For adults who have recovered from depression with the help of antidepressants, gradually reducing medication together with psychological support appears to be as effective as remaining on antidepressants for preventing relapse, according to a systematic review and network meta-analysis of 76 randomised controlled trials, published in The Lancet Psychiatry journal.
The authors emphasise that these findings do not suggest that antidepressants are unnecessary or that psychotherapy alone is adequate. Instead, they say the results underscore the importance of tailoring deprescribing to each individual, with a gradual individualised tapering of antidepressants alongside structured psychological support.
"Depression is often a recurring condition and without ongoing treatment as many as three out of four people with recurrent depression relapse at some point," said lead author Professor Giovanni Ostuzzi from the University of Verona in Italy. "Clinical guidelines recommend continuing antidepressants for a certain period after remission, then considering discontinuation once the person has remained well. Yet in everyday practice, treatment is often prolonged far beyond what guidelines suggest. Many people do not wish to stay on medication indefinitely, and some experience troublesome side-effects. Still, there has been little rigorous research into the safest and most effective approaches to discontinue treatments."
He continued, "By incorporating a substantially larger evidence base, a broader range of deprescribing strategies, and direct head-to-head comparisons, our new review clarifies the scientific evidence about the most effective way to come off antidepressants for individuals successfully treated for depression and could change how coming off antidepressants is managed globally."
He added, "We encourage anyone considering coming off antidepressants to discuss the process with their doctor first to jointly find the best strategy for them."
Evidence-based guidelines for moderate-to-severe depression and anxiety disorders typically recommend that antidepressants be taken for six to nine months after a first episode, or for up to two years in people who have experienced multiple recurring episodes or have specific risk factors for relapse. But there are concerns about overprescribing, long-term use, and withdrawal symptoms after discontinuation which underscore the need for evidence-based deprescribing strategies.
To address this evidence gap, researchers conducted the largest and most rigorous analysis of randomised controlled trials to date, examining antidepressant deprescribing strategies up to April 2025.
They analysed data from 76 randomised controlled trials involving 17,379 adults (average age of 45 years, 68% female, 88% White) with fully or partially remitted depression (defined as mild-to-negligible symptoms but diagnostic criteria not fulfilled; 60 studies) or anxiety disorders (16 studies) receiving antidepressant treatment (mostly selective serotonin-reuptake inhibitors [SSRIs] or serotonin norepinephrine reuptake inhibitors [SNRIs]) who were followed for an average of 10 to 11 months.
The network meta-analysis directly compared the effectiveness of all major strategies for deprescribing on the rate of relapse (a new episode of depression or anxiety) each with or without psychological support:
- sudden stopping of an antidepressant (replaced by a placebo pill)
- fast tapering (reducing the medication dose over four weeks or less)
- slow tapering (reducing the medication dose over more than four weeks)
- dose reduction (50% or less of the minimal effective dose)
- or continuing antidepressant treatment
Overall, the analysis found moderate-quality evidence that after successful treatment of depression, slow tapering of antidepressants combined with psychological support prevented relapse over the following year to a similar extent as remaining on an antidepressant at standard doses (either with or without psychological support). These were the most effective strategies for reducing the rate of depression relapse. (See figure 3 in the paper for the full comparison of strategies).
The researchers estimated that slow tapering of antidepressants plus psychological support could prevent one relapse in every five individuals compared with abrupt stopping or fast tapering (the two least effective strategies) - offering a clinically meaningful benefit.
The analysis also found that continuing with reduced antidepressant doses was better than abruptly stopping and fast tapering for reducing relapse, but the evidence for this was less strong.
Additionally, combining psychological support with either slow or fast tapering was significantly more effective at reducing relapse than fast or slow tapering alone, however the quality of evidence for this was low.
No significant differences in reported side effects or number of dropouts were seen between the deprescribing strategies. However, information on withdrawal symptoms and other clinically relevant factors was scarce or missing, limiting insights into the potential influence of withdrawal symptoms, as well as quality of life and social functioning.
For anxiety, the authors note that the evidence was less robust and requires confirmation in dedicated trials to provide doctors and patients with accurate evidence-based information on which to base their decisions.
"Our findings suggest that while antidepressants are effective in preventing depressive relapses, they do not need to be a long-term treatment for everyone," said co-author Dr Debora Zaccoletti from the University of Verona. "Safe alternative treatments like psychological support, including cognitive behavioural and mindfulness-based therapies, can be a promising tool—even in the short-term. However, considerable healthcare resources are needed to develop and implement dedicated psychotherapy approaches in clinical practice so more cost-effective, short-term, scalable and remotely delivered interventions should be tested and prioritised."
She added, "These findings highlight the need for clinical guidelines to be updated to promote regular treatment reviews and individualised deprescribing with gradual tapering and structured psychological support for patients with depression who are feeling better and wish to come off their medication."
Writing in a linked Comment, Dr Jonathan Henssler, Charité–Universitätsmedizin Berlin (Germany), who was not involved in the study, said: "One of the most consistent findings of the analysis is that adjunctive psychological support or psychotherapy resulted in improved outcomes for all the different pharmacological strategies. Although this might seem a trivial finding, it is of substantial clinical importance.
He continues, "Another crucial finding from Zaccoletti and colleagues' analysis […] warrants emphasis: the best patient outcomes were achieved with strategies that maintained antidepressant therapy. This finding serves as a reminder of the severity and chronicity of depression in many cases and, notwithstanding the preference for minimising pharmacotherapy duration, highlights the limitations of the current curative capacity of antidepressant therapies. Importantly, this limited capacity applies equally to psychotherapy, whose effect sizes are no better than those of pharmacotherapy."
