper preventive or therapeutic treatment in relation to reduction of their consumption. Individual counseling on this matter could therefore be lacking. This lost opportunity for individual counseling could have negative consequences for patients, who are not reachable through health campaigns.

A case report is no proof of the existence of a specific cola addiction, and more research must be carried out in this field, in order to shed light on the apparent discrepancy between popular belief and the official more reluctant perception among health professionals. Studies examining the potential soft drink addiction are needed.

This case also serves as an example, where the overconsumption of a caffeinated soft drink most probably caused or accentuated the patient’s symptoms of mental disorder. When diagnosing and treating depression, health professionals should pay attention to potential overuse of cola or other caffeinated beverages.

Written and informed consent from the patient was obtained for the publication of this case report.

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Acknowledgements

We would like to thank Nurse Mona Tranberg Henningsen for her great work with data collection.

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CBK conducted the literature review and was a major contributor in the writing of the manuscript. CTN supervised data collection and was a major contributor in the writing of the manuscript. All authors read and approved the final manuscript.

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Major Depressive Disorder, Single And Recurrent Episodes

Major depressive disorder, single episode or recurring, is a severe mental health disorder characterized by severe depressive episodes with persistent sadness, loss of interest in activities once enjoyed, and a significant decrease in daily functioning. Major depressive disorder is a chronic 1 condition, often with recurrent depression, that can substantially impact a person's quality of life, affecting their thoughts, feelings, and ability to perform activities like sleeping, eating, or working.

In the case of a single episode (major depressive disorder single episode) or or a single recurrence, a person experiences one major depressive episode but does not have a history of depression. Contrarily, recurrent major depressive disorder refers to multiple depressive episodes separated by periods of at least two months where the individual was not depressed. Regardless of whether the depression is classified as a single episode or recurrent illness, the severity of the condition can vary, ranging from mild to severe, depending on the number of symptoms 2 present and their impact on the person's life.

Major depressive disorder encompasses a wide range of symptoms that can vary significantly in severity. The signs and symptoms of MDD or recurrent-episode depression generally fall into three main categories: emotional, cognitive, and physical.

These symptoms must last at least two weeks, represent a change from previous functioning, and cause significant distress 3 or impairment in social, occupational, or other vital areas of functioning to be diagnosed as a major depressive episode.

Emotional symptoms

Emotional symptoms of major depression can include the following:

Persistent sadness or emptiness
Irritability or frustration
Loss of interest or pleasure in activities like hobbies, sports, or sex
Feelings of guilt, fixating on past failures, or blaming oneself for what is beyond one’s control
Thoughts of hopelessness or worthlessness

Cognitive symptoms

Cognitive symptoms of major depressive disorder may include the following:

Difficulty concentrating, making decisions, or remembering details
Frequent or recurrent thoughts of death or suicide or suicide attempts
Unexplained physical symptoms, such as back pain or headaches

Physical symptoms

Below are some physical symptoms of major depressive disorder:

Tiredness and lack of energy so that even minor tasks take extra effort
Insomnia or excessive sleeping
Changes in appetite, whether increased or decreased
Weight fluctuations
Slowed movements or speech that is noticeable by others

In the case of recurrent major depressive disorder, the individual experiences these symptoms during multiple depressive episodes, separated by periods of at least two months where they are not depressed.

Major depressive disorder symptoms can appear at any age. However, they commonly first develop in the teenage years or early 20s. If left untreated, episodes may last about six months but can be shorter or significantly longer.

There has not been one specific cause of recurrent episode major depressive disorder. Researchers believe a combination of biological, psychological, and environmental factors are causes for depression.

Biological factors

Potential biological factors in the development of major depressive disorder and recurrent depressive disorder include the following:

Brain chemistry: Neurotransmitters are naturally occurring brain chemicals that may play a role in depression. Changes in the function and effect of these neurotransmitters and how they interact with neural circuits involved in maintaining mood stability may cause depression.
Genetics: MDD is more common in people whose blood relatives also have this mental illness, which suggests a genetic link . However, depression can occur in people without family histories of depression.
Hormones: Changes in the body's balance of hormones, such as during pregnancy, after childbirth, or during menopause, may be involved in causing MDD.

Psychological and environmental factors

Depression may also be caused by environmental and psychological factors, such as the following:

Trauma: Early life trauma, such as childhood abuse, neglect, or the death of a parent, may make a person more vulnerable to developing MDD later in life.
Life changes: Significant life changes, such as losing a job, going through a divorce, or the death of a loved one, may cause a depressive episode.
Chronic illness: Living with a chronic illness can lead to depression, especially if the illness is causing ongoing pain or limiting a person's lifestyle.

These factors may all uniquely interact, so a combination of many factors, rather than any one factor alone, may be responsible for causing MDD. Additionally, substance use and certain medications can contribute to depression.

Treatment 4 for major depressive disorder (MDD) and recurrent major depressive episodes often involves medication, psychotherapy, or a combination of the two, with the primary goal being alleviating symptoms, improving quality of life, and preventing future depressive episodes. In some cases, other treatment options may be utilized if standard treatments are ineffective.

Therapy

Below are a few therapeutic modalities that may be effective in treating depression, whether in a single or multiple episodes:

Cognitive-behavioral therapy (CBT): CBT is often used for treating MDD. This form of therapy helps people with MDD identify negative or unhealthy beliefs and behaviors and replace them with healthy, positive ones. It may also help individuals explore relationships and experiences and develop effective coping strategies.
Interpersonal therapy (IPT): IPT focuses on improving challenges in personal relationships and working through other life changes that may contribute to MDD.
Problem-solving therapy (PST): PST can be beneficial for people living with MDD. This form of therapy helps individuals learn effective ways to manage the adverse effects of stressful life events.

Below are a few medication options that are FDA approved for major depression:

Antidepressants: Antidepressants are often the primary medications used to treat MDD. They include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and atypical antidepressants.
Other Medications: Mood stabilizers , antipsychotics, and other antidepressant medications may also be used when other medications haven't worked adequately.

It can take several weeks to experience the full effect of most of these medications.

It is important to consult with a doctor or medical professional before beginning or changing any medication plan. The information provided in this article is not intended as medical advice; please consult a qualified healthcare professional for personalized guidance.

Other treatment options

Below are a couple of treatment options that might be used for treatment-resistant major depressive disorder:

Electroconvulsive therapy (ECT): The ECT procedure is done under general anesthesia. It involves small electric currents that are passed through the brain, intentionally inciting a brief seizure. ECT seems to cause changes in brain chemistry that may reverse symptoms of certain mental disorders, including MDD.
Transcranial magnetic stimulation (TMS): TMS involves delivering a series of electromagnetic pulses to the brain, which can stimulate nerve cells in the region believed to control mood.

Below are forms of self-care that may be effective in managing daily life with depression alongside evidence-based forms of treatment:

Physical activity and exercise: Regular physical activity can positively impact mood and may be incorporated into a treatment plan.
Nutrition: Eating a balanced diet is essential for physical and mental health.
Adequate sleep: Sleep disturbances often accompany MDD, so improving sleep hygiene may help you manage symptoms.
Mindfulness and stress management techniques: Meditation, yoga, deep breathing, and other stress-reducing activities may help you manage symptoms of MDD.

Treatment plans for MDD or a severe depressive episode can be complex and may require adjustments over time. However, with careful management, the symptoms can be significantly reduced, and individuals can lead healthy, productive lives.

Therapy can be a crucial element in treating major depressive disorder, providing a safe space to explore feelings, thoughts, and behaviors under the guidance of a trained professional. Online therapy, such as that offered by platforms like BetterHelp , can be effective and convenient. These platforms allow individuals to connect with a licensed therapist via phone, video, or text.

Other resources can also provide valuable information and support for MDD patients. The National Institute of Mental Health (NIMH) offers a wealth of information about depression, including symptoms, diagnosis, and treatment. They also have a list of resources for finding help in a crisis or locating a support group.

The Depression and Bipolar Support Alliance (DBSA) offers in-person and online support groups for people with depression or bipolar disorder. These peer-led groups can provide encouragement, understanding, and advice.

The American Psychological Association (APA) and the American Psychiatric Association provide various resources, including tips for finding a suitable mental health professional and insights into the latest research and treatment options. Help is available, and no one has to manage MDD alone. For those with thoughts of suicide, contact 988 Suicide & Crisis Lifeline at 988 . Please also see our Get Help Now page for more immediate resources. For help with substance use, contact SAMHSA’s National Helpline at 1-800-662-HELP (4357). For those experiencing abuse, contact the Domestic Violence Hotline at 1-800-799-SAFE (7233). Support is available 24/7. Please also see our Get Help Now page for more immediate resources.

Please see our Get Help Now page for more immediate resources.

Recent research has further explored the prevalence and management of major depressive disorder (MDD), particularly regarding recurrent episodes. One study published in 2020 in BMC Psychiatry investigated factors associated with recurrence in patients with MDD.

The findings indicated that many patients are at substantial risk of recurring episodes after initial remission, with identified risk factors 5 such as residual symptoms of depression, multiple previous depressive episodes, and a family history of mood disorders. This study underscores the importance of ongoing monitoring and treatment to prevent relapse.

In another study published in Focus , researchers highlighted the potential of neuromodulation therapies , such as transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT), for treating MDD.

The study showed that these therapies could be effective for individuals who don't respond to traditional treatment methods like psychotherapy and medication, demonstrating that MDD can often benefit from flexible, individualized treatment strategies. The authors emphasize that these modalities have improved over time and are associated with fewer side effects than in the past, making them viable options for more patients.

Women are twice as likely to have a depressive episode

Below more key statistics on major depressive disorder (MDD):

According to the National Institute of Mental Health (NIMH), an estimated 17.3 million adults in the United States had at least one major depressive episode. This number represents 7.1% of all US adults.
MDD can often occur alongside anxiety disorders. The Anxiety and Depression Association of America (ADAA) notes that nearly 50% of those diagnosed with depression are also diagnosed with an anxiety disorder .
NIMH reports that among adults with MDD, 65% received combined care by a health professional and medication treatment, indicating a high level of engagement with treatment options.

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Published: 10 August 2024

The incidence and risk factors of perioperative recurrent stroke in elderly patients with previous ischemic stroke receiving hip fracture surgery

Ping Chen 1 na1 ,
Wenhui Zhang 1 na1 ,
Bing Yang 1 ,
Zhirong Fan 1 ,
Yili Chen 1 ,
Xiubing Yu 1 ,
Haiyun Chen 1 &
Haizhou Wang 1

BMC Musculoskeletal Disorders volume 25 , Article number: 636 ( 2024 ) Cite this article

Metrics details

Data are currently lacking regarding perioperative stroke recurrence in hip fracture patients with previous stroke. We aimed to analyze the incidence and risk factors of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery.

We used 2019 and 2020 data from the United States National Inpatient Sample database. We identified elderly patients with previous ischemic stroke who had undergone hip fracture surgery to analyze the incidence of stroke recurrence. A 1:4 propensity score matching was used to balance confounding factors related to demographic data and matched the control group with the stroke recurrence group. Risk factors for stroke recurrence were determined using univariate and multivariate logistic analysis.

