July 9, 2025

expert reaction to systematic review and meta-analysis on antidepressant withdrawal symptoms

A systematic review and meta-analysis published in JAMA Psychiatry looks at antidepressant withdrawal symptoms. 

Dr Susannah Murphy, Associate Professor, Department of Psychiatry, University of Oxford, said:

“People taking antidepressants are understandably concerned about what might happen when they stop, particularly about the possibility of withdrawal symptoms. This study is an important contribution to the field, providing a comprehensive review of the current evidence on antidepressant discontinuation. Its strengths lie in the large amount of data analysed—over 50 studies representing more than 17,000 patients—and the useful comparison it makes between those stopping antidepressants and those in placebo group.

“The findings suggest that while some individuals may experience symptoms like dizziness, nausea, vertigo, or nervousness, the vast majority do not. This indicates it could be helpful for clinicians to inform patients about these potential effects, while also reassuring them that such symptoms are not common.

“It’s important to note that the studies included only measured discontinuation symptoms in the first two weeks after stopping medication, so we still need more research to understand how long these effects might last.  The study was also not able to assess the severity of the symptoms, and this is important to consider in future studies”

Prof Katharina Domschke, Full Professor of Psychiatry and Chair of the Department of Psychiatry and Psychotherapy, University of Freiburg, Germany, said:

“The methodologically very robustly collected and analyzed data reported in the study by Henssler et al. (Lancet Psychiatry, 2024) is now supported by the present results published in JAMA Psychiatry, showing only small numbers of antidepressant discontinuation symptoms in some cases. 

“The study is characterized by an excellent methodological quality being the most comprehensive meta-analysis on the topic to date including 50 studies, 38 of which had an observation period longer than two weeks, the critical time frame during which discontinuation symptoms are expected to occur. With over 17,000 participants, the analysis provides high statistical power. The results are stratified by different antidepressants and specific individual symptoms. Two sub-meta-analyses were conducted: one employing the Discontinuation-Emergent Signs and Symptoms (DESS) scale, which is the most established standardized instrument for assessing discontinuation symptoms; the other using various outcome parameters.

“An interesting aspect is the breakdown by individual antidepressants, with angomelatine and vortioxetine—the latter unfortunately no longer reimbursed by health insurance in Germany—showing a particularly favorable profile.

“The present study is very welcome in hopefully correcting worried patients’ impression that antidepressants could cause high rates of withdrawal symptoms as stated by a recent study by Horowitz et al. published in Psychiatry Res. 2025, which, however, is methodologically much weaker than the present one with only 310 patients included in a very specific primary care setting, a very poor response rate of 18% introducing a major bias, and no standardized quantitative outcome measure.

“It is possible that certain subgroups of patients experience more pronounced discontinuation symptoms than others. Future research efforts should focus on identifying the underlying biological and psychological mechanisms—for example, whether these patients metabolize the medications differently, possess a specific genetic background, or whether comorbidities and concomitant medications might account for these reactions.

“This new study is extremely welcome in terms of helping to destigmatize antidepressants. Along these lines, in light of the present results in synopsis with the ones reported by Henssler et al in Lancet Psychiatry in 2024, it is high time to stop referring to ‘withdrawal symptoms’ and instead use the term ‘discontinuation symptoms.’ The term ‘withdrawal’ is traditionally reserved for the context of substance dependence, which, in the case of antidepressants, is simply incorrect.” 

Prof Christiaan Vinkers, Psychiatrist and Professor of Stress and Resilience, Amsterdam UMC, said:

“This is an important and timely study. The topic of antidepressant withdrawal has generated much discussion and concern, although sometimes more heat than light. This new systematic review and meta-analysis in JAMA Psychiatry brings welcome clarity by using rigorous methods and placebo-controlled comparisons. The findings show that, on average, people who stop taking antidepressants experience about one additional discontinuation symptom, most often dizziness, compared to those continuing treatment or stopping placebo. Crucially, the overall symptom burden remained below the threshold for clinically significant withdrawal syndrome. The study also found no increase in depressive symptoms shortly after discontinuation, suggesting that early mood worsening is not a common withdrawal effect but more likely signals relapse.

“Importantly, the authors include unpublished trial data and take into account the nocebo effect, which may inflate perceived symptom rates in open-label studies or uncontrolled settings. This helps temper some of the more alarming claims about universal and severe withdrawal. At the same time, the study acknowledges limitations, including short treatment durations and lack of real-world tapering strategies in most included trials. We still need more data on long-term users, individual vulnerability, and best practices for discontinuation.

“Overall, this is high-quality research that strengthens the evidence base and promotes a more balanced and science-based understanding of antidepressant discontinuation. IIt reminds us that while withdrawal symptoms do occur in a minority of cases, they are on average typically not severe and manageable, especially with proper clinical support.”

‘Incidence and Nature of Antidepressant Discontinuation Symptoms, A Systematic Review and Meta-Analysis’ by Michail Kalfas et al. was published in JAMA Psychiatry at 16:00 UK time on Wednesday 9^th July. 

DOI: 10.1001/jamapsychiatry.2025.1362

Declared interests

Dr Susannah Murphy: SEM has received consultancy fees from Zogenix, Sumitomo Dainippon Pharma, UCB Pharma and Janssen Pharmaceuticals and held grant income from Zogenix, UCB Pharma, Janssen Pharmaceuticals and ADM.

Prof Katharina Domschke: Speaker’s fees by Janssen 

Member of the Neurotorium editorial board, Lundbeck Foundation

Prof Christiaan Vinkers: I am involved in publically ZonMW-funded research on antidepressant discontinuation, including the TEMPO and HARMONIE studies. I am affiliated with the antidepressant discontinuation outpatient clinic in Amsterdam (www.afbouwpoli.nl), and I serve as a member of the Dutch multidisciplinary guideline committee on psychotropic drug discontinuation. I have received a speaker’s fee from Tiofarma, but no financial ties to pharmaceutical companies relevant to this work.

This Roundup was accompanied by an SMC Briefing.