Antidepressant Discontinuation Research Articles

Emotion-induced frontal α asymmetry as a candidate predictor of relapse after discontinuation of antidepressant medication

One in three patients relapse after antidepressant discontinuation. Thus, the prevention of relapse after achieving remission is an important component in the long-term management of Major Depressive Disorder (MDD). However, no clinical or other predictors are established. Frontal reactivity to sad mood as measured by fMRI has been reported to relate to relapse independently of antidepressant discontinuation and is an interesting candidate predictor. Patients (n=56) who had remitted from a depressive episode while taking antidepressants underwent EEG recording during a sad mood induction procedure prior to gradually discontinuing their medication. Relapse was assessed over a six-months follow-up period. 35 healthy controls were also tested. Current source density of the EEG power in the α band (8-13Hz) was extracted and alpha-asymmetry was computed by comparing the power across two hemispheres at frontal electrodes (F5 and F6). Sad mood induction was robust across all groups. Reactivity of α-asymmetry to sad mood did not distinguish healthy controls from patients with remitted MDD on medication. However, the 14 (25%) patients who relapsed during the follow-up period after discontinuing medication showed significantly reduced reactivity in α- asymmetry compared to patients who remained well. This EEG signal provided predictive power (69% out-of-sample balanced accuracy and a positive predictive value of 0.75). A simple EEG-based measure of emotional reactivity may have potential to contribute to clinical prediction models of antidepressant discontinuation. Given the very small sample size, this finding must be interpreted with caution and requires replication in a larger study.

Case study: bipolar disorder and catatonia in an adult autistic male with intellectual disability and Phelan-McDermid syndrome (22q13.33 deletion syndrome): psychopharmacological treatment and symptom trajectories

Objectives Individuals with Phelan-McDermid syndrome (PHMDS) appear to be at increased risk of bipolar disorder and catatonia. While previous research indicates that standard pharmacological treatment of both conditions may be effective in individuals with PHMDS, there is limited knowledge concerning treatment when bipolar disorder and catatonia co-occur. Moreover, symptom trajectories during treatment of bipolar disorder and catatonia in this population have been sparsely described. Methods Case study describing treatment choices, sequence of interventions, and treatment outcome using standardised checklists, for co-occurring bipolar disorder and catatonia in an adult autistic man with intellectual disabilities. Results The current patient was initially diagnosed with a depressive disorder and catatonia. Treatment of catatonia appeared to trigger mania, indicating that catatonia was associated with, and possibly secondary to, affective symptomatology. The successful treatment of catatonia required the discontinuation of antidepressants and the introduction of a mood stabilising drug, in addition to standard catatonia treatment. Conclusions The current case demonstrates the importance of considering the treatment of catatonia in the context of co-occurring affective disorder, and vice versa, in individuals with PHMDS. The symptom trajectories and outcomes described add to the current evidence base concerning the treatment of bipolar disorder/catatonia in PHMDS.

Antidepressant discontinuation patterns and characteristics across sociodemographic groups in the United States

BackgroundWhile antidepressants are frequently used, less is known about contemporary discontinuation patterns, especially across different sociodemographic populations. MethodsPatients 16–84 years initiating antidepressants between 2016 and 2019 within a large US health insurer were identified. The association between patient characteristics and time until antidepressant discontinuation was evaluated using adjusted Cox proportional hazard regression. ResultsAcross 1,365,576 patients, mean time to discontinuation was 168.1 days (SD: 223.6). Men were more likely to discontinue than women (HR: 0.94, 95%CI: 0.94–0.94). Younger patients (16–24 years) were more likely to discontinue than older patients. Patients who were non-White (Asian HR: 1.33, 95%CI: 1.31–1.34; Black HR: 1.27, 95%CI: 1.27–1.28; Hispanic HR: 1.34, 95%:CI 1.34–1.35), with evidence of a substance use disorder (HR: 1.31, 95%CI: 1.27–1.35), or taking tricyclic antidepressants (HR:1.26, 95%CI: 1.25–1.27) were more likely to discontinue. LimitationsInformation on reasons for discontinuation was not available, and wide standard deviations for the primary outcome were reported. The results may not be generalized to non-commercially insured beneficiaries. ConclusionsDiscontinuation is common within the first 6 months of treatment but varies across populations, highlighting patients who may benefit from potential intervention.

