Risk of relapse after antidepressant discontinuation in anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder: systematic review and meta-analysis of relapse prevention trialsBMJ 2017; 358 doi: https://doi.org/10.1136/bmj.j3927 (Published 13 September 2017) Cite this as: BMJ 2017;358:j3927
- Neeltje M Batelaan, psychiatrist and senior researcher1 2,
- Renske C Bosman, junior researcher1,
- Anna Muntingh, psychologist and senior researcher1 2,
- Willemijn D Scholten, psychotherapist and junior researcher1 2,
- Klaas M Huijbregts, psychologist and senior researcher1 2,
- Anton J L M van Balkom, psychiatrist and professor of evidence-based psychiatry1 2
- 1Department of Psychiatry and Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, VU University Medical Center Amsterdam, Amsterdam, Netherlands
- 2GGZ inGeest, Academic Outpatient Department for Anxiety Disorders, Amsterdam, Netherlands
- Correspondence to: N Batelaan
- Accepted 8 August 2017
Objectives To examine the risk of relapse and time to relapse after discontinuation of antidepressants in patients with anxiety disorder who responded to antidepressants, and to explore whether relapse risk is related to type of anxiety disorder, type of antidepressant, mode of discontinuation, duration of treatment and follow-up, comorbidity, and allowance of psychotherapy.
Design Systematic review and meta-analyses of relapse prevention trials.
Data sources PubMed, Cochrane, Embase, and clinical trial registers (from inception to July 2016).
Study selection Eligible studies included patients with anxiety disorder who responded to antidepressants, randomised patients double blind to either continuing antidepressants or switching to placebo, and compared relapse rates or time to relapse.
Data extraction Two independent raters selected studies and extracted data. Random effect models were used to estimate odds ratios for relapse, hazard ratios for time to relapse, and relapse prevalence per group. The effect of various categorical and continuous variables was explored with subgroup analyses and meta-regression analyses respectively. Bias was assessed using the Cochrane tool.
Results The meta-analysis included 28 studies (n=5233) examining relapse with a maximum follow-up of one year. Across studies, risk of bias was considered low. Discontinuation increased the odds of relapse compared with continuing antidepressants (summary odds ratio 3.11, 95% confidence interval 2.48 to 3.89). Subgroup analyses and meta-regression analyses showed no statistical significance. Time to relapse (n=3002) was shorter when antidepressants were discontinued (summary hazard ratio 3.63, 2.58 to 5.10; n=11 studies). Summary relapse prevalences were 36.4% (30.8% to 42.1%; n=28 studies) for the placebo group and 16.4% (12.6% to 20.1%; n=28 studies) for the antidepressant group, but prevalence varied considerably across studies, most likely owing to differences in the length of follow-up. Dropout was higher in the placebo group (summary odds ratio 1.31, 1.06 to 1.63; n=27 studies).
Conclusions Up to one year of follow-up, discontinuation of antidepressant treatment results in higher relapse rates among responders compared with treatment continuation. The lack of evidence after a one year period should not be interpreted as explicit advice to discontinue antidepressants after one year. Given the chronicity of anxiety disorders, treatment should be directed by long term considerations, including relapse prevalence, side effects, and patients’ preferences.
We thank Caroline Planting of the VU University Medical Center library for her help with conducting the literature search and Adriaan Hoogendoorn for his statistical advice.
Contributors: NMB, AM, WDS, KMH, and AJLMvB devised the concept and design of the study. NMB, WDS, and RCB assessed studies for eligibility and extracted the information from all articles. RCB and AM did the analyses, and all authors interpreted the data. NMB and RCB drafted the article, and all authors revised it critically for important intellectual content and approved the version to be published. NMB and AJLMvB are the guarantors.
Funding: No funding/support was received for this work.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Not needed.
Data sharing: No additional data available.
Transparency: The lead authors (the manuscript’s guarantors) affirm that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.