The incidence of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery was 5.7% (51/882). Multivariate logistic regression analysis showed that intertrochanteric fracture (odds ratio 2.24, 95% confidence interval 1.14–4.57; p = 0.021), hypertension (odds ratio 2.49, 95% confidence interval 1.26–5.02; p = 0.009), and postoperative pneumonia (odds ratio 4.35, 95% confidence interval 1.59–11.82; p = 0.004) were independently associated with stroke recurrence.

Conclusions

The perioperative stroke recurrence rate in elderly hip fracture patients with previous stroke was 5.7%. Intertrochanteric fracture, hypertension, and postoperative pneumonia were identified as factors significantly associated with stroke recurrence in this study. Adequate systemic support post-fracture, effective blood pressure management, and proactive infection prevention may help reduce stroke recurrence, especially in patients with intertrochanteric fractures.

Peer Review reports

With population aging, hip fractures complicated by stroke have become more common in elderly patients, with a reported incidence ranging between 4% and 15% [ 1 , 2 ]. Hip fractures and stroke can be disabling and potentially fatal, seriously endangering the health and quality of life of elderly patients [ 3 , 4 ]. Stroke is one of the most important risk factors for hip fractures [ 5 ], with ischemic stroke being the most common [ 6 ]. Patients with stroke have an up to four-fold increased risk of hip fractures owing to the high incidence of falls and loss of bone mass on the paretic side [ 7 ].

Previous studies have examined the incidence and risk factors of perioperative stroke in non-cardiac and non-neurologic surgery [ 8 , 9 , 10 , 11 ]. Perioperative stroke is defined as a brain infarction of ischemic or hemorrhagic etiology that occurs during surgery or within 30 days after surgery [ 12 ], with a reported incidence of 0.1–10% [ 13 , 14 ]. It has been well documented that previous stroke can significantly increase the risk of perioperative stroke [ 14 , 15 , 16 ]. However, to our knowledge, no study has specifically addressed the incidence and risk factors associated with recurrent stroke in elderly patients with preoperative stroke who have undergone hip fracture surgery. Relevant data are needed to establish expert consensus or clinical guidelines for elderly patients with hip fracture and preoperative stroke.

In recent years, administrative databases have been widely used in clinical research, and offer the potential to examine infrequent exposures or outcomes. The National Inpatient Sample (NIS) is a comprehensive database containing information on hospital discharge covering both payers and age groups. It accounts for approximately 20% of all admissions to non-federal hospitals in the United States [ 17 ]. In this study, we used the NIS database, aiming to identify elderly patients with preoperative stroke who underwent hip fracture surgery to analyze the incidence and risk factors of perioperative stroke recurrence.

Database and patients

We selected study subjects from the 2019 and 2020 National Inpatient Sample (NIS) databases according to the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes [ 18 , 19 , 20 ]. Patients with preoperative stroke were identified using ICD-10 I63 codes, patients with intraoperative stroke were identified using both ICD-10 G9732 and I97811 codes, and patients with postoperative stroke were identified using both ICD-10 G9752 and I97821 codes. Perioperative stroke is defined as a stroke that occurs either during or after surgery. Therefore, we defined recurrent perioperative stroke as patients with preoperative stroke experienced intraoperative or postoperative stroke. Hip fractures included femoral neck fractures and intertrochanteric fractures, and hip fracture surgeries included primary hip arthroplasty and proximal femoral internal fixation. Specific ICD-10-CM codes involved in this study are provided in Supplementary Material 1 .

There were 99,469 elderly patients with hip fractures who underwent hip fracture surgery, among whom 882 patients had preoperative stroke. Among these 882 patients, 51 experienced perioperative recurrent stroke (Fig. 1 ). To analyze the relationship between perioperative characteristics and stroke recurrence, we performed propensity score matching (PSM) based on patient demographics. We matched 51 cases of stroke recurrence with a control group of patients without stroke recurrence at a 1:4 ratio, with calipers set at 0.05 using the R MatchIt package. Patient demographics and perioperative characteristics before PSM were presented in Supplementary Material 2 . A plot illustrating the balance of covariates before and after PSM was provided in Supplementary Material 3 .

Flowchart of the study population

Included variables

The demographic variables included age, sex, ethnicity, and household income. The hip fracture was classified as either femoral neck or intertrochanteric. The types of surgery included hip replacement and proximal femoral fixation. Previous ischemic stroke was classified into four subtypes as follows: anterior circulation infarction, posterior circulation infarction, cerebellar artery infarction, other or unspecified infarction. Whether long-term use of antithrombotics after stroke was identified using ICD10 Z7901 and Z7902 codes. Elixhauser comorbidities included obesity, alcohol abuse, drug abuse, dementia, depression, acquired immune deficiency syndrome, autoimmune conditions, diabetes, hypertension, chronic heart failure, chronic pulmonary disease, chronic kidney disease, peripheral vascular disease, hypothyroidism, other thyroid disorders, leukemia, lymphoma, metastatic cancer, and solid tumors. The Elixhauser comorbidity score was calculated according to international standards [ 21 ] to evaluate preexisting disease burden. The postoperative complications of interest included deep vein thrombosis, pulmonary embolism, pneumonia, respiratory failure, acute heart failure, myocardial infarction, cardiac dysrhythmias, acute renal failure, urinary tract infection, electrolyte disorders, and sepsis.

Statistical analysis

Missing values in the clinical data were filled in via multiple imputations using the mice package in R. All included variables were subjected to univariate analysis. We evaluated categorical variables using Chi-square or Fisher’s exact tests and non-normal/normal continuous variables using Mann–Whitney U or t - tests. Statistically significant variables in the univariate analysis and clinically relevant variables were entered into the multivariable model. Statistical analysis was performed using R (version 2023.03.1 + 446; The R Foundation for Statistical Computing, Vienna, Austria) software, and statistical significance was set at p < 0.05.

The incidence of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery was 5.7% (51/882). In the univariate analysis, there was no significant difference in demographic data (age, sex, race, and household income) between the stroke recurrence and non-stroke recurrence groups. Regarding fracture type, the stroke recurrence group had a higher proportion of intertrochanteric fractures than the non-stroke recurrence group (68.6% vs. 50%, p = 0.026), whereas the proportion of femoral neck fractures had no significant difference between the two groups. No statistically significant differences were observed between the two groups in surgical type, stroke type, and use of antithrombotics.

With respect to comorbidities, the difference in Elixhauser Score between the two groups was not statistically significant. Only the prevalence of hypertension (51% vs. 34.3%, p = 0.042) in stroke recurrence group was significantly higher than the non-stroke follow-up group. Concerning postoperative complications, the incidence of pneumonia in the recurrent stroke group was significantly higher than that in the non-recurrent stroke group (17.6% vs. 5.9%, p = 0.014), followed by urinary tract infections (33.3% vs. 22.1%, p = 0.135), acute heart failure (9.8% vs. 4.9%, p = 0.318), sepsis (11.8% vs. 7.4%, p = 0.459), electrolyte disorders (47.1% vs. 45.1%, p = 0.925), and myocardial infarction (11.8% vs. 9.8%, p = 0.877). Univariate analysis on patient demographics and perioperative characteristics after PSM were summarized in Table 1 .

Multivariate logistic regression showed that intertrochanteric fracture (OR 2.24, 95% CI 1.14–4.57; p = 0.021), hypertension (OR 2.49, 95% CI 1.26–5.02; p = 0.009), and postoperative pneumonia (OR 4.35, 95% CI 1.59–11.82; p = 0.004) were significantly associated with perioperative stroke (Table 2 ; Fig. 2 ).

Forest map of multivariate logistic analysis of influencing factors for perioperative recurrent stroke

In this study, we used 2019 and 2020 data from the NIS database to examine the incidence and risk factors of perioperative recurrent stroke in elderly patients with preoperative ischemic stroke undergoing hip fracture surgery. PSM was used to balance confounding factors related to demographic data and matched the control group with the stroke recurrence group. Risk factors for stroke recurrence were determined using univariate and multivariate analyses. The incidence of perioperative stroke recurrence was 5.7%. Our findings indicated that intertrochanteric fractures, hypertension, and postoperative pneumonia were associated with stroke recurrence.

To our knowledge, we are the first to report the incidence of perioperative recurrent stroke in hip fracture patients with previous stroke. Previous study reported that found that patients who experienced a stroke within 30 days before elective non-neurologic and non-cardiac surgery had a higher risk of perioperative recurrent stroke (adjusted OR, 8.02; 95% CI, 6.37–10.10; p < 0.001) compared with patients without previous stroke [ 14 ]. However, data on specific incidence rates are lacking. Christiansen et.al [ 15 ] showed that the incidence of perioperative stroke in patients with preoperative stroke undergoing noncardiac and nonvascular surgery within three months was 9.9%. This result is higher than ours, probably because no subgroup analysis of surgery was performed. Lamo‑Espinosa et al. [ 22 ] reported that the overall incidence of stroke in patients with hip fracture was 6.72%, which is close to our results. However, it is not targeted at the perioperative period and patients with previous stroke. Our study adds further insight into the incidence of perioperative stroke recurrence in hip fracture patients with previous stroke. We reported an incidence rate of 5.7%. With reference to previous studies, the incidence rate is still relatively high. Elderly patients with hip fractures are in a hypercoagulable state due to traumatic stress as well as changes in relation to hemodynamics and composition due to fracture, pain, and blood loss [ 23 ]. Moreover, patients with stroke often have hypertension, diabetes, heart disease, hyperlipidemia, and other medical diseases. When hip fracture coexists with previous stroke, the risk of stroke recurrence increases; therefore, sufficient attention should be paid to prevent recurrent stroke in these patients during the perioperative period.

In this study, we found that intertrochanteric fractures were associated with a 2.2-fold increased risk of recurrent stroke (OR 2.24, 95% CI 1.14–4.57; p = 0.021). Excessive blood loss may be a critical pathophysiological factor underlying the high risk of stroke recurrence in intertrochanteric fractures. It has been reported that extracapsular hip fractures are associated with significantly more preoperative blood loss and transfusions compared to their intracapsular counterparts [ 24 ]. Although proximal femoral nail fixation is minimally invasive technique for treating intertrochanteric fractures, it can cause greater blood loss (up to 2100 mL) than expected [ 25 , 26 ]. Additionally, low albumin level has been identified as a risk factor for stroke following hip fractures [ 22 ]. During a stroke, the autoregulation of cerebral blood flow is impaired, which may take one-to-two weeks, or even longer than a month, to recover [ 27 ]. During this period, the cerebral blood supply relies heavily on the maintenance of cerebral perfusion pressure, which is vulnerable to anesthesia and trauma. Perioperative blood loss in intertrochanteric fractures may cause hemodynamic instability and affect cerebral perfusion, thereby increasing the risk of stroke recurrence. Adequate systemic support might help in reducing the recurrence of stroke.