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

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. 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. Qualitative study using semi-structured interviews via telephone with adult patients in Germany. 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. 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. 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.

The lived experience of withdrawal from Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants: A qualitative interview study

AbstractBackgroundOur knowledge of the broader impacts of antidepressant withdrawal, beyond physical side effects, is limited. Further research is needed to investigate the lived experiences of withdrawal, to aid clinicians on how to guide patients through the process.AimTo explore antidepressant users’ experiences and views on the withdrawal process and how it affected their quality of life across multiple life domains.Design and SettingWe conducted in‐depth qualitative interviews with 20 individuals from the community who had attempted to withdraw from Serotonin Reuptake Inhibitor antidepressants in the past year.MethodSemi‐structured interviews were conducted online. A topic guide was used to ensure consistency across interviews. The interviews were audio‐recorded and transcribed verbatim and analysed using inductive reflexive thematic analysis.ResultsFive themes were generated. The first highlighted the challenges of managing the release from emotional blunting and cognitive suppression following antidepressant discontinuation. The second related to the negative impact of withdrawal on close relationships and social interactions. The third showed that concurrent with negative physical symptoms, there was a positive impact on health (exercise was reported by some as a coping mechanism). The fourth theme focused on support from GPs and families, emphasising the importance of mental health literacy in others. The final theme underscored the importance of gradual and flexible tapering in enabling a manageable withdrawal experience, and the consideration of timing.ConclusionThe lived experience of withdrawal significantly impacts individuals’ well‐being. Participants emphasised that withdrawal is not just about physical side effects but also affects their emotional, cognitive, and social functioning.Patient and Public Involvement (PPI)Eight people attended individual online meetings to share their experiences of antidepressant withdrawal to help inform the study design and recruitment strategy. Insights from these meetings informed the development of the topic guide. Questions about GP involvement, family relationships, and mood and thinking changes were included based on this PPI work. This ensured the inclusion of topics important to antidepressant users and facilitated the researcher's questioning during the interviews.

Changes in substance use and engagement in gaming/gambling in persons with severe mental illness during the COVID-19 pandemic and earthquakes: a community study in two points.

External stressors, such as COVID-19 pandemic and earthquake, can cause an increase in substance use and addictive behavior in persons with severe mental illnesses (SMI). We analyzed the changes and predictors of substance use and addictive behavior in SMI during these double disasters in Croatia. Questionnaires exploring the presence of substance or behavior addiction disorder, mental ill health [Depression Anxiety Stress Scales-21 (DASS-21), Insomnia Severity Index (ISI), Perceived Stress Scale (PSS), Obsessive-Compulsive Inventory-Revised], coping mechanisms, and perceived social support [Multidimensional Scale of Perceived Social Support (MSPSS)] were administered among 90 participants with SMI included in the RECOVER-E study in May/June 2020 (first COVID-19 wave, Zagreb earthquake) and in December 2020/January 2021 (second COVID-19 wave, Petrinja earthquake). In both time points, a major increase was observed in tobacco smoking (25.0%; 28.6%, respectively) predicted by discontinuation of antidepressants and higher DASS-21 score. Increased sedative use was observed (24.4%; 23.8%, respectively) predicted by higher PSS and ISI scores, lower MSPSS scores, antipsychotic discontinuation and not receiving community mental health team (CMHT) service. In persons with SMI during a double disaster special attention needs to be given to reducing mental-ill health and stress, providing social support and continuity of psychiatric care, through medications and CMHTs.

Secure Messaging Intervention in Patients Starting New Antidepressant to Promote Adherence: Pilot Randomized Controlled Trial.

