The largest study to date on antidepressants is conclusive: They must be discontinued slowly and with therapy

The largest study published to date is clear: the only way to stop taking antidepressants is slowly and with psychological support. Doing so prevents relapse into depression to a similar extent as remaining on antidepressants. This study, published in the journal The Lancet Psychiatry, is relevant for several reasons: 30% of people who are prescribed antidepressants do not actually have depression; 40% take them for five years or more; and 22% take them indefinitely. However, this treatment has adverse side effects if taken for a long time, particularly sexual dysfunction and a reduced ability to express feelings. The study, which reviews 76 controlled trials involving 17,000 people, underscores the importance of tailoring the prescription to each individual, with a gradual and individualized withdrawal of treatment, along with psychological support.

“Depression is often a recurring condition and without continuous treatment; up to three out of four people with depression relapse at some point,” explains Giovanni Ostuzzi, a researcher at the University of Verona and lead author of the study. “Clinical guidelines recommend continuing antidepressants for a certain period after remission and then considering discontinuing them once the person is well. However, in daily practice, treatment often lasts much longer than the guidelines suggest,” Ostuzzi added at a press conference organized this week by the SMC website.

The meta-analysis compared different antidepressant withdrawal strategies in people with depression or anxiety who were already in remission. The conclusion was that slow withdrawal (more than four weeks), combined with psychological support, prevented relapse in the following year to a similar extent as continuing the antidepressant. The researchers estimated that slow withdrawal plus psychological support could prevent one relapse in every five individuals compared to abrupt discontinuation or rapid withdrawal (four weeks or less), which were the two least effective strategies.

“One of the most consistent findings of the analysis is that psychological support or complementary psychotherapy proved more effective for all the different pharmacological strategies,” notes Jonathan Henssler of Charité Hospital in Berlin, in a commentary accompanying the article. “Although this may seem like a trivial finding, it is of substantial importance,” adds the expert, who was not involved in the study.

Henssler warns that psychological treatment “is often the hardest thing for patients to obtain in the real world [...] Internet forums illustrate the extent to which patients rely on self-help and how professional psychiatric and psychological support remains inadequate,” Henssler adds. And the data indicates that more and more people are turning to artificial intelligence to resolve their psychological problems, although chatbots carry many risks: they reinforce self-centered thoughts and paranoid ideas.

The 76 trials under analysis primarily included individuals with major depressive disorder and various anxiety disorders. The mean age of participants was 45 years, 67.5% were women, and 88% were white. The mean follow-up period was 46 weeks.

A major limitation of the study is the scarcity of data on withdrawal symptoms, despite the fact that these are clearly one of the main barriers to discontinuing treatment. “Due to the lack of data in most studies, we sought to identify adverse events plausibly related to withdrawal,” the authors explain. However, they also note that these problems were more frequent in individuals who continued taking antidepressants than in those who discontinued them quickly, suggesting that they are likely side effects of the antidepressant rather than withdrawal symptoms.

The authors believe their findings have significant implications for clinical practice and health policy. Guidelines, they insist, should promote regular treatment reviews. Abrupt or rapid discontinuation of antidepressants (within a month or less) should be strongly discouraged, they emphasize, and a more gradual and individualized withdrawal plan should be implemented. They also believe that providing psychological support is essential. The authors themselves acknowledge, however, the difficulty of implementing this recommendation within the public healthcare system.

Gerard Anmella, a psychiatrist and researcher at the Depressive and Bipolar Disorders Unit of the Hospital Clínic of Barcelona, who was not involved in the study, agrees: “Is it feasible to implement this strategy in healthcare systems? In the public system, offering brief psychological support systematically during discontinuation is challenging due to financial and staffing limitations. Even so, the results point to the need to integrate brief, protocol-based psychological interventions, given their potential impact on reducing relapses,” he explained to the SMC Spain website.

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