Stroke patients generally require secondary prevention with antithrombotic drugs. A large proportion of these patients are already receiving antithrombotic therapy before sustaining a hip fracture. However, antithrombotic therapy may be discontinued due to concerns about serious perioperative bleeding and higher transfusion demands associated with intertrochanteric fractures. This discontinuation may be another factor that increases the risk of stroke recurrence. This study found no significant association between long-term use of antithrombotic therapy and stroke recurrence. Unfortunately, the NIS database lacks detailed information on antithrombotic therapy, such as the timing and specific drugs used postoperatively. A previous study has identified the discontinuation of antiplatelet ( P = 0.004) as a significant risk factor for perioperative stroke [ 11 ]. Additionally, evidence suggests that continuing anticoagulant treatment in intertrochanteric fracture patients does not increase perioperative blood loss [ 26 ]. Therefore, for patients with hip fracture and stroke, continuing antithrombotic therapy perioperatively remains critical to prevent stroke recurrence after carefully weighing the risk of bleeding.

The timing of surgery may be another critical factor influencing stroke recurrence. Current guidelines recommend that hip fractures be classified as emergencies [ 28 ], and anticoagulation therapy or manageable medical conditions should not justify delaying surgery [ 29 , 30 ]. However, early surgery may also increase the risk of stroke recurrence and mortality [ 16 ], as cerebrovascular autoregulation may not yet be fully restored post-stroke [ 27 ]. Guidelines suggest that elective surgery for patients with concomitant stroke should be postponed for 3–6 months or longer [ 13 , 14 , 16 ]. Despite these recommendations, there are currently no clear guidelines on whether and when to perform surgical hip repair in patients with acute stroke and hip fracture, and the relevant literature is limited. A 2017 study by Christiansen et al. [ 15 ] analyzed the risk of cardiovascular adverse events and mortality following non-cardiac, non-neurological emergency surgery at different times post-stroke. The study indicated that, compared to early surgery (performed 4–14 days post-stroke, 93 cases), patients who underwent immediate surgery (performed 1–3 days post-stroke, 69 cases) had a significantly lower risk of major adverse cardiovascular events within 30 days ( P = 0.029), with no difference in 30-day all-cause mortality ( P = 0.678). One case report described early closed reduction and internal fixation treatment for an intertrochanteric fracture with hemiplegia 30 days after acute stroke. At the 2-year follow-up, the patient had regained basic functional capacity, the fracture had healed well, and the Harris Hip Score was 75 [ 31 ]. In the absence of consistent guidelines, for patients with acute stroke and intertrochanteric fractures, the risks and benefits should be carefully weighed to develop individualized treatment strategies, including the surgical approach and timing.

Hypertension is an important risk factor for stroke. Consistent with our results, Mashour et al. [ 5 ] found that hypertension was an independent predictor of perioperative stroke (OR 3.8, 95% CI 3.1–4.7). Another study showed that elderly patients with acute ischemic stroke after hip fracture experienced hypertension more frequently (73.3%), which was associated with an increased risk of acute ischemic stroke after hip fracture (OR 2.8, 95% CI 1.6–5.1) [ 32 ]. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) results revealed that pharmaceutical antihypertensive therapies could reduce the risk of stroke in hypertensive individuals with a history of stroke [ 33 ]. A 2018 meta-analysis of eight trials showed that pharmaceutical antihypertensive therapies could reduce the stroke recurrence rate (8.7% vs. 10.1%) [ 34 ]. Regarding blood pressure targets, some studies have shown that intensive blood pressure reduction (systolic blood pressure target, < 110–130 mmHg) in elderly patients with hypertension can reduce the risk of stroke by 33% compared with standard blood pressure reduction (systolic blood pressure target, < 130–150 mmHg) [ 35 ]. Therefore, for patients with stroke and concomitant hypertension, appropriate antihypertensive treatment is necessary to control blood pressure within the ideal range and reduce the incidence of perioperative stroke.

In addition, we found that postoperative pneumonia was associated with stroke recurrence. Several studies have provided evidence that systemic infections may trigger or induce acute stroke [ 36 ]. A recent large prospective study in the United Kingdom found an increase in the risk of stroke in the days following acute upper respiratory or urinary tract infection [ 37 ]. Boehme et al. [ 38 ] reported that sepsis is significantly associated with an increased risk of ischemic stroke (OR 28.4, 95% CI 20.0–40.1) and hemorrhagic stroke (OR 12.1, 95% CI 7.5–19.4) within 15 days. Infection-induced inflammation and thrombosis may be the mechanisms underlying the increased stroke risk. However, the relationship between infections and stroke is bidirectional. Infections can cause strokes; however, strokes also induce immunosuppression, which then increases the risk of infection [ 39 ]. It is estimated that approximately one-third of patients with acute stroke develop pneumonia [ 40 ]. Stroke-induced immunosuppression predisposes patients to opportunistic infections, potentially leading to pneumonia or urinary tract infections and worsened stroke outcomes [ 39 ]. Thus, recognizing the possibility that pneumonia increases the risk of perioperative stroke recurrence and that stroke induces pneumonia is critical.

Therefore, it is crucial to develop targeted prevention strategies based on existing evidence to prevent stroke recurrence. First, patients with hip fractures, especially those with intertrochanteric fractures, should receive comprehensive systemic support when necessary. This may include blood transfusions, albumin infusion, and fluid support to ensure adequate cerebral perfusion. Second, perioperative blood pressure management is essential, particularly for patients with a history of hypertension. Individualized blood pressure targets should be established based on the patient’s specific conditions. Third, proactive infection prevention is necessary, especially for preventing pulmonary infections. Bedridden patients should be regularly repositioned, engaged in appropriate passive activities, and receive chest physiotherapy to facilitate sputum clearance. If an infection occurs, effective antibiotic treatment should be promptly administered.

The strength of this study was its identification of preoperative stroke and perioperative stroke recurrence using ICD-10 coding, which made it possible to report outcomes in relation to perioperative stroke recurrence in elderly patients with hip fracture and preoperative stroke, which have rarely been previously reported. In addition, the NIS database involves a large number of patients and uses a multicenter sampling method, meaning that the data are likely to be representative of common practice across the country. However, this study had some limitations. First, owing to the lack of certain intraoperative and postoperative indicators, we were unable to investigate the effects of anesthesia methods, bleeding volume, intraoperative blood pressure, surgical time, and postoperative anticoagulation therapy on stroke recurrence. Second, the incomplete information on stroke types and the lack of data concerning stroke times meant that the association between preoperative stroke subtypes and stroke recurrence could not be determined. Third, as the timing of pneumonia was not recorded, we were unable to determine if pneumonia is a risk factor for stroke recurrence or is a consequence of stroke itself.

Data availability

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank the joint surgery department of Sun Yat-sen Memorial Hospital of Sun Yat-sen University for their help in obtaining the data from the NIS database.

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Ping Chen and Wenhui Zhang contributed equally to this work.

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Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510120, China

Ping Chen, Wenhui Zhang, Ji Qi, Bing Yang, Zhirong Fan, Yili Chen, Xiubing Yu, Haiyun Chen & Haizhou Wang

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ZWH and CP were responsible for the study conception and design; FZR contributed to data acquisition; YB and CYL supervised the statistical analyses; ZWH interpreted the data; ZWH and QJ drafted the manuscript; YXB, WHZ and CHY critically revised and edited the manuscript; CP and WHZ supervised this study and was responsible for the integrity of the data and the accuracy of the analyses.

Corresponding author

Correspondence to Haizhou Wang .

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Chen, P., Zhang, W., Qi, J. et al. The incidence and risk factors of perioperative recurrent stroke in elderly patients with previous ischemic stroke receiving hip fracture surgery. BMC Musculoskelet Disord 25 , 636 (2024). https://doi.org/10.1186/s12891-024-07753-y

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v.10(2); 2020

Original research

Recovery from recurrent depression with mindfulness-based cognitive therapy and antidepressants: a qualitative study with illustrative case studies, alice tickell.

1 Department of Psychiatry, University of Oxford, Oxford, UK

Richard Byng

2 Peninsula Medical School, Faculty of Health, University of Plymouth, Plymouth, UK

Catherine Crane

Felix gradinger, rachel hayes, james robson.

3 Department of Education, University of Oxford, Oxford, UK

Jessica Cardy

Alice weaver, nicola morant.

4 Department of Psychiatry, University College London, London, UK

Willem Kuyken

Associated data.

bmjopen-2019-033892supp001.pdf

bmjopen-2019-033892supp002.pdf

bmjopen-2019-033892supp003.pdf

bmjopen-2019-033892supp004.pdf

bmjopen-2019-033892supp005.pdf

This study aimed to describe the recovery journeys of people with a history of recurrent depression who took part in a psychosocial programme designed to teach skills to prevent depressive relapse (mindfulness-based cognitive therapy (MBCT)), alongside maintenance antidepressant medication (ADM).

A qualitative study embedded within a multicentre, single blind, randomised controlled trial (the PREVENT trial).

Primary care urban and rural settings in the UK.

Participants

42 people who participated in the MBCT arm of the parent trial were purposively sampled to represent a range of recovery journeys.

Interventions

MBCT involves eight weekly group sessions, with four refresher sessions offered in the year following the end of the programme. It was adapted to offer bespoke support around ADM tapering and discontinuation.

Written feedback and structured in-depth interviews were collected in the 2 years after participants undertook MBCT. Data were analysed using thematic analysis and case studies constructed to illustrate the findings.

People with recurrent depression have unique recovery journeys that shape and are shaped by their pharmacological and psychological treatment choices. Their journeys typically include several over-arching themes: (1) beliefs about the causes of depression, both biological and psychosocial; (2) personal agency, including expectations about their role in recovery and treatment; (3) acceptance, both of depression itself and the recovery journey; (4) quality of life; (5) experiences and perspectives on ADM and ADM tapering-discontinuation; and (6) the role of general practitioners, both positive and negative.

Conclusions

People with recurrent depression describe unique, complex recovery journeys shaped by their experiences of depression, treatment and interactions with health professionals. Understanding how several themes coalesce for each individual can both support their recovery and treatment choices as well as health professionals in providing more accessible, collaborative, individualised and empowering care.

Trial registration number

Clinical trial number ISRCTN26666654 ; post results.

Strengths and limitations of this study

Recurrent depression is a leading cause of disability adjusted life years and antidepressant medication (ADM) is the mainstay approach to treatment; this study is the first to describe people’s experiences of recovery with an ADM alongside a psychosocial approach designed to support recovery (mindfulness-based cognitive therapy (MBCT)).
The sample was relatively large and purposively sampled to illustrate a range of recovery journeys and outcomes.
Participants experiences in the 2 years following MBCT were sampled, using an innovative approach to supporting participants’ to describe the richness of their experiences of recovery and treatment.
The sampling necessarily meant that we did not include people with a history of recurrent depression who had decided against ADM, tapering and discontinuing their ADM and/or a psychological approach.