There are a range of effective pharmacological and behavioral treatments for depression. However, approximately one-third of patients discontinue antidepressants within the first month of treatment and 44% discontinue them by the third month of treatment. The major reasons reported for discontinuation were side effect burden, patients experiencing that the medications were not working, and patients wanting to resolve their depression without using medication. This study tested the acceptability, feasibility, and preliminary effectiveness of an SMS messaging intervention designed to improve antidepressant adherence and depression outcomes in veterans. The intervention specifically targeted the key reasons for antidepressant discontinuation. For example, the secure message included reminders that it can take up to 6 weeks for an antidepressant to work, or prompts to call their provider should the side effect burden become significant. This pilot was a 3-armed randomized controlled trial of 53 veterans undergoing depression treatment at the Iowa City Veterans Affairs Health Care System. Veterans starting a new antidepressant were randomized to secure messaging only (SM-Only), secure messaging with coaching (SM+Coach), or attention control (AC) groups. The intervention lasted 12 weeks with follow-up assessments of key outcomes at 6 and 12-weeks. This included a measure of antidepressant adherence, depressive symptom severity, and side effect burden. The 2 active interventions (SM-Only and SM+Coach) demonstrated small to moderate effect sizes (ESs) in improving antidepressant adherence and reducing side effect burden. They did not appear to reduce the depressive symptom burden any more than in the AC arm. Veteran participants in the SM arms demonstrated improved medication adherence from baseline to 12 weeks on the Medication Adherence Rating Scale compared with those in the AC arm, who had a decline in adherence (SM-Only: ES=0.09; P=.19; SM+Coach: ES=0.85; P=.002). Depression scores on the 9-Item Patient Health Questionnaire decreased for all 3 treatment arms, although the decline was slightly larger for the SM-Only (ES=0.32) and the SM+Coach (ES=0.24) arms when compared with the AC arm. The 2 intervention arms indicated a decrease in side effects on the Frequency, Intensity, and Burden of Side Effects Ratings, whereas the side effect burden for the AC arm increased. These differences indicated moderate ES (SM-Only vs AC: ES=0.40; P=.07; SM+Coach: ES=0.54; P=.07). A secure messaging program targeting specific reasons for antidepressant discontinuation had small-to-moderate ES in improving medication adherence. Consistent with prior research, the intervention that included brief synchronic meetings with a coach appeared to have a greater benefit than the SMS-alone intervention. Veterans consistently engaged with the SMS messaging in both treatment arms throughout the study period. They additionally provided feedback on which texts were most helpful, tending to prefer messages providing overall encouragement rather than specific wellness recommendations. ClinicalTrials.gov NCT03930849; https://clinicaltrials.gov/study/NCT03930849.

Impact of sex on antidepressant discontinuation in groups of similar cytochrome P450 phenotypes.

Although there are studies assessing reasons for antidepressant discontinuation, little is known about the impact of sex differences or cytochrome P450 phenotypes. Our objective is to assess discontinuation rates between males and females and whether CYP450 phenotype influences discontinuation. This is a retrospective review of patients previously enrolled in the Right Drug, Right Dose, Right Time: Using Genomic Data to Individualize Treatment database with major depressive disorder. Patients were evaluated for antidepressants trialed between January 1, 2009, and September 30, 2019. Survival analyses with competing risks were used to analyze discontinuation reasons. A Kaplan-Meier estimation method was used to assess the time to discontinuation and discontinuation rates. Analyses were also completed to assess discontinuation between men and women by phenotypic groups. All tests were two-sided, and p-values ≤ .05 were considered statistically significant. There were 620 antidepressant discontinuation events discovered from 1015 antidepressant trials included. Overall, the median time to discontinuation for males was 2.6 years and 1.9 years for females (hazard ratio [HR] 0.97 [95% confidence interval (CI): 0.80, 1.19], p = .77). The risk of discontinuation was not different between males and females in any of the phenotype groups, which was consistent in the multivariable analyses. Concomitant use of medications that inhibited or induced antidepressant metabolism increased the overall risk of discontinuation (HR 1.45, 95% CI [1.06, 1.99], p = .020) in a time-dependent analysis. We did not detect a significant difference in risk of antidepressant discontinuation rates between males and females even when accounting for cytochrome P450 phenotype. Future studies should account for whether medications that inhibit or induce antidepressant metabolism may be a crucial factor in antidepressant discontinuation.

