What helps and what hinders antidepressant discontinuation? Qualitative analysis of patients' experiences and expectations.

BACKGROUND: Many patients with depressive disorders use antidepressants longer than clinically indicated. Long-term use of antidepressants is associated with high individual and societal costs. Patients often perceive antidepressant discontinuation as challenging. AIM: To understand patients' expectations about discontinuation, to document their experiences with long-term use and discontinuation, and to identify factors that can help or hinder discontinuation. DESIGN AND SETTING: Qualitative study using semi-structured interviews via telephone with adult patients in Germany. METHOD: We interviewed 32 patients with remitted major depressive disorder and long-term antidepressant use. We analysed transcripts with content analysis aided by MAXQDA to derive thematic categories. RESULTS: Patients expected to eliminate side effects or regain independence after discontinuation. Such positive expectations were perceived as facilitators and motivated patients' wish to discontinue antidepressants. However, patients also had negative expectations such as recurrence or discontinuation symptoms. Patients' negative expectations were often fuelled by previous negative experiences, which persisted despite a wish to stop antidepressants, and hindered discontinuation. Most patients perceived antidepressants as being effective, but experienced side effects and further problems. Patients felt inadequately informed about treatment duration and methods for discontinuation. Further barriers and facilitators included a stable environment, availability of support, and treatment information. CONCLUSION: Patients prefer to discontinue antidepressants within structured frameworks that provide information and support. Identified facilitators and barriers may help optimise appropriate use and discontinuation of antidepressants in routine practice. Promoting functional expectations and specifying individualised approaches to minimise dysfunctional expectations, adapted to patients' previous experiences, appear to be especially important.

Study protocol: combined N-of-1 trials to assess open-label placebo treatment for antidepressant discontinuation symptoms [FAB-study].

BACKGROUND: Antidepressant discontinuation is associated with a broad range of adverse effects. Debilitating discontinuation symptoms can impede the discontinuation process and contribute to unnecessary long-term use of antidepressants. Antidepressant trials reveal large placebo effects, indicating a potential use of open-label placebo (OLP) treatment to facilitate the discontinuation process. We aim to determine the effect of OLP treatment in reducing antidepressant discontinuation symptoms using a series of N-of-1 trials. METHODS: A series of randomized, single-blinded N-of-1 trials will be conducted in 20 patients with fully remitted DSM-V major depressive disorder, experiencing moderate to severe discontinuation symptoms following antidepressant discontinuation. Each N-of-1 trial consists of two cycles, each comprising two-week alternating periods of OLP treatment and of no treatment in a random order, for a total of eight weeks. Our primary outcome will be self-reported discontinuation symptoms rated twice daily via the smartphone application 'StudyU'. Secondary outcomes include expectations about discontinuation symptoms and (depressed) mood. Statistical analyses will be based on a Bayesian multi-level random effects model, reporting posterior estimates of the overall and individual treatment effects. DISCUSSION: Results of this trial will provide insight into the clinical application of OLP in treating antidepressant discontinuation symptoms, potentially offering a new cost-effective therapeutic tool. This trial will also determine the feasibility and applicability of a series of N-of-1 trials in a clinical discontinuation trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05051995, first registered September 20, 2021.

Disentangling pharmacological and expectation effects in antidepressant discontinuation among patients with fully remitted major depressive disorder: study protocol of a randomized, open-hidden discontinuation trial.

BACKGROUND: Antidepressants are established as an evidence-based, guideline-recommended treatment for Major Depressive Disorder. Prescriptions have markedly increased in past decades, with a specific surge in maintenance prescribing. Patients often remain on antidepressants longer than clinically necessary. When attempting to stop, many patients experience adverse discontinuation symptoms. Discontinuation symptoms can be debilitating and hinder successful discontinuation. While discontinuation symptoms can result from pharmacological effects, evidence on nocebo-induced side effects of antidepressant use suggests that patients' expectations may also influence occurrence. METHODS: To disentangle pharmacological and expectation effects in antidepressant discontinuation, patients with fully remitted Major Depressive Disorder who fulfill German guideline recommendations to discontinue will either remain on or discontinue their antidepressant. Participants' expectations will be manipulated by varying verbal instructions using an open-hidden paradigm. Within the open trial arms, participants will receive full information about treatment, i.e., high expectation. Within the hidden trial arms, participants will be informed about a 50% chance of discontinuing versus remaining on their antidepressant, i.e., moderate expectation. A total of N = 196 participants will be randomly assigned to either of the four experimental groups: open discontinuation (OD; n = 49), hidden discontinuation (HD; n = 49), open continuation (OC; n = 49), or hidden continuation (HC; n = 49). Discontinuation symptom load during the 13-week experimental phase will be our primary outcome measure. Secondary outcome measures include discontinuation symptom load during the subsequent 39-week clinical observation phase, recurrence during the 13-week experimental period, recurrence over the course of the complete 52-week trial evaluated in a time-to-event analysis, and stress, anxiety, and participants' attentional and emotional processing at 13 weeks post-baseline. Blood and saliva samples will be taken as objective markers of antidepressant blood serum level and stress. Optional rsfMRI measurements will be scheduled. DISCUSSION: Until today, no study has explored the interplay of pharmacological effects and patients' expectations during antidepressant discontinuation. Disentangling their effects has important implications for understanding mechanisms underlying adverse discontinuation symptoms. Results can inform strategies to manage discontinuation symptoms and optimize expectations in order to help patients and physicians discontinue antidepressants more safely and effectively. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05191277), January 13, 2022.

Associations Between Mental Health Problems in Adolescence and Educational Attainment in Early Adulthood: Results of the German Longitudinal BELLA Study.

Mental health problems (MHP) in adolescence are a major public health concern of the 21st century. Global prevalence estimates range between 10 and 20%. Most MHP manifest by adolescence and persistence rates are high, often accumulating further impairment in early adulthood and beyond. We analyzed data of N = 433 participants from the German longitudinal BELLA study to examine whether MHP in adolescence negatively affect educational attainment in early adulthood. Externalizing and internalizing MHP among adolescents aged 11-17 years were assessed at baseline using the Strengths and Difficulties Questionnaire. Educational attainment was assessed at the 6-year follow-up based on level of education, failure to attain the expected level of education, and dropout from vocational or academic training. Findings from logistic regression analyses suggest that more pronounced externalizing MHP in adolescence predict a lower level of education in early adulthood. We did not find a corresponding effect for internalizing MHP. Adolescents with higher-educated parents were less likely to attain a lower level of education themselves and less likely to fail in attaining their expected level of education. Our findings support that educational attainment presents a central channel for intergenerational reproduction of education and forms an important pathway for upward, but also downward social mobility. The current study emphasizes school as a central setting to implement measures to prevent onset and persistence of MHP and to foster equal opportunities in education.