Depression is a major public health problem. Globally more than 264 million people suffer from depression, and lifetime prevalence rates are estimated to be between 6% and 20%. 1 2 Furthermore, depression can be a relapsing and recurring condition, and on average people who experience one episode of depression have seven or eight episodes over their lifetime. 3 Clinical guidance typically recommends that people with recurrent depression should take maintenance antidepressant medications (ADMs) after remission or engage in preventive psychological interventions to maintain recovery. 4 For people with recurrent depression, their recovery journey is shaped by their experiences of depression, ‘illness model’, interactions with mental health professionals, treatments that have and have not worked and expectations about what recovery will entail. 5 For many, ADMs are an important part of their recovery. Reasons for long-term ADM use include positive experiences of ADMs, fear of relapse, perceived lack of alternatives and concerns about withdrawal effects. 6 On the other hand, people also describe a number of reasons for wanting to discontinue ADMs, including feeling better and wanting to test whether depression has gone away, ambivalence and uncertainty about the role of ADMs in recovery, side effects outweighing benefits, questioning whether the self on ADMs is the ‘real self’, and wanting to assert control over their well-being. 7

Research and clinical guidelines suggests that psychological therapies, such as mindfulness-based cognitive therapy (MBCT) and cognitive-behavioural therapy (CBT), can support recovery from depression as well as support discontinuing ADMs. 4 8–10 A significant proportion of people express a preference for psychological therapies, so they can learn strategies that support recovery without the need for long-term reliance on ADMs. 11 But psychological therapies can be difficult to access, involve significant investment of time and energy and are not effective for everyone. 12

While studies have examined people’s experiences of ADM and MBCT in recovery, none have focused primarily on how they operate alongside one another. This study explores how people with a history of recurrent depression describe their experience of using MBCT and ADM to support their recovery, drawing on both written feedback booklets and more in-depth interviews. It was embedded within a randomised controlled trial (RCT) comparing MBCT with support to taper and discontinue ADMs (henceforth MBCT-TS) and maintenance antidepressants over a 2-year period. 13 These findings could inform decision-making between general practitioners (GPs) and patients about the journey of management and recovery from recurrent depression.

Study context

This qualitative process evaluation was embedded within a randomized controlled trial comparing mindfulness-based cognitive therapy with maintenance anti-depressant treatment in the prevention of depressive relapse/recurrence (the PREVENT trial). This was a multicentre, single blind, parallel RCT, which investigated whether MBCT-TS (n=212) was superior to maintenance ADMs (n=212) for the prevention of depressive relapse or recurrence over 24 months (trial design is described by Kuyken et al ). 13–16 The trial found that MBCT-TS was not superior to maintenance ADM in preventing depressive relapse over 2 years; however, a subsequent individual patient data meta-analysis which included this data suggests MBCT as an alternative to maintenance ADMs. 8 We present a statement concerning reflexivity in the online supplementary materials, which outlines the experience and background of the authors, to acknowledge our theoretical positions and values in relation to this study (see online supplementary 1 ). 17 We also include the consolidated criteria for reporting qualitative research (COREQ) checklist to match our procedures against standard criteria for qualitative research (see online supplementary 2 ).

Supplementary data

Participants in the PREVENT trial were recruited from 95 general practices in urban and rural settings in four UK centres, in addition to self-referral. 13 Inclusion criteria were a diagnosis of recurrent major depressive disorder in full or partial remission according to the Diagnostic and Statistical Manual of Mental Disorders-IV 18 ; three or more previous major depressive episodes; age 18 years or older; and on a therapeutic dose of maintenance antidepressant drugs in line with the British National Formulary and NICE (National Institute for Health and Care Excellence) guidance. 4 Exclusion criteria were a current major depressive episode, comorbid diagnoses of current substance misuse; organic brain damage; current or past psychosis, including bipolar disorder; persistent antisocial behaviour; persistent self-injury needing clinical management or therapy; and formal concurrent psychotherapy. All participants gave informed consent before participating in the trial. The full process of recruitment for the PREVENT trial is described in Kuyken et al. 16

This study examined a sub-group of participants from the PREVENT trial (n=42) allocated to the MBCT-TS arm of the trial. Of the 212 participants allocated to receive MBCT-TS, 176 received an adequate dose of treatment (attended four or more group sessions of therapy). 13 The researchers purposively sampled a sub-group of these participants (n=46) to represent a spread of characteristics and experiences with respect to: whether they reported their childhood as having higher or lower levels of abuse, treatment response (relapse/no relapse to a major depressive episode), and ADM discontinuation profile across the 24-month follow-up period (discontinued ADMs, discontinued ADMs but subsequently resumed them, tapered ADMs but never fully discontinued, never tapered or discontinued ADMs). 13 Of the 46 people invited to interview, 42 agreed, which comprised the final sample. Of the four who declined, two had moved away from the area, one was not interested in participating and one participant had changed their contact details and could not be reached. Interviewees did not differ in either baseline characteristics or trial outcomes from the broader study sample (see table 1 ).

Characteristics of the sample

	Interviewed (n=42)	All MBCT-TS participants (n=212)
Demographic characteristics
Female (%)	31 (74)	151 (71)
White (%)	42 (100)	210 (99)
Age (in years)
M (SD)	51.88 (10.51)	50 (12)
Range	25–72	22–78
Psychiatric characteristics
Previous episodes
<6 episodes	26 (62)	120 (57)
≥6 episodes	16 (38)	92 (43)
Comorbid mental health diagnoses
1 or more (%)	15 (36)	75 (35)
Treatment preference at baseline
MBCT-TS preference (%)	34 (81)	150 (71)
ADM preference (%)	1 (2)	12 (6)
No preference (%)	7 (17)	50 (24)
Treatment outcome
Relapse
N (%) that relapsed during the follow-up phase	23 (55)	94 (44)
Antidepressant usage during the follow-up phase
Stopped and stayed stopped (%)	13 (31)	67 (32)
Stopped and resumed (%)	9 (21)	57 (27)
Reduced but never stopped (%)	9 (21)	29 (14)
Never stopped or reduced (%)	11 (26)	23 (11)
Residual depression symptoms
BDI score at baseline, M (SD)	15.90 (11.35)	13.8 (12.4)
BDI score at 24-month follow-up, M (SD)	12.39 (12.25)	11.6 (10.9)

ADM, antidepressant medication; BDI, Beck Depression Inventory; MBCT-TS, mindfulness-based cognitive therapy with support to taper and discontinue ADMs.

MBCT-TS intervention

MBCT-TS comprised MBCT delivered in line with the published treatment manual, 19 but adapted to include a greater focus on developing a relapse/recurrence signature and response plan that explicitly included participants’ reduction/discontinuation of ADM (see Kuyken et al 16 for more detail). The programme involved eight 2¼-hour group sessions, normally over consecutive weeks, with up to four refresher sessions offered in the year following the end of the 8-week programme. Researchers encouraged participants in the MBCT-TS arm to taper and discontinue their maintenance ADMs at several points from the middle of the MBCT-TS course onwards, and provided information to GPs and participants about typical tapering/discontinuation regimes and possible withdrawal effects. If participants experienced a relapse/recurrence during the course of the trial, researchers encouraged them to discuss the most appropriate treatment with their GP and made no further requests that they consider tapering/discontinuing their ADMs.

Qualitative data collection

We used both written feedback booklets (collected at two time points, soon after MBCT and then at study end) and interviews (at study end) to gather participants’ more in-depth experiences of recovery. We combined each participant’s interview and written feedback booklet data to form a single account of their experiences. This formed the study’s data corpus.

Written feedback booklets

One month after completing MBCT-TS all trial participants were invited to complete a feedback booklet addressing attitudes towards, and experiences of, taking and reducing antidepressant medication; experiences of taking part in MBCT-TS and MBCT-TS practices; and the impact of MBCT. In addition to the earlier points, participants received a further feedback booklet 24 months later, which asked the same questions as the first booklet but also included questions focused on participants’ experiences in the follow-up period and basic data on the amount and type of mindfulness practice. The booklets are provided in the online supplementary materials (see online supplementary 3 and 4 ).

Interviews were semi-structured and normally conducted face-to-face by trained researchers, approximately 24 months after MBCT-TS. They lasted between 45 min and 1 hour and explored experiences during the follow-up period, with questions addressing times of wellness, early signs of potential depressive relapse and relapses. Questions explored the use and perceived value of mindfulness techniques, use of ADMs and their combination. We tailored interviews to the specific profile of each participant using a ‘timeline’ prepared in advance and amended by the participant at the interview, which summarised each participant’s ADM use, relapses and significant life events, as reported to the research team during the trial. The interview schedule was deliberately broad in focus (see online supplementary 5 ). Interviews were recorded and transcribed for analysis.

Public and patient involvement

The PREVENT trial benefited from the expertise of many people with lived experience of mental health difficulties including a number of members of a locally organised voluntary group called the lived experience group (LEG). The LEG assisted the PREVENT trial at every stage of its development including both the interview schedule and written feedback booklets. There were reviewed and then trialled by several members of the LEG who suggested a number of fundamental changes. A member of the LEG also provided specific training to the research staff on conducting interviews.

Data analyses

We used thematic analysis as our analytic approach. 17 First, we selected eight participants with a range of ADM discontinuation journeys during the trial period: two who had discontinued ADMs and remained ADM-free; two who had discontinued ADMs and subsequently resumed; two who had never tapered or discontinued ADMs; and two who had tapered but never discontinued ADMs. Four researchers (AT, CC, JR and WK) independently analysed the interview transcripts and accompanying 1-month and 24-month feedback booklets for each participant. In this phase, we conducted inductive analysis, with each researcher developing a preliminary coding frame. These frames were then integrated through discussion to remove redundancies and ensure breadth. This collaboratively produced, inductive coding frame was then combined with deductive codes developed from key literature on participant experiences of MBCT, 20 21 and ADM use, 7 22 to establish a working coding frame.

The lead researcher (AT) then analysed the 42 interviews and accompanying booklets against this coding frame, using NVivo V.11 software. AT, CC and JR met at regular intervals to discuss additional emerging codes and arising themes and, if deemed appropriate, integrated these into the coding frame. Midway through coding, AT sought peer feedback on emerging themes from co-authors, at an internal research meeting and at a symposium focused on antidepressant tapering at an international conference (Tickell, 2018). Feedback from these presentations helped clarify which themes were particularly important, and in particular helped the researchers reflect on those that related specifically to participants’ experiences of ADM alongside MBCT-TS. Once the data were fully coded, the researchers reviewed the themes in the light of the core research question. These were discussed with the wider authorship group, whose input was used to reduce redundancy across themes, and highlight their interactions. Peer review of an earlier version of this manuscript also led to further refining the questions and themes. Finally, we identified cases that illustrated the unique stories of recovery and the ways the common themes coalesced in different ways in illustrative case studies.

The thematic analysis yielded six over-arching themes, each with a number of constituent sub-themes. We provide a summary ( table 2 ) and narrative account of each theme and its constituent sub-themes, illustrating these with extracts from participants’ accounts. While each person’s experience of MBCT and ADMs was unique, these themes converged in complex ways within individual case. Five case examples illustrate these different recovery journeys ( box 1 ).

Themes and sub-themes

Theme	Sub-themes



	e

ADM, antidepressant medication; GP, general practitioners.

Case examples

Mandy . Mandy, aged 57, experienced nine episodes of depression, beginning when she was 32. Following the mindfulness-based cognitive therapy with support to taper and discontinue ADMs (MBCT-TS) course Mandy successfully discontinued her antidepressant medication (ADM) treatment. She did not experience a relapse over the 24-month follow-up period .