Discontinuation of antidepressant treatment: a retrospective cohort study on more than 20,000 participants

BackgroundFactors influencing antidepressant treatment discontinuation are poorly understood. In the present study, we aimed to estimate the prevalence of antidepressant treatment discontinuation and identify demographic characteristics, psychiatric comorbidities, and specific side effects associated with treatment discontinuation.MethodsWe leveraged data from the Australian Genetics of Depression Study (AGDS; N = 20,941) to perform a retrospective cohort study on antidepressant treatment discontinuation. Participants were eligible if they were over 18 years of age, had taken antidepressants in the past 4 years, and provided informed consent.ResultsAmong the ten antidepressants studied, the highest discontinuation rates were observed for Mirtazapine (57.3%) and Amitriptyline (51.6%). Discontinuation rates were comparable across sexes except for Mirtazapine, for which women were more likely to discontinue. The two most common side effects, reduced sexual function and weight gain, were not associated with increased odds of treatment discontinuation. Anxiety, agitation, suicidal thoughts, vomiting, and rashes were associated with higher odds for treatment discontinuation, as were lifetime diagnoses of PTSD, ADHD, and a higher neuroticism score. Educational attainment showed a negative (protective) association with discontinuation across medications.ConclusionsOur study suggests that not all side effects contribute equally to discontinuation. Common side effects such as reduced sexual function and weight gain may not necessarily increase the risk of treatment discontinuation. Side effects linked to discontinuation can be divided into two groups, psychopathology related and allergy/intolerance.

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

BackgroundAntidepressant 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.MethodsA 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.DiscussionResults 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 registrationClinicalTrials.gov: NCT05051995, first registered September 20, 2021.

Exploring the prevalence of antidepressant medication discontinuation among pregnant veterans.

US female veterans have higher rates of mental health (MH) disorders compared to US civilian females and, consequently, are at risk for poor MH outcomes during pregnancy. This study evaluated the MH burden and identified the prevalence of antidepressant prescription and discontinuation among pregnant veterans (PGVets). The electronic health records (EHR) of PGVets using the US Veterans Administration's (VA) maternity care benefits over a two-year period were retrospectively reviewed. Inclusion criteria for this study were a current MH diagnosis of depression, anxiety, or posttraumatic stress disorder (PTSD) at the onset of pregnancy (n=351). Outcomes examined included antidepressant use prior to pregnancy, the use and discontinuation of antidepressants during pregnancy, and risk factors for discontinuation. PGVets had a high MH burden, as indicated by multiple comorbid diagnoses of unipolar depression, anxiety, and PTSD in 67% of the sample. At the onset of pregnancy, 163 (46%) were treated with an antidepressant. Only 56 (34%) continued using antidepressants through the pregnancy. Self-discontinuation (34%) and VA provider discontinuation (31%) of antidepressants were found. Among PGVets with documented past suicidal behaviors, 90% discontinued their active antidepressants. PGVets with indicators for more severe MH diagnoses were most likely to discontinue. The MH burden of PGVets and high rates of antidepressant discontinuation have implications for engaging this population in a higher level of perinatal monitoring and intervention. The findings suggest that VA providers and veterans would benefit from risks and benefits education regarding antidepressant use during pregnancy as well as the provision of alternative therapies.

Patterns, predictors, and patient-reported reasons for antidepressant discontinuation in the WHO World Mental Health Surveys.

