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A systematic review and network meta-analysis published in Lancet Psychiatry looks at antidepressant deprescribing strategies.
Prof Christiaan Vinkers, psychiatrist and Professor in stress and resilience, Amsterdam UMC, Amsterdam, the Netherlands, said:
“This is the most comprehensive review to date of different antidepressant discontinuation strategies. Slower discontinuation over one or more months combined with psychological support emerges as a safe and effective approach. Abrupt stopping or very rapid tapering shows a clearly higher risk of relapse. At the same time, the certainty of evidence is mixed and often low, and key questions about optimal tapering steps and withdrawal symptoms remain unanswered. This highlights the need for individualised planning and clinical support.”
Dr Prasad Nishtala, Reader in Pharmacy and Epidemiology, University of Bath, said:
“Evidence from this network meta-analysis shows that gradual antidepressant dose reduction over more than four weeks, alongside psychological support, prevents relapse as effectively as continuing antidepressants at full therapeutic doses. This approach significantly outperforms abrupt discontinuation and rapid tapering, both of which carry substantially higher relapse risks. The number needed to treat is approximately five compared with stopping abruptly, indicating a clinically meaningful benefit.
“What was previously known was that antidepressant discontinuation in individuals with remitted symptoms increases the risk of relapse compared with antidepressant continuation. Hence, this network analysis sheds evidence that antidepressant deprescribing alongside psychological support is as effective in preventing relapse as continuing antidepressants at full therapeutic doses. Clinically, this may be important if patients experience side effects from antidepressants or are unable to tolerate high antidepressant doses or are on a cocktail of drugs.
“Importantly, continuation strategies whether at full dose or at a reduced dose provide strong protection against relapse, with standard-dose continuation remaining one of the most reliable options. Reduced dose continuation shows benefit over abrupt stopping, though with lower certainty, and may be suitable for individuals who prefer some decrease in medication exposure but are at higher risk of relapse. Psychological support meaningfully enhances the success of tapering but does not show clear benefit when provided alongside abrupt discontinuation or unchanged medication regimens, emphasising its value specifically during a structured withdrawal process.
“Across all deprescribing strategies, tolerability and adverse events were broadly comparable, with no major safety concerns identified. Withdrawal symptoms were difficult to assess due to inconsistent reporting but appeared more common in those continuing antidepressants, suggesting misclassified side effects rather than true withdrawal phenomena. The evidence is strongest for major depression, with fewer data for anxiety disorders, although results were broadly consistent. Overall, clinicians should avoid abrupt or rapid tapering (which is already known) and instead employ personalised, gradual tapering supported by psychological interventions, alongside careful monitoring in the first year after medication discontinuation.
“The authors have highlighted several limitations, but one important caveat is that most trials included in this study followed patients for less than a year. Therefore, the results apply mainly to short-term relapse risk, with limited insights into long-term relapse risk beyond the first year after discontinuation.”
Dr Sameer Jauhar, Clinical Associate Professor in Affective Disorders and Psychosis, Imperial College London, said:
“This is an interesting analysis of whether continuing antidepressants prevents relapse of depression. We know from long-term cohort data that roughly 60–70% of people who have a first episode of depression will have a further episode over time, and good continuation trials suggest that maintenance antidepressants roughly halve that risk. The headline claim here, that slow tapering plus psychological therapy is as effective as staying on antidepressants, needs to be tempered down, and interpreted with caution.
“It rests on a small group of relapse-prevention trials (less than 5% of the total sample) in which, on closer inspection, somewhere between about a quarter and over half of participants in the ‘slow taper + therapy’ arms were still taking or had restarted antidepressants during follow-up.
“Those data therefore do not show that psychological support can replace maintenance medication; they show that carefully supported tapering works for some, while many still need ongoing pharmacological treatment. The question of what happens when people stop is better addressed by randomised discontinuation trials such as ANTLER, which has already shown that risk of relapse over a year is substantially higher after stopping long-term antidepressants (around 60%) than continuation (around 40%). That underlines both the protective effect of maintenance treatment and the sobering fact that neither medication nor psychotherapy alone is sufficient for many people. We still need better, more integrated and personalised medical, psychological and social interventions.”
Prof Hamish McAllister-Williams, Professor of Affective Disorders, Newcastle University and Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust, said:
“Zaccoletti and colleagues report an analysis of a large number of studies investigating the likelihood that a person with depression or anxiety will relapse if they stop taking antidepressants. The clearest finding is that stopping antidepressants – through any discontinuation method and in the absence of psychotherapy – at least doubles the chances of becoming ill again over the next 6-12 months. The study also provides some support suggesting that if a person is going to stop an antidepressant that it is better to do this over at least 4 weeks, and that having psychotherapy at the time may also help. This is useful information for patients and clinicians.
“However, more contentiously, the authors suggest that slowly stopping an antidepressant and having psychotherapy is as likely to keep you as well as continuing on an antidepressant. The largest study this conclusion is based on actually showed that psychotherapy alongside slow tapering is only better than continuation of an antidepressant which is not working very well.
“It is vitally important that patients do not think this study says there is no risk involved in stopping an antidepressant as long as they do it slowly. There still remains a risk they could still relapse.”
Prof Ian Maidment, Professor in Clinical Pharmacy, Aston University, said:
“The study reviewed the clinical trials that involved stopping or reducing the dose (also called de-prescribing) of anti-depressants. The people involved had suffered from depression or anxiety, which had been successfully treated with anti-depressants. It is one of the largest studies so far conducted involving over 17,000 adults.
“The study showed that the safest way to stop anti-depressants, and avoid the symptoms of depression or anxiety returning, is to gradually reduce the dose, over at least one month, with psychological support. There a number of limitations with the study. First, the classification of slow versus fast stopping was arbitrary and in practice many people stop anti-depressants over very long periods. Second, withdrawal symptoms were poorly recorded. Third, the people in the study mainly suffered from depression rather than anxiety.
“Overall, this study confirms what is already known. Once depression or anxiety has been successfully treated the best way to stop the anti-depressant is very gradually over long periods of time – in some cases many months, or more. Patients should be supported during the process.”
‘Comparison of antidepressant deprescribing strategies in individuals with clinically remitted depression: a systematic review and network meta-analysis’ by Debora Zaccoletti et al. was published in Lancet Psychiatry at 23:30 UK time on Wednesday 10th December.
Declared interests
Prof Christiaan Vinkers: Founder Antidepressant Discontinuation Clinic Amsterdam, co-PI TEMPO trial (RCT on antidepressant discontinuation), member of coming Dutch guideline psychotropic drug discontinuation.
Dr Prasad Nishtala: No COI
Dr Sameer Jauhar: Dr Jauhar reported personal fees from Recordati, LB Pharmaceuticals, Boehringer Ingelheim, Wellcome Trust, Lundbeck, Janssen, and Sunovion, and non-financial support from the National Institute for Health and Care Excellence, British Association for Psychopharmacology, and Royal College of Psychiatrists.
Prof Hamish McAllister-Williams: Prof McAllister-Williams is Director of Education for the British Association for Psychopharmacology
Prof Ian Maidment: No conflicts of interest
This Roundup was accompanied by an SMC Briefing.