Mandy recalled how ADMs had helped her to function well. In the past, she had tried tapering, but had always relapsed, so assumed that ADMs would be a part of her life forever. At first, Mandy was nervous, but was willing to try tapering ADMs gradually and with the support of MBCT-TS ( Personal Agency: Control Over Depression ). Mandy’s GP was supportive, but reassured her that it was ultimately her decision ( Interactions with GP: Presence and Support ). During the MBCT-TS course, Mandy said that she learned a different model of depression and developed a better understanding of ‘how the mind works’ ( Beliefs about the Causes of Depression: Learning a Psychological Model ). She felt more confident about tapering, and said that this time it was ‘so easy, knowing that I have been given tools to help me through it if needed’, and found the course ‘totally liberating’ as it gave her the chance to take control of her depression, rather than the other way round ( Personal Agency: Responsibility ). She also found it helpful to learn about the possible symptoms of withdrawal, which included mood swings. Mandy realised that the relapses she had experienced when she had tried to taper her ADMs in the past might have been withdrawal symptoms, as opposed to ‘real relapses’ ( ADM Tapering / Discontinuation: Managing Withdrawal Effects ). At the time of interview, having discontinued ADMs, Mandy still practised what she learned in MBCT-TS and made it part of her daily routine. She accepted that if she ever relapsed, she could use ADMs, but it would only ever be a short-term solution, because she has the MBCT-TS skills as a ‘weapon’ to help her manage ( Acceptance: Self-Care ).

Greta . Greta, aged 72, had experienced three episodes of depression, beginning when she was 33. Following the MBCT-TS course she discontinued her ADMs but then resumed following a deterioration in mood .

Greta was very optimistic about the course because she hated being on ADMs, which gave her unpleasant side effects that interfered with her quality of life ( Personal Agency: Control over Depression ). At first, Greta said the course made an ‘immense difference’ to her, and she described learning how to combat the negative thoughts and feelings she was having ( Beliefs about the Causes of Depression: Learning a Psychological Model ). The programme left Greta feeling ‘so well and positive’ that she decided to taper her ADMs very quickly ( ADM Tapering/Discontinuation: Pace of Reduction ), but began to feel her mood dipping. Greta thought this must be a sign that the programme was not working, because she should not feel depressed ( Acceptance: Perspectives on Relapse ). Greta went to her GP, who did not seem interested in the programme and told her to resume ADMs immediately ( Interactions with GP: Presence and Support ). She was disappointed and felt ‘guilty’ that she was not able to use these new skills to keep herself well ( Personal Agency: Responsibility ). She stopped practising mindfulness, although the programme made her remember to appreciate the high points in her day and experience more joy ( Quality of Life: From Coping to Enjoying Life ).

Annie . Annie, aged 48, had experienced five episodes of depression, beginning when she was 23. Following the MBCT-TS programme, she discontinued her ADMs but then resumed them later .

Annie felt that ADMs had a positive impact on her life, allowing her to cope day-to-day as a full-time carer for her husband who had a disability. At first, she was very reluctant to try discontinuing ADMs because she believed she might have low levels of serotonin ( Beliefs about the Causes of Depression: Neurochemical Disruption ). However, the programme taught her a new model of understanding depression ( Beliefs about the Causes of Depression: Learning a Psychological Model ), which made her feel empowered to practice the psychological techniques ( Personal Agency: Responsibility ). She started to taper off ADMs, but then her mother died and her husband’s health deteriorated, so it was difficult to find time to practice mindfulness. Her GP advised her it was probably not a good time to discontinue ( Interactions with GP: Presence and Support ), so she resumed ADMs. However, Annie still incorporated the mindfulness exercises into her everyday life, which brought her more joy ( Quality of Life: Experiencing Emotions More Fully ). She also recognised that it is not her fault when she felt depressed, given how challenging her life was ( Acceptance: Resolving Shame ). Annie felt that the best way to manage her depression was to combine ADMs with mindfulness practices, which gave her more skills to look after herself during difficult times ( Acceptance: Self-Care ). She felt hopeful that 1 day she would discontinue ADMs, when her life circumstances were more stable.

George . George, aged 37, had experienced ten episodes of depression, beginning when he was 16. Following the MBCT-TS programme he discontinued his ADMs. He experienced a relapse to depression during the 24-month follow-up .

George was very optimistic about trying an alternative to ADMs, because they made him feel like a ‘zombie’. Having experienced substance misuse issues in the past George had the goal of being totally ‘chemical free’. Before the course, George felt he had no control over his depression symptoms, and his mood would deteriorate suddenly without warning ( Personal Agency: Control ). Through practising the mindfulness skills, he described developing more awareness of his emotions and felt he would have the skills to manage them ( Personal Agency: Responsibility ). George said that the best part of taking part in MBCT-TS was meeting other people with depression, which made him feel more accepting of himself ( Acceptance: Resolving Shame ). He felt that ADMs had masked his symptoms, whereas MBCT-TS allowed him to explore the problems in his life that were contributing to depression and work through them to make long-term changes ( Personal Agency: Responsibility ). When George relapsed shortly after discontinuing ADMs, he carried on practising MBCT-TS and said that the skills he learned were enough to pull him out of that period of low mood ( Acceptance: Perspectives on Relapse ).

Claire . Claire, aged 49, had experienced four episodes of depression, beginning when she was 17. Following the MBCT-TS programme, Claire discontinued her ADMs. She relapsed and resumed medication, but subsequently tapered and discontinued again, and was not using ADMs at the time of her follow-up interview .

At first, Claire was very sceptical about the MBCT-TS programme and thought it might all be ‘mumbo jumbo’. However, she was very keen to come off ADMs, so she approached the programme with an open mind and wanted to give it her all ( Personal Agency: Control ). As the course progressed, Claire changed her mind and began to ‘believe more and more that this might help me’. MBCT-TS gave her new ways to cope with her feelings, which shocked her because she ‘had never took control of my depression before’ ( Personal Agency: Responsibility ). She became very excited and tapered off her medication ‘too quickly’ and ‘hit a brick wall in a short amount of time. Went straight back in to a deep depression’ ( ADM Tapering/Discontinuation: Pace of Reduction ). Her doctor was very understanding, and did not push her to do anything, but advised her to go back on ADMs and try to taper off again when she was feeling better ( Interactions with GP: Presence and Support ). He said that she should try tapering them more slowly next time even though she ‘wanted to get off them as soon as possible’. This time, she did ‘exactly as she was told’ and did not experience a relapse ( Interactions with GP: Following Advice ). Claire was very pleased because she said they had always felt that ADMs had ‘suppressed’ her and that the person she was when taking ADMs ‘wasn’t really me’ ( Quality of Life: Experiencing Emotions More Fully ).

Beliefs about the causes and treatment of depression

This over-arching theme describes participants’ beliefs about the causes of depression and how these beliefs influence their treatment decisions. This theme comprises three sub-themes.

Neurochemical disruption

Many participants described entering the study believing that their recurrent depression was due to a neurochemical disruption in their brain, often citing specifically a deficiency or imbalance of the neurotransmitter serotonin. Participants viewed medication as a way to correct this issue and made parallels to biomedical disorders, viewing ADMs as a ‘physiological need’ in the same way that ‘diabetics require insulin’ because ‘there is some chemical missing ’ (2102; Written feedback, Never tapered or discontinued ). For instance, Annie explained that she went on ADMs because her doctor told her that she had lower levels of serotonin than other people (see box 1 ). This belief appeared to influence expectations about psychological therapy, as some participants stated that they did not understand how ‘mindfulness would be able to counteract depression […] if it’s generated by a chemical imbalance’ (1031, Interview, Never tapered or discontinued ). Other people said that they had not given much thought to why they were depressed or how ADMs worked: ‘Happy pills […] I've never really given it a great deal of thought exactly what they do to be honest. […] I just know I don't feel so bad with them’ (2123, Interview, Tapered but never discontinued ).

Learning a psychological model

Participants described how their views on the causes of depression evolved during and following the MBCT-TS programme. Despite some of the initial reservations described earlier, participants described an open mind as key to engaging with the new psychological model, in which their thoughts, behaviours and emotions played a role in depressive relapses and recurrences: ‘in the first sessions […] I switched from being highly sceptical to very interested very quickly’ (1203, Interview, Discontinued ). Some participants articulated a move away from ‘treating depression as a disease, like if you had a toothache, so you took pills’, and were surprised because they ‘hadn’t thought that there was an alternative’ (1069, Interview, Discontinued ). They began to feel confident to discontinue ADMs with the support of psychological therapy. In addition, people described how the programme gave them more awareness of how external factors, such as relationships or financial situations, could trigger or exacerbate depressive relapses and recurrences. On the other hand, some participants found it more difficult to engage in the programme and found themselves ‘rebelling against it’ because they did not have ‘intellectual confidence in the process’ (3105; Written feedback, Never tapered or discontinued ). People described how their initial treatment experiences influenced their attitudes: those who felt that the techniques were helping them to manage depressive relapse/recurrence often endorsed the psychological model. On the other hand, others who experienced deterioration in mood or relapse sometimes reported that they had reconsidered bio-medical explanations, and decided to resume or remain on ADMs: ‘I really thought depression was a psychosomatic problem, but I am not so sure now. I did give it my best shot, using the mindful techniques, but I still fell into the pit of despair […] I feel that my depression is caused by a chemical imbalance in my body which, at present, is only helped by taking medication’ (2200; Written feedback, Tapered but never discontinued ).

Integrating models

Although some participants viewed depression as either biomedical or psychological, many did not see the two models as distinct and found ways to integrate them. For instance, they conceptualised that ‘antidepressants hold onto the chemical in your body ‘cause you’re not making enough of it yourself’, while MBCT-TS allows you to ‘focus your mind onto how to make your own’ (1139, Interview, Never tapered or discontinued ). It seemed that participants who viewed these models as compatible were more open to using ADMs and using psychological techniques as an additional way to support their recovery, rather than viewing them as competing treatments. Furthermore, when participants observed the diversity of other people’s experiences on the programme, some formed the opinion that there are ‘all sorts of depressions’ underpinned by different causes ‘just as there are colds and flu's and viruses’ (3105, Interview, Never tapered or discontinued ). As such, some reasoned that different people would require different treatment decisions to support recovery: ‘My depression is not necessarily the same as other people’s […] The right combination of changing lifestyle, specific therapies, medication whatever else it takes – that seems to be different for different people’ (3109, Interview, Never tapered or discontinued ).

Personal agency

This over-arching theme describes people’s personal agency in their recovery and consequently their treatment choices. People described entering the study fearful about ADM discontinuation, but were hopeful that a psychological programme could support them. During MBCT-TS, people spoke about feeling better able to manage their vulnerability to depressive relapse, by using the skills and techniques they learned on the programme. While these enhanced feelings of personal agency were largely viewed as a positive and increased many people’s confidence to taper and discontinue ADMs, this was not always the case. For some having more responsibility to manage their condition created a sense of unhelpful pressure. This theme comprises two sub-themes.