Despite their documented efficacy, substantial proportions of patients discontinue antidepressant medication (ADM) without a doctor's recommendation. The current report integrates data on patient-reported reasons into an investigation of patterns and predictors of ADM discontinuation. Face-to-face interviews with community samples from 13 countries (n = 30 697) in the World Mental Health (WMH) Surveys included n = 1890 respondents who used ADMs within the past 12 months. 10.9% of 12-month ADM users reported discontinuation-based on recommendation of the prescriber while 15.7% discontinued in the absence of prescriber recommendation. The main patient-reported reason for discontinuation was feeling better (46.6%), which was reported by a higher proportion of patients who discontinued within the first 2 weeks of treatment than later. Perceived ineffectiveness (18.5%), predisposing factors (e.g. fear of dependence) (20.0%), and enabling factors (e.g. inability to afford treatment cost) (5.0%) were much less commonly reported reasons. Discontinuation in the absence of prescriber recommendation was associated with low country income level, being employed, and having above average personal income. Age, prior history of psychotropic medication use, and being prescribed treatment from a psychiatrist rather than from a general medical practitioner, in comparison, were associated with a lower probability of this type of discontinuation. However, these predictors varied substantially depending on patient-reported reasons for discontinuation. Dropping out early is not necessarily negative with almost half of individuals noting they felt better. The study underscores the diverse reasons given for dropping out and the need to evaluate how and whether dropping out influences short- or long-term functioning.

The Effects of CYP2C19 Genotype on Proxies of SSRI Antidepressant Response in the UK Biobank.

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used psychopharmaceutical treatment for major depressive disorder (MDD), but individual responses to SSRIs vary greatly. CYP2C19 is a key enzyme involved in the metabolism of several drugs, including SSRIs. Variations in the CYP2C19 gene are associated with differential metabolic activity, and thus differential SSRI exposure; accordingly, the CYP2C19 genotype may affect the therapeutic response and clinical outcomes, though existing evidence of this link is not entirely consistent. Therefore, we analysed data from the UK Biobank, a large, deeply phenotyped prospective study, to investigate the effects of CYP2C19 metaboliser phenotypes on several clinical outcomes derived from primary care records, including multiple measures of antidepressant switching, discontinuation, duration, and side effects. In this dataset, 24,729 individuals were prescribed citalopram, 3012 individuals were prescribed escitalopram, and 12,544 individuals were prescribed sertraline. Consistent with pharmacological expectations, CYP2C19 poor metabolisers on escitalopram were more likely to switch antidepressants, have side effects following first prescription, and be on escitalopram for a shorter duration compared to normal metabolisers. CYP2C19 poor and intermediate metabolisers on citalopram also exhibited increased odds of discontinuation and shorter durations relative to normal metabolisers. Generally, no associations were found between metabolic phenotypes and proxies of response to sertraline. Sensitivity analyses in a depression subgroup and metabolic activity scores corroborated results from the primary analysis. In summary, our findings suggest that CYP2C19 genotypes, and thus metabolic phenotypes, may have utility in determining clinical responses to SSRIs, particularly escitalopram and citalopram, though further investigation of such a relationship is warranted.

A risk identification model for detection of patients at risk of antidepressant discontinuation.

Between 30 and 68% of patients prematurely discontinue their antidepressant treatment, posing significant risks to patient safety and healthcare outcomes. Online healthcare forums have the potential to offer a rich and unique source of data, revealing dimensions of antidepressant discontinuation that may not be captured by conventional data sources. We analyzed 891 patient narratives from the online healthcare forum, "askapatient.com," utilizing content analysis to create PsyRisk-a corpus highlighting the risk factors associated with antidepressant discontinuation. Leveraging PsyRisk, alongside PsyTAR [a publicly available corpus of adverse drug reactions (ADRs) related to antidepressants], we developed a machine learning-driven algorithm for proactive identification of patients at risk of abrupt antidepressant discontinuation. From the analyzed 891 patients, 232 reported antidepressant discontinuation. Among these patients, 92% experienced ADRs, and 72% found these reactions distressful, negatively affecting their daily activities. Approximately 26% of patients perceived the antidepressants as ineffective. Most reported ADRs were physiological (61%, 411/673), followed by cognitive (30%, 197/673), and psychological (28%, 188/673) ADRs. In our study, we employed a nested cross-validation strategy with an outer 5-fold cross-validation for model selection, and an inner 5-fold cross-validation for hyperparameter tuning. The performance of our risk identification algorithm, as assessed through this robust validation technique, yielded an AUC-ROC of 90.77 and an F1-score of 83.33. The most significant contributors to abrupt discontinuation were high perceived distress from ADRs and perceived ineffectiveness of the antidepressants. The risk factors identified and the risk identification algorithm developed in this study have substantial potential for clinical application. They could assist healthcare professionals in identifying and managing patients with depression who are at risk of prematurely discontinuing their antidepressant treatment.

