Summary: The largest review of antidepressant withdrawal studies to date finds that most people stopping these medications do not experience severe discontinuation symptoms. After analysing data from nearly 18,000 participants, researchers report that the most frequent reactions were generally mild—dizziness, nausea, vertigo and nervousness—rather than serious or long-lasting effects.
Importantly, stopping antidepressants in these trials was not associated with relapse into depression, suggesting that ongoing or worsening mood symptoms after discontinuation are more likely to represent a recurrence of the underlying illness rather than a withdrawal syndrome. These results offer reassurance for patients and practical guidance for clinicians managing antidepressant discontinuation.
Key facts:
- Mild symptoms: Most people experienced only one mild symptom when stopping antidepressants, below thresholds used to define clinically important discontinuation syndrome.
- No relapse link: Data did not show an association between withdrawal and relapse of depression in the included randomised trials.
- Drug-specific effects: Discontinuation profiles varied by medication; venlafaxine showed higher rates of symptoms than several other drugs in the analysis.
Source: Imperial College London
The largest systematic review and meta-analysis of randomised controlled trials evaluating antidepressant discontinuation has clarified which symptoms commonly occur and how frequent they are, concluding that most people do not experience severe withdrawal.
Researchers from Imperial College London, King’s College London, UCL and other UK institutions pooled and analysed results from 50 trials, comprising 17,828 participants with an average age of 44 years; about 70% of participants were female. The review examined trials that measured discontinuation symptoms both with a standardised instrument—the Discontinuation Emergent Signs and Symptoms scale (DESS)—and with a range of other symptom or adverse event measures.
Overall, discontinuing antidepressants was associated with an increase equivalent to roughly one extra symptom on the 43-item DESS at one week after stopping—below the commonly used cut-off of four or more symptoms for a clinically significant discontinuation syndrome. In placebo-controlled randomised trials the most common symptoms and their approximate frequencies in those who stopped medication versus placebo were: dizziness (7.5% vs 1.8%), nausea (4.1% vs 1.5%), vertigo (2.7% vs 0.4%) and nervousness (3% vs 0.8%).
Some symptoms were more likely to be drug-specific. For example, discontinuation of venlafaxine showed higher rates of dizziness—around 20%—compared with 1.8% in placebo groups. Vortioxetine produced fewer than one additional symptom on the DESS on average, and no additional symptoms were detected with agomelatine in the analysed trials. Including non-placebo-controlled studies modestly increased estimated rates for some symptoms (dizziness 11.8%, nightmares 8.1%, nervousness 7.6%, nausea 5.8%).
Crucially, across the trials included in this review, stopping antidepressants was not associated with the emergence of depressive symptoms signalling relapse, even among participants who had an existing diagnosis of major depressive disorder. That distinction helps clinicians identify when new symptoms represent a true recurrence of illness rather than a transient discontinuation reaction that will resolve.
Most trials in the review (44 of 50) used abrupt discontinuation or a short one-week taper, so the findings are strongest for the early period after stopping treatment. The authors note a limitation: the majority of included studies followed participants for up to two weeks post-discontinuation, which constrains conclusions about longer-term withdrawal or protracted symptoms. Nevertheless, longer-term data from the ANTLER trial, which was included in this review, also indicated that severe, persistent withdrawal after prolonged use is infrequent.
Lead author Dr Sameer Jauhar (Imperial College London) said the findings should reassure the public and clinicians by identifying the most likely symptoms to monitor and by showing that most people do not experience severe withdrawal. Co-author Michail Kalfas (King’s College London) highlighted that a sub-group may still develop more pronounced discontinuation reactions and emphasised the need for further research into biological and metabolic factors that could explain individual vulnerability.
Professor Allan Young (Imperial College London) commented that this robust meta-analysis clarifies scientific evidence on discontinuation and supports updating clinical guidance to reflect that antidepressant stopping effects are real, vary between drugs, but are not inevitable for most patients.
About this mental health and psychopharmacology research news
Author: Samantha Rey
Source: Imperial College London
Contact: Samantha Rey – Imperial College London
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Incidence and Nature of Antidepressant Discontinuation Symptoms, A Systematic Review and Meta-analysis” by Sameer Jauhar et al. JAMA Psychiatry
Abstract
Incidence and Nature of Antidepressant Discontinuation Symptoms, A Systematic Review and Meta-analysis
Importance
The incidence and nature of discontinuation symptoms following antidepressant cessation remain uncertain and clinically important to clarify for patients and prescribers.
Objective
To assess discontinuation symptoms using standardised scales such as the DESS and to quantify the incidence of individual symptoms after stopping antidepressant medications.
Data Sources
Systematic searches were run across Embase, PsycINFO, Ovid MEDLINE and the Cochrane Library up to November 7, 2023.
Study Selection
Randomised clinical trials reporting discontinuation symptoms using standardised instruments or individual symptom reporting were included.
Data Extraction and Synthesis
Two reviewers cross-checked extracted data; unpublished data from 11 trials were incorporated. Random-effects meta-analyses estimated standardised mean differences for DESS scores and odds ratios for individual symptoms compared with placebo discontinuation. Subgroup comparisons examined different antidepressant agents. Analyses were conducted between September and December 2024.
Main Outcomes and Measures
Primary outcomes were the incidence and character of antidepressant discontinuation symptoms measured by standardised or other scales.
Results
Fifty studies were included (49 in meta-analyses) with 17,828 participants (66.9% female; mean age 44). Follow-up ranged from 1 day to 52 weeks. The DESS meta-analysis found a small increase in discontinuation symptoms at one week after stopping antidepressants (standardised mean difference, 0.31), equivalent to about one extra symptom on the DESS. Discontinuation increased odds of dizziness, nausea, vertigo and nervousness vs placebo, with dizziness the most common symptom (risk difference 6.24%). Discontinuation was not associated with depressive symptoms in trials including people with major depressive disorder.
Conclusions and Relevance
This systematic review and meta-analysis indicates that, at one week after stopping antidepressants, the average number of discontinuation symptoms is below thresholds for clinically significant syndrome. Worsening mood was not linked to discontinuation in these trials, so later presentation of depressive symptoms after stopping treatment is more likely to signify relapse of the underlying disorder.