Control over depression

People described how their treatment choices affected their sense of control over depression. Some felt that taking ADMs provided a sense of control, as it kept their mood on an even keel. However, this sense of control was contingent on taking ADMs, so many participants recalled how before the trial they would not consider discontinuing because they were afraid that depression would return. Through MBCT, some participants described a change in their sense of personal agency in their recovery, describing a shift from being a ‘helpless victim of circumstance’, to having more ‘control of my feelings and my life’ (1123; Written feedback, Tapered but never discontinued ). They reported increased awareness to recognise the early warning signs of depressive relapse and take steps to respond by applying mindfulness or cognitive-behavioural techniques from a ‘toolbox’, including things like meditation, activity scheduling or enlisting social support: ‘Before the trial, I didn’t have the tools to recognise what was happening. […] I didn’t even know I was getting depressed. [Now] if things are difficult I can do something about it’ (1203, Interview, Discontinued ). Learning these new skills reduced many people’s fears about coming off ADMs, because they felt they had the capacity to prevent or contain depressive relapses. For instance, George said that before the course, he would fall into depressive episodes very suddenly and without warning, whereas the skills learned in MBCT-TS gave him more awareness and control to act and prevent relapses before they occurred (see box 1 ).

Responsibility

Participants also articulated that learning how they could have more agency over their thoughts, feelings, and behaviours led to an increased sense of responsibility to manage their well-being. Most participants viewed this as positive, especially if they were able to use the techniques to manage relapse/recurrence. Some people said they preferred MBCT-TS to taking ADMs because it made recovery feel more like a personal achievement: ‘Once I’ve fallen and I realise that I am depressed, I take myself off and say, do 3 or 4 meditations a day. […] Which to me is better than taking a pill, because I know I’ve worked to get myself well’ (2016, Interview; Written feedback, Discontinued ).

However, not all participants viewed having more agency and responsibility over their well-being positively. In particular, some participants described how this made them feel like it was their fault if they relapsed or felt they had to resume ADMs: ‘I feel sad and disappointed that stopping [ADMs] made me feel low again. […] It makes me feel I'm not right in the head compared to others. I also feel annoyed with myself for not utilising MBCT skills learnt better’ (2123; Written feedback, Discontinued and resumed ). Furthermore, a substantial number of participants expressed the challenge of finding the time, motivation or self-discipline to keep up a regular mindfulness practice outside of the group sessions. Therefore, the sense of control did not always feel stable, as it was contingent on finding time to practice and ‘do it religiously, otherwise I would be fearful of it not being enough’ (2102; Written feedback, Never tapered or discontinued ). Some were disappointed when they realised that psychological therapy was not an ‘all-encompassing cure’ (1222, Interview, Discontinued and resumed ) and would involve an active and ongoing process of engagement with the techniques learned.

This over-arching theme describes people’s feelings of acceptance towards their history of recurrent depression and ongoing need to manage risk of relapse and recurrence. People reported feeling a sense of shame around long-term reliance on ADMs before the trial, feeling it labelled them as an ill person even if feeling well. After the trial, people described an increased sense of acceptance regarding their vulnerability to depression and an increased motivation to engage in self-care to support their recovery. This self-management included either ADMs and/or the psychological techniques for different people. This theme comprises three sub-themes.

Resolving shame

Many participants recalled that before the trial they had felt ‘inadequate’ or unable to cope with life compared with other people because of their recurrent depression treating it as a ‘guilty secret’ (1123; Interview, Tapered but never discontinued ). Taking ADMs had helped some people by reducing the symptoms and allowing them to return to feeling like a ‘normal contributing person in society’ (2200; Interview, Tapered but never discontinued ). However, others said that having to take ADMs on an ongoing basis gave them an underlying feeling that they were still ‘not a well person’ (2102; Interviews, Never tapered or discontinued ), even when the symptoms of depression were absent. For these reasons, some people recalled how before the trial, they found it difficult to name their depression, and ‘couldn’t even or wouldn’t even admit to that’ (1031, Interview, Never tapered or discontinued ). Through MBCT-TS, some participants described how they felt able to name their condition as depression for the first time. They discussed how meeting other people in the programme had made them realise that depression was not a negative aspect of their own self-identity, but an aspect of human experience: ‘You realise it is part of the human condition rather than you’ (1128; Interview, Never tapered or discontinued ), and it ‘confirmed that I am a human, worthwhile person’ (2176; Written feedback, Discontinued and resumed ). This led to increased feelings of acceptance towards depression, because participants experienced a shift away from viewing themselves as abnormal, to seeing depression as a more acceptable response to life’s difficulties: ‘Giving yourself credit […] ‘cause at the end of the day […] our human brain is quite a complex thing, isn’t it? […] There’s nothing wrong in feeling like it’ (2140; Interview, Discontinued and resumed ).

Participants described how developing more acceptance towards their condition improved their attitudes towards self-care. They said that accepting their vulnerability to depression allowed them to ‘look at solutions’ and that they finally had ‘consent to actually do something about it’ (1031, Interview, Never tapered or discontinued ). People described how they increasingly accepted that they needed to take care of themselves, and explained how the programme had taught them legitimate ways to do this such as using mindfulness practices: ‘Previously was a mindset […] that I wasn’t allowed to help myself feel better. […] Whereas this felt a way that I could do it without mollycoddling myself’ (1031, Interview, Never tapered or discontinued ). Participants also described how the programme had reframed self-care not as something ‘fluffy’, but as ‘practical’ and a necessary part of their ongoing recovery: ‘It doesn’t make you any less male of course. [Chuckles] Or any less powerful’ (1203, Interview, Discontinued ). In some cases, this new attitude towards self-care caused a shift such that people felt more acceptance towards taking ADMs: ‘I don't feel any more when I take my pill every morning that there's something wrong with me’ as they recognised it was important to do ‘everything in my power to help myself’ (1177, Interview, Tapered but never discontinued ). Some participants also described how originally they had taken ADMs unwillingly, whereas after MBCT-TS they decided to take ADMs as an act of effective self-management: ‘I used to hate taking them [ADMs] I accept [now] it’s all about looking after yourself isn't it?’ (3103; Interview, Discontinued and resumed ).

Perspectives on relapse

One dimension of acceptance was people’s perspectives on mood fluctuations and relapse itself. Some people favoured ADMs as an approach to relapse prevention, because it guaranteed them stability in their mood. For instance, when Greta experienced a deterioration in mood, she interpreted this as a sign that the MBCT-TS programme had been a ‘failure’ and she resumed taking ADMs (see box 1 ). However, this was not always the case, and many people described how participating in MBCT-TS changed their attitude towards relapse/recurrence. In particular, some people felt more able to accept mood fluctuations and even periods of depression. They described approaching them in a different way, ‘thinking it was a phase that one was going through and sort of accepting, okay this is how you're feeling today’ (1159; Interview, Discontinued and resumed ). Some people reported that they no longer wanted to ‘blank out their negative emotions’, and so did not resume ADMs, even if they relapsed: ‘it’s definitely helped me to realise that they [negative emotions] are a part of me as well’ (4057, Interview, Discontinued ).

Quality of life

People reflected on the ways in which treatment choices influenced their quality of life, specifically moving them from a place of coping, to a position where they could enjoy and appreciate their lives. This theme comprises two sub-themes.

Experiencing emotions more fully

On reflecting on their experiences with ADMs, some participants said that while ADMs lessened their low mood, at the same time they ‘dampen all other emotions’, for instance, they could not feel ‘blissfully happy, couldn’t get angry, and in hindsight feel I was sedated’ (4057, Written feedback, Discontinued ). In the context of depression, some people viewed this numbing effect as helpful, and reflected that while ADMs ‘take away the euphoria that you would get when you've done something really, really, really good’, this was ‘a small price to pay really for not having the really dark times’ (2200; Interviews, Tapered but never discontinued ). However, many people thought that this had negatively affected their quality of life, especially in cases where they found it hard to experience positive emotions. This appeared to influence people’s decision to taper or discontinue ADMs, because they said that restoring their emotional range was an important part of their long-term vision of recovery: both George and Claire described this as a key motivator to discontinue their ADMs (see box 1 ). Indeed, people described how their emotional capacity increased after coming off ADMs: ‘I am more alive: my emotions aren't “levelled out” anymore. I can be happy, sad, angry or calm instead of just bland’ (4057, Written feedback, Discontinued ). Despite this, some people found it a bit of a ‘shock’ at first, when faced with ‘very extreme emotions and feelings’ again ( 1212; Feedback booklets, Discontinued ). Therefore, people found it helpful that the programme taught them techniques to help manage this transition: ‘I definitely used mindfulness during coming off the tablets to […] be aware what’s going on inside and […] calm myself down, to have those little islands of tranquillity’ (4057, Written feedback, Discontinued ). On the other hand, some participants said that despite not tapering or discontinuing ADMs, the programme had helped them to cultivate more positive emotions, and appeared to increase their quality of life on ADMs: ‘I suppose the mindfulness in that respect has helped because […] by slowing yourself down you can […] capture some of that […] joy of life that possibly I would have lost’ (2200; Interviews, Tapered but never discontinued ).

From coping to enjoying life

Many people reflected that in their recovery journey they had been grateful for the periods of time where they were simply able to function. However, some participants said that the programme had helped them to move beyond that mind-set, and to develop more well-being and appreciate life: ‘What has changed? I think my outlook on life, I love life, I really do […] People said to me […] before you used to skulk into the room, now you light up the room. […] I do enjoy life now, where I didn’t before’ (2016, Interview, Discontinued ). They valued the fact that the programme had an active focus on positive functioning, and encouraged them to take part in activities that brought happiness and joy into their life. Participants described this as an active process, facilitated by a sense of having more control and autonomy over making positive decisions in their life: ‘I rearranged my life so that the things I do now are things that I enjoy and want to do’ (1203, Interviews, Discontinued) ; ‘ I am now making bigger future plans to make my life better and introducing new ventures’ (1031, Written feedback, Never tapered or discontinued ).

ADM tapering/discontinuation

The study’s focus included people’s experiences of tapering and discontinuing ADMs in the context of the MBCT-TS programme. This theme describes participants’ views of what helped or hindered the process of discontinuation. It comprises two sub-themes.

Reflecting on the right time to engage with different treatments, many participants felt that ADMs were helpful when they first became depressed: ‘they got me out of my initial depression so that I could cope more with just everyday life’ (4007, Interview, Never tapered or discontinued ). However, many did not envisage being on ADMs indefinitely, and they described an increasing need for insight and self-management of depression as time went on. They thought that the MBCT-TS techniques required more effort, but supported a longer-term vision of recovery, to ‘recognise what makes you depressed and to give you a way to cope with your depression throughout your life for the long-term, and a way that you can come off [ADMs]’ (4007, Interview, Never reduced or discontinued ). As illustrated by this quotation, some participants viewed the MBCT-TS skills as part of a longer-term solution to ADM discontinuation, which extended beyond the 2-year follow-up period. Some participants reflected on how they thought the two treatments could be used in combination to support people at different parts of their journey, from depression through to recovery: ‘I think you need that initial boost of antidepressant to perhaps get you back into a more rational level, and then once you’ve reached that, then bring in the MBCT, until you get back then you know, be weaned off. I can see that working very well really’ (1108, Interview, Never reduced or discontinued ).