Antidepressant discontinuation and the role of the pharmacist.

Antidepressant discontinuation and the role of the pharmacist.

Health professionals' views on discontinuation of long-term antidepressants: a systematic review and thematic synthesis.

Long-term antidepressant use, much longer than recommended by guidelines, may cause harmful effects and generate unnecessary costs. To investigate health professionals (HPs) views of long-term antidepressant discontinuation and their barriers and facilitators. Systematic review and meta-synthesis. We included studies that used qualitative data collection and had data on HPs perceptions on (dis)continuing AD use. The review searched nine database sources until May 2022. Study quality was assessed using the CASP checklist and the COREQ criteria. A thematic synthesis was performed. Thirteen studies were included in the review. Nine studies were of GPs' perspectives, one study of psychiatrists', and three of a mix of HPs. Barriers and facilitators to discontinuing long-term AD yielded eight themes, ordered chronologically according to the considerations that HPs make when they review a long-term AD: perception of AD use, fears, HP role and responsibility, HPs attitude towards discontinuation, HPs confidence regarding ability to stop AD, perceived patient readiness to stop, support from relatives and support from other HP. Deprescribing long-term AD is a difficult and complex process for HPs. The review found evidence that the barriers far outweigh the facilitators. More education on the lack of evidence for the long-term effect of AD and the risks of long-term use, guidance on managing long-term use, and support for HPs and patients is needed to increase long-term AD discontinuation. Further research from an HP perspective other than GPs is required and should also explore how HPs can be supported in managing discontinuation ADs.

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

BackgroundAntidepressants 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.MethodsTo 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.DiscussionUntil 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 registrationClinicalTrials.gov (NCT05191277), January 13, 2022.

Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use.

Psilocybin is being studied for depression, but little is known about how it interacts with common antidepressants. Limited data suggest that psilocybin's effects may be diminished by serotonergic antidepressants acutely and even after a medication washout period. To learn the extent to which antidepressants may diminish the effects of psilocybin-containing mushrooms both concurrently and after discontinuation of antidepressants. Online retrospective survey of individuals with use of psilocybin mushrooms (1) with an antidepressant and/or (2) within 2 years of discontinuing an antidepressant. Participants who took mushrooms with an antidepressant and either took the same dose pre-antidepressant or took the same dose with other people not on antidepressant reported the strength of drug effects relative to their expectation. Participants who took mushrooms following discontinuation of an antidepressant also reported the presence of weakened effects. In reports (n = 611) of taking mushrooms with an antidepressant, probabilities [95% CI] of weaker than expected drug effects were 0.47 [0.41-0.54] (selective serotonergic reuptake inhibitors, SSRIs), 0.55 [0.44-0.67] (serotonin norepinephrine reuptake inhibitors, SNRIs) and 0.29 [0.2-0.39] (bupropion). Following SSRI/SNRI discontinuation (n = 1,542 reports), the probability of reduced drug effects was not significantly different from the earliest post-discontinuation timepoint (within 1 week) until 3-6 months, probability = 0.3 [0.20-0.46], p = 0.001. A sensitivity analysis found that removing responses involving fluoxetine, which has an especially long half-life, did not significantly alter this result. SSRI/SNRIs appear to weaken psilocybin drug effects relative to a non-serotonergic antidepressant. This dampening effect may last as long as 3 months following antidepressant discontinuation.

