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Antidepressants: New data on the frequency of discontinuation symptoms

Expectations contribute to symptoms after stopping antidepressants

How difficult is it to stop taking antidepressants? According to numerous internet articles and some scientific studies, discontinuation is very problematic and doctors often underestimate this. However, it was yet to be determined how common the discontinuation symptoms actually are. Researchers from Charité – Universitätsmedizin Berlin and University Hospital Cologne have now comprehensively reanalysed the previous studies. In the paper published in Lancet Psychiatry, they conclude that one in three people report symptoms after discontinuing antidepressant treatment, but half of the symptoms are due to negative expectations.

By formal definition, antidepressants are not addictive. Unlike ‘real’ addictive drugs, for example, taking them does not lead to the body needing an ever-increasing dose for the same effect. Nevertheless, some patients report symptoms such as dizziness, headaches or sleep disorders when they stop taking the mood enhancers. While the phenomenon has been largely neglected in research for many years, there are now a comparatively large number of studies that attempt to quantify the extent of discontinuation symptoms.

“Some of these studies come to very different conclusions,” said Professor Dr Christopher Baethge, scientist at the Scientist at the Department of Psychiatry and Psychotherapy at University Hospital Cologne and the Faculty of Medicine at the University of Cologne. “In recent years, not only the scientific community but also the public has been very actively and sometimes emotionally discussing how frequent and severe the discontinuation symptoms actually are.” A look at the prescription figures shows just how relevant the topic is. According to the latest Drug Prescription Report, almost 1.8 billion daily doses of antidepressants were prescribed in Germany in 2022.

Comprehensive meta-analysis provides clarity

In order to answer this question more reliably than before, a team led by Professor Baethge and Dr Jonathan Henssler, head of the Evidence-Based Mental Health working group at Charité's Department of Psychiatry and Psychotherapy, systematically combed through and re-evaluated the existing studies, i.e. carried out a meta-analysis. It is the first study of its kind to provide the most reliable assessment to date of the consequences of stopping antidepressants. “Our analysis shows that, on average, one in three people experience symptoms after stopping antidepressant treatment,” said Dr Henssler. “However, only half of the symptoms can actually be attributed to the medication.”

For the study, the researchers reviewed more than 6,000 studies, from which they selected 79 studies and statistically re-analysed their results. This resulted in data on around 21,000 people who had received either an antidepressant or a placebo and were subsequently asked about the frequency of discontinuation symptoms. Although around 31 per cent of patients treated with an effective medication reported discontinuation symptoms, 17 per cent of those who had only been given a placebo also complained of this.

Every sixth or seventh person experiences medication-related discontinuation symptoms

“In the placebo group, drug effects can be ruled out, so the symptoms are either due to the fact that they occurred by chance independently of the therapy, or they are a result of the nocebo effect,” explained Dr Henssler. The nocebo effect is often referred to as the ‘brother of the placebo effect’ and describes the observation that sham treatments can be accompanied by ‘side effects’. They are triggered solely by the expectation that the treatment you believe you are receiving will have negative consequences.

“If we take into account non-specific symptoms and the effect of expectations, around one in six or seven people are affected by discontinuation symptoms that occur as an actual consequence of antidepressant medication,” summarized Dr Jonathan Henssler. “These are mostly mild. The vast majority of those affected will be able to discontinue antidepressants without any relevant symptoms. In the vast majority of cases, there is therefore no need for a lengthy or gradual withdrawal of the medication.”

Severe symptoms are rare

According to the study, one in 35 people, i.e. just under three per cent of those affected, developed severe discontinuation symptoms. These occurred more frequently after discontinuation of treatment containing the active substances imipramine, paroxetine, venlafaxine and desvenlafaxine. For some frequently used mood enhancers, not enough information was available to make an assessment.

Professor Dr Christopher Baethge therefore emphasized: “It is important that all people who want to stop treatment with antidepressants receive close medical supervision and individual support in the event of withdrawal symptoms. Joint decision-making between those affected and those treating them, even before starting treatment, is the basis for good treatment. We hope that our data can support this and counteract the current uncertainty.”

About the study

The 79 studies included in the meta-analysis comprised both randomized, placebo-controlled studies and observational studies without a control group. Of the total of 21,002 patients, 16,532 had received an antidepressant and 4,470 a placebo. In addition to the researchers from Charité and University Hospital Cologne, scientists from the University Hospitals of Freiburg and Dresden were also involved in the meta-analysis.

Original publication: Henssler J, Schmidt Y, Schmidt U, Schwarzer G, Bschor T, Baethge C. Incidence of Antidepressant Discontinuation Symptoms - A Systematic Review and Meta-Analysis.Lancet Psychiatry 2024 Jun 05. DOI: 10.1016/S2215-0366(24)00133-0

Source: University Hospital Cologne