Participants discussed the pace at which they tapered ADMs, and how they perceived this to have influenced their outcomes. Some people who were worried about coming off ADMs shared that they exercised caution, testing out the psychological techniques for a set period and tapering slowly. They said this was helpful as it gave them time to learn to use the psychological techniques before giving up the support of their ADMs, ‘by doing it slowly, you are learning those skills and you are finding out how you can use it. [Then] you can start dropping it [ADMs] at your own pace’ (1075; Interviews, Discontinued ). In comparison, those who were keen to come off ADMs and were less fearful of the consequences described tapering more quickly. Although the programme had included explicit guidance to taper gradually, participants’ reports suggested that many people had gone against this advice, and were looking for a ‘quick fix’ to ‘get off the pills as quick as possible’ (2131, Interview, Tapered but never discontinued ). However, on reflection many people thought, ‘perhaps that wasn't the answer perhaps the thing ought to be graded on over a longer period’ (2131, Interviews, Tapered but never discontinued ). Some of these participants reflected that in retrospect they should have been more cautious, and tapering too quickly had led to poorer outcomes: ‘I reduced my tablets too quick and paid the price by having to get straight back to the full dose’ (2016, Interview; Written feedback, Discontinued ). However, some people, like Claire, who did not successfully discontinue on their first attempt reported how they had then tried again, tapering more gradually and with more success (see box 1 ).

Managing withdrawal effects

People said that the programme had helped them to cope with withdrawal effects during and after tapering/discontinuing ADMs. They described how the group and the meditation techniques provided ongoing support to manage this period: ‘I used meditation techniques […] tried to treat myself with pleasurable experiences and told myself that this would pass over. […] I had a network of fellow participants and a trustworthy instructor. All of this put me in a position of confidence that it would work this time’ (4057, Written feedback, Discontinued ). In addition, people said that they were better able to differentiate the side effects of ADM withdrawal from a depressive relapse. For instance, Mandy said that in the past, withdrawal effects had been the biggest hindrance to tapering ADMs, because she had always mistaken them for a depressive relapse and resumed her medication. On the programme, she learned how to differentiate between these effects and ‘real relapses’, and said that tapering was relatively ‘easy’ this time around (see box 1 ). Indeed, some people recalled attempting to discontinue ADMs before the trial and their withdrawal symptoms being ‘misdiagnosed’ ‘as recurring depression’, whereas this time they ‘knew what was coming’ (4057, Written feedback, Discontinued ).

Interactions with GP

Participants’ described their interactions with their GPs as being important in their recovery, in both positive and negative ways. This theme comprises two sub-themes.

Presence and support

Participants described having a GP who was easy to access throughout the process of discontinuation as supportive: ‘Knowing that I could ring the doctor and say, “I need to make an appointment, I need to come and see you.” There was always that net underneath me to catch me if I was falling and I couldn't stop it’ (2090, Interview, Discontinued ), whereas some participants said they found it ‘very difficult’ to access their GPs, and so felt ‘unsupported’ (1123, Written feedback, Tapered but never discontinued ). Participants reported a more positive attitude to the programme if their GP had endorsed it, and some said they had only been convinced to take part in the trial because their GPs said they had themselves done a mindfulness course. When GPs encouraged their patients to use the mindfulness practices, this appeared to be associated with better engagement and subsequent success in ADM tapering and discontinuation: ‘I did reach a stage where I went to see my G.P. as the depression was returning. […] We decided that I should try the exercises before trying pills. I did not need to go back on them yet […] My GP is a great help’ (2090, Written feedback, Discontinued ).

Following advice

Participants differed in the extent to which they sought and followed the advice of their GPs. For instance, some participants described that they remained on their ADMs at their GP’s suggestion: ‘My GP would not allow me to come off my antidepressant or reduce it because I had been on them so long term. [I am] relieved but also a bit disappointed’ (1108; Written feedback, Never tapered or discontinued ). This adherence to medical advice seemed to be greater for participants who had more concerns about discontinuation. For instance, Claire, who relapsed the first time that she had attempted tapering and discontinuation, was much more receptive to her GP’s advice the second time around, because she was afraid of relapsing again (see box 1 ). On the other hand, where people were confident that they had learned the skills to self-manage their depression without ADMs, they more often reported that they could manage the process independently, and placed less value on their GP’s advice: ‘I went along to the doctors because I was polite to ask him if I could stop taking it. And he said, “Well yeah maybe in a few months time you can taper it- ease it off a bit.” But really I had decided (laughs) I was going to stop. So I was just there out of politeness’ (1203; Interview, Discontinued ).

Statement of principal findings

This study explored the recovery journeys of people with recurrent depression who followed a programme (MBCT-TS), designed to teach psychological skills to prevent depressive relapse while providing advice to encourage tapering and discontinuation of maintenance ADMs. 13 Thematic analysis suggested people have unique recovery journeys, but tend to be characterised by six common themes. Five illustrative stories are represented in case studies ( box 1 ). The over-arching themes in participants’ accounts were: beliefs about the causes of depression, personal agency, acceptance, quality of life, ADM tapering/discontinuation and interactions with GP ( table 2 ). Together, these findings have the potential to facilitate discussions between clinicians and patients about the depression recovery journey. The findings also provide a starting point for more research into which treatments for recurrent depression, or combination of treatments, work best for whom and when.

Strengths and weaknesses of this study

This study had a number of methodological strengths. We had a relatively large sample and purposively sampled the population for whom this research is relevant—people with a history of recurrent depression, stable on maintenance ADMs who were open to both a psychological and pharmacological approach to recovery. The study’s time frame enabled participants to reflect on their journey with MBCT-TS and ADMs over 2 years. To support participants’ recollection we developed prompts about the course of their depression and ADM use over the 2-year period based on information we had collected as part of the parent RCT.

Alongside these strengths, it is important to consider the context within which the study took place and its implications for interpretation of the findings. First, the trial was pragmatic in that it recruited participants from a particular population. 16 However, it did not include people either unwilling to consider a psychological therapy or unwilling to consider tapering/discontinuing their medication. Second, the parent trial included monitoring participants’ use of ADM, and if people following MBCT-TS were not tapering/discontinuing they were invited to discuss this with their GPs. Some participants reported feeling pressured to discontinue ADMs and it is reasonable to assume that some participants may have made different decisions in a more naturalistic setting. Third, our purposive sampling means this study does not speak to a larger population of people with a history of depression who are not interested in a psychological approach and tapering/discontinuing their ADMs, or indeed prefer not to use ADM. Fourth, the questions in our feedback booklets and interviews had a particular framing, and it is possible that if the questions were framed differently the answers too may have been different. Finally, for pragmatic reasons we did not ask participants’ feedback on the themes as is sometimes done in qualitative research.

Implications of our findings

Several RCTs have demonstrated that psychological therapies such as CBT and MBCT can support ADM discontinuation, 8–10 but to our knowledge, no qualitative studies have examined people’s experiences of this process. This study adds to the body of literature suggesting that people’s journey involves choices among different treatments, shaped by their prior beliefs, expectations, experiences and interactions with their GPs. In both MBCT and CBT people learn new skills to manage depressive symptoms, gaining new perspectives drawn from both the psychological model and peer-to-peer learning, and develop an increased sense of agency concerning ADM discontinuation. 11 20 21 In this study participants described learning attitudes towards self-care that were participatory and empowering, which facilitated a sense of agency around ADM use, tapering and discontinuation. On the other hand, some people’s biological beliefs about depression, positive experiences of ADM, and/or negative experiences of psychological therapies meant they were happy to use ADM as their primary approach to recovery.

People also emphasised the importance of a GP who is accessible and able to provide support that is collaborative, individualised and empowering, with careful monitoring over time. Moreover, they described how GPs had powerfully shared their models of depression, expectations of treatment and treatment choices. The implication for GPs is to provide accessible, collaborative, individualised and empowering care. Moreover GPs should provide people with explanatory models of depression that are bio-psycho-social alongside appropriate pharmacological and psychological treatment choices. Our findings alongside others 21–23 also suggest GPs should not offer an overly simplistic biological model, for example, ‘your serotonin levels are low’, followed by a (repeat) prescription of ADM.

ADMs are currently the mainstay treatment approach to recurrent depression. Kendrick has argued that many people remain on ADMs without clinical need and could benefit from support and guidance on how to discontinue, especially regarding how to deal with initial withdrawal symptoms. 23 Our findings underscore this. Moreover, participants spoke of the importance of feeling that they had acquired from alternative skills in MBCT-TS to support their recovery generally by being able to manage their depression, but also ADM tapering and discontinuation specifically. For example, where life circumstances were challenging some people felt that the time was not right for them to discontinue ADMs; they made an informed decision to continue with their medication. Even so, the majority of participants who remained on ADMs reported that the MBCT-TS treatment had increased their quality of life on ADMs, and improved their confidence in future discontinuation when circumstances were more favourable. Our analysis also outlines participants’ views on the appropriate timing of different treatments, which provide ideas for when it might be an appropriate time to initiate conversations about ADM and MBCT treatment choices.

People described how their expectations of both MBCT and ADM influenced their treatment choices. Although it is widely assumed that positive expectations predict greater benefit in psychological therapy, in our sample both unrealistically positive expectations (eg, expecting MBCT-TS to be an ‘all-encompassing cure-all’) and very negative expectations (having ‘no intellectual confidence in the process’) appeared to act as a barrier to engagement. These findings are consistent with those of Malpass et al 7 and suggest that openly discussing expectations at key junctures is likely to be key in preventing disappointment or disengagement from what is an effortful process of change. Likewise, in line with Maund et al ’s findings, 6 people’s causal models of depression also appeared to influence their expectations and engagement with psychological therapy. Moreover, they were subject to change during and beyond the therapy process, as their experiences either confirmed or disconfirmed their expectations and working model of depression and its treatment. People who suffer from depression frequently endorse biomedical explanations, 24 and this was evident in our sample. A number of people reported that they derived these models from discussions with their GPs as a rationale for taking ADMs. Previous research suggests that conceiving depression as a biomedical illness can absolve people of personal responsibility and thus challenge stereotypes of depression resulting from personal weakness. 7 However, our findings suggest that strongly held biomedical beliefs appeared to increase feelings of dependency on ADMs, and contribute to negative expectations and lack of engagement with psychological therapy. On the other hand, while learning a psychological model of depression empowered people towards more self-management of depression and feelings of mastery over their emotional well-being, in some cases, when people developed a psychological understanding and then went on to relapse, they blamed themselves. In some cases, practical life circumstances also made it very difficult for people to engage in an approach that required time and effort. Together, this suggests that polarised beliefs about the causes of depression can either compromise self-efficacy or promote self-blame. Many participants found it helpful to bridge biomedical and psychological theories, with parallels to a ‘biopsychosocial’ framework, 25 rather than viewing separate theories as competing, which seemed to foster more flexibility, self-compassion and open-mindedness towards trying different treatment options at different times in their journey of managing recurrent depression. This highlights the importance of recognising that a myriad of factors, including genetic vulnerability and challenging social circumstances, can influence depression.