An assessment of the reporting of tapering methods in antidepressant discontinuation trials using the TIDieR checklist

BackgroundThe importance of tapering is increasingly recognised when discontinuing antidepressant medication. However, no previous studies have examined the reporting of antidepressant tapering methods in published studies.AimThe aim of this study was to assess the completeness of reporting of antidepressant tapering methods in a published systematic review using the Template for Intervention Description and Replication (TIDieR) checklist.MethodA secondary analysis was conducted of studies included in a Cochrane systematic review that examined the effectiveness of approaches for discontinuing long-term antidepressant use. The completeness of reporting of antidepressant tapering methods in included studies was independently assessed by two researchers using the 12 items from the TIDieR checklist.ResultsTwenty-two studies were included in the analysis. None of the study reports described all checklists items. No study clearly reported what materials had been provided (item 3) or whether tailoring had occurred (item 9). With the exception of providing a name for the intervention or study procedures (item 1), only a minority of studies clearly reported on any of the remaining checklist items.ConclusionThe findings highlight a lack of detailed reporting of antidepressant tapering methods in published trials to date. This needs to be addressed as poor reporting could hinder replication and adaptation of existing interventions, as well as the potential for successful translation of effective tapering interventions into clinical practice.

Antidepressant adherence trajectory before cancer diagnosis and risk of antidepressant discontinuation after cancer diagnosis among middle-aged US adults.

e18890 Background: For middle-aged adults taking antidepressants before cancer diagnosis, concerns exist about drug-drug interactions between antidepressants and antineoplastics. Clinical guidelines recommend detailed assessment of the new cancer survivor's past history of antidepressant use before considering antidepressant discontinuation. We aimed to determine whether, in real-world settings, the risk of antidepressant discontinuation after cancer diagnosis is associated with survivors’ past antidepressant adherence trajectories. Methods: A retrospective cohort of 45 to 64-year old individuals with incident cancer diagnosis (index date) and ≥2 antidepressant fills in the 9 months before index date, IQVIA PharMetrics Plus for Academics claims, 2006-2020. Antidepressant adherence in the 9-month baseline was measured as monthly proportion of days covered (PDC) before tamoxifen initiation. Group-based trajectory modeling (GBTM) was used to identify clusters of survivors with distinct antidepressant adherence trajectories pre-index date i.e., we calculated polynomial functions of monthly PDCs and compared 2 to 6-group finite mixture models to determine which model best fit the data, based on the Bayesian Information Criterion, expert-adjudged parsimony and ≥10% of the sample in each trajectory group. Antidepressant discontinuation after cancer diagnosis was defined as a 45-day gap in antidepressant supply. Survivors were censored at first of either antidepressant discontinuation, loss of enrollment or 1 year post-index date. Cox regression compared the hazard of antidepressant discontinuation by trajectory group, adjusted for demographics, mental disorder and cancer type. Results: We identified 7,293 middle-aged cancer survivors with prior antidepressant use; females 72%, mean age (SD) 56 (7) years. GBTM identified 4 adherence trajectory groups (consistently high, steady increase, declining, and recent start); metastatic cancer being characteristic of the latter 3 groups relative to the consistently high group. Antidepressant discontinuation was lowest in the consistently high group (26% [mean months-to-discontinuation: 9]) and highest in the declining (68% [5]) and recent start (51% [6]) groups, p < .01. Hazard ratios [95% CI] of discontinuation were significantly higher in the declining (2.7 [2.3 – 3.2]), recent start (1.9 [1.7 – 2.0]) and steady increase (1.5 [1.4 – 1.6]) groups, relative to the consistently high group. Conclusions: Middle-aged cancer survivors with past trajectories of consistently high adherence to antidepressants experience lower risk of antidepressant discontinuation after cancer diagnosis in real-world practice. However, concern remains about the unintended health outcomes of relatively higher antidepressant discontinuation among survivors diagnosed with metastatic cancer.