People sometimes describe ADMs as sedating or numbing. 26 In these interviews participants said this could influence their decision-making about ADM use. For example, in the instance of numbing, some people viewed this as helpful as it reduced their feelings of depression, whereas other people said that ADMs numbed all of their emotions, including positive feelings, and this contributed towards a desire to discontinue them. These findings add to ongoing discussion about the psychoactive effects of ADMs, including their potential benefits and costs, how these effects impact people’s experience of recovery from depression and how participating in psychological therapy can interact with these experiences.

Finally, descriptions of the role of the GP in supporting ADM discontinuation varied markedly, and this appeared to result both from differences between patients in their preferred level of guidance and support, and the availability of their GPs to provide this. For example, some people adhered to their GP’s advice although this was in conflict with their own desired approach, some described informing their GP of their intentions as an act of courtesy, and some did not involve their GP at all. In some of these latter cases, participants felt that they would have benefited from more support, but their GP, for a range of reasons, was unable to provide this. People also described needing more understanding and support over time as they took more responsibility for managing their depression. This is in line with findings from Malpass et al , 7 who suggested that people vary in the extent to which they want to be involved in treatment decision-making, and their preferences for involvement are dynamic, not static. Archer has described different ‘modes of reflexivity’ noting the varying degrees to which people act autonomously or rely on endorsement from others. 27 Moreover, recovery meant different things to different people, and overall, the outcome most important to patients appeared to be their day-to-day functioning and quality of life. It is likely that when GPs are able to recognise their patients’ preferred mode of engagement, and complex, dynamic views of recovery and adapt their approach accordingly, this will facilitate patient–GP consultations about ADM and psychological therapies treatment choices.

Unanswered questions and future research

This work adds to the emerging literature on people’s experiences of recovery from depression with ADM and psychological therapies. Applied research asking how patients and health professionals communicate about their respective models of depression, and understand how this affects treatment decisions, compliance, outcomes and a broader conceptualisation of recovery would be valuable. Extending this to the broader population of people who suffer depression would not only provide an interesting and important alternate perspective but also will be important to consider with respect to recovery journeys and treatment choices.

Our work took a qualitative approach. An obvious next question asks how these process variables affect outcomes. That is to say, what works for who, how, when, to affect treatment outcomes? Finally, such research should prioritise the outcome that is most meaningful to patients: their day-to-day functioning and quality of life.

Dissemination declaration

The trial results were disseminated in workshops and via a flyer to all participants who requested this feedback. The findings of this study will be disseminated to relevant audiences through University of Oxford communications.

Supplementary Material

Acknowledgments.

We would like to thank Trish Bartley for her input to mindfulness-based cognitive therapy (MBCT) therapist training and MBCT fidelity checks. We are grateful to members of our trial steering committee (Chris Leach, Richard Moore and Glenys Parry) and data monitoring committee (Paul Ewings, Andy Field and Joanne MacKenzie) for their valuable advice and support during the project. We acknowledge the additional support provided by the Mental Health and Primary Care Research Networks. We also acknowledge the support provided by the Department of Health and local Primary Care Trusts, in meeting the excess treatment and service support costs associated with the trial. Thanks go to the research team, who facilitated wider qualitative work in the trial, including Aaron Causley, Anna Hunt, Pooja Shah, Holly Sugg, Harry Sutton and Matthew Williams. Above all, we are grateful to the participants for their time in taking part in this trial.

Twitter: @WillemKuyken

Contributors: WK, RB and NM were responsible for the PREVENT trial protocol (A randomized controlled trial comparing mindfulness-based cognitive therapy with maintenance anti-depressant treatment in the prevention of depressive relapse/recurrence) and secured the study funding. NM designed the over-arching qualitative process study to elicit service users’ experiences of treatment, with input from RB, FG, RH, JC and WK. Interviews were conducted by FG and AW, supervised by NM. CC, WK, JR and AT developed the analytical strategy and protocol for the study reported here, and AT conducted the bulk of the analysis, with input from other members of the analytical team. AT, CC and WK drafted the manuscript. All other authors read the manuscript, revised it for significant intellectual content and approved the final manuscript. As chief investigator, WK had overall responsibility for the parent trial within which this study was embedded. The University of Exeter held responsibility for the parent trial and this work. WK is guarantor and corresponding author for the study.

Funding: The PREVENT trial was funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (08/56/01) and was published in full in Health Technology Assessment. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, National Health Service or the Department of Health and Social Care. A trial steering committee, data and ethics monitoring committee, the UK Mental Health Research Network, the Primary Care Research Network, and the Comprehensive Local Research Network all provided support to the project. WK, CC and AT are supported by the Wellcome Trust (107496/Z/15/Z). RB received funding from NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula.

Disclaimer: The funders had no role in the design of the study, in the collection, analysis and interpretation of the data, in the writing of the report or in the decision to submit the article for publication. All authors are independent of the funders, had full access to all of the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis.

Competing interests: None declared.

Patient consent for publication: Not required.

Ethics approval: The South West Research Ethics Committee approved the trial (09/H0206/43), which was registered with the International Standard Randomised Controlled Trial Register (ISRCTN26666654) and the Medicines and Healthcare products Regulatory Agency (2009-012428-10).

Provenance and peer review: Not commissioned; externally peer reviewed.

Data availability statement: No data are available. We will not be making the data publicly available due to its highly confidential and identifiable nature.

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Sensory profiles predict symptoms of central sensitization in low back pain: a predictive model research study.

1. Introduction

2. materials and methods, 2.1. study design, 2.2. ethics, 2.3. setting and participants, 2.4. data collection and measurement procedures, 2.5. measurements, 2.5.1. adolescent/adult sensory profile (aasp), 2.5.2. known factors, numeric pain rating scale (nprs), state-trait anxiety inventory (stai-dy1, stai-dy2), becks depression inventory (bdi), pain catastrophizing scale (pcs), 2.5.3. central sensitization inventory (csi), 2.6. data analysis.

Coefficient of determination R 2 = 0.38; standard error = 4.38.
Abbreviations: CSI t−1 = Central Sensitization Inventory score at 12 weeks; SSv. t0 -score = Sensory Sensitive score at baseline; STAI.trait. t0 -score = trait anxiety score at baseline.



Model	0.38	31.15 (2; 103)	−5.84		0.19	4.38
SSv			0.42	0.27	0.00	0.13
STAI.trait			0.53	0.45	<0.001	0.10


Model	0.23	18.79 (1), <0.001	−6.38		0.00 (1.01; 1.14)	1.47
SSv		3.07 (1), 0.04	0.06		1.07 (1.01; 1.14)	0.04
STAI.trait		18.79 (1), <0.001	0.07		1.07 (1.01; 1.14)	0.03

4. Discussion

4.1. clinical implications, 4.2. limitations, 4.3. recommendations, 5. conclusions, supplementary materials, author contributions, institutional review board statement, informed consent statement, data availability statement, acknowledgments, conflicts of interest.

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Click here to enlarge figure

	Baseline
Male (n) (%)	64 (56.1)
Age (yrs.) (SD)	45 (11.1)
Widespread pain (n) (%)	41 (36.0)
Duration of LBP (wks.) (SD)	3.0 (1.5)
Severity of LBP (NPRS) (SD)	6.1 (1.9)
Severity of leg pain (NPRS) (SD)	1.6 (2.3)
Recurrent episodes (n) (%)	81 (71.1)

Variable	Baseline	12 Weeks	Paired Sample t-Test
	Mean (SD)	Mean (SD)	Mean Difference	95%CI	Two-Sided (p)
CSI-A	30.33 (12.40)	27.33 (12.28)	−3.00	1.09; 4.41	<0.001
Sensory Profiles
Low Registration	27.63 (7.18)	27.09 (7.13)	−0.54	−0.65; 0.95	0.71
Sensation Seeking	45.18 (7.40)	45.19 (8.40)	0.01	−0.80; 0.97	0.85
Sensory Sensitive	31.48 (8.07)	31.29 (8.80)	−0.19	−0.96; 0.85	0.90
Sensation Avoiding	31.81 (8.97)	31.08 (8.36)	−0.73	−0.40; 1.40	0.27
NPRS	6.06 (1.95)	1.96 (1.95)	−4.10	3.91; 4.91	<0.001
STAI state	35.67 (11.30)	34.82 (11.50)	−0.85	−0.72; 2.90	0.24
STAI trait	37.96 (10.37)	36.86 (10.84)	−1.07	−0.65; 2.46	0.25
BDI	8.94 (8.47)	6.78 (6.94)	−2.16	1.35; 4.15	<0.001
PCS cat.	10.25 (9.29)	7.52 (9.29)	−2.73	1.17; 4.45	<0.001
PCS hel.	4.05 (4.29)	2.84 (3.99)	−1.21	0.43; 1.91	0.002
PCS rum.	4.33 (3.84)	3.19 (3.79)	−1.14	0.61; 1.98	<0.001
PCS mag.	1.80 (2.11)	1.30 (2.02)	−0.50	3.91; 4.91	<0.001

	R	F-Ratio	B	p	S.E.
LR	0.11	13.22 (1; 104)	0.60	<0.001	0.17
SSk	0.00	0.01 (1; 104)	−0.01	0.93	0.16
SSv	0.22	28.60 (1; 104)	0.71	<0.001	0.13
SA	0.24	31.90 (1; 104)	0.71	<0.001	0.13
Age	0.00	0.09 (1; 104)	0.03	0.76	0.11
Duration	0.00	0.46 (1; 103)	−0.57	0.50	0.83
NPRS	0.00	0.30 (1; 103)	0.34	0.59	0.62
STAI-state	0.26	35.34 (1; 103)	0.55	<0.001	0.09
STAI-trait	0.32	48.08 (1; 104)	0.67	<0.001	0.10
BDI	0.09	10.17 (1; 99)	0.44	0.00	0.14
PCS-cat	0.01	0.80 (1; 101)	0.12	0.37	0.13
PCS-help	0.00	0.04 (1; 102)	0.06	0.84	0.29
PCS-rum	0.00	0.35 (1; 102)	0.18	0.56	0.31
PCS-mag	0.06	6.66 (1; 101)	1.45	<0.001	0.56

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Gräper, P.J.; Scafoglieri, A.; Clark, J.R.; Hallegraeff, J.M. Sensory Profiles Predict Symptoms of Central Sensitization in Low Back Pain: A Predictive Model Research Study. J. Clin. Med. 2024 , 13 , 4677. https://doi.org/10.3390/jcm13164677

Gräper PJ, Scafoglieri A, Clark JR, Hallegraeff JM. Sensory Profiles Predict Symptoms of Central Sensitization in Low Back Pain: A Predictive Model Research Study. Journal of Clinical Medicine . 2024; 13(16):4677. https://doi.org/10.3390/jcm13164677

Gräper, Pieter J., Aldo Scafoglieri, Jacqueline R. Clark, and Joannes M. Hallegraeff. 2024. "Sensory Profiles Predict Symptoms of Central Sensitization in Low Back Pain: A Predictive Model Research Study" Journal of Clinical Medicine 13, no. 16: 4677. https://doi.org/10.3390/jcm13164677

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