A systematic review and meta-analysis of stopping antidepressants found that while one in three people report symptoms upon stopping, half are likely due to the nocebo effect. Serious symptoms are rare and affect only about 3% of people who stop treatment. Credit: Issues.fr.com
Expectations contribute to symptoms after stopping antidepressants.
Is it difficult to stop taking antidepressants? If countless Internet publications and multiple scientific studies are to be believed, stopping these medications is very problematic and doctors often underestimate the difficulties involved. However, it is unclear how common treatment discontinuation symptoms actually are. Researchers from Charité – Universitätsmedizin Berlin and University Hospital Cologne conducted a systematic review and meta-analysis. In their article in The Lancet In psychiatry, they conclude that one in three people report symptoms after stopping antidepressant treatment, but that half of these symptoms are attributable to negative expectations (nocebo effect).
Exploring the Nocebo effect in antidepressant withdrawal
According to the formal definition, antidepressants are not addictive. Unlike “real” addictive substances, for example, taking them does not force the body to require increasingly higher doses to achieve the same effect. Despite this, many patients report symptoms such as dizziness, headaches, or insomnia when they stop taking these mood medications. The phenomenon remained largely ignored by researchers for years, but there are now a relatively large number of studies seeking to quantify the extent of treatment discontinuation symptoms.
Varied Findings in Dropout Studies
“The results of these studies vary, in some cases considerably,” explains Professor Christopher Baethge, researcher at the Department of Psychiatry and Psychotherapy at the University Hospital Cologne and at the Medical Faculty of the University of Cologne. “There have been many discussions, sometimes very emotional, within the research community and the general public in recent years about the true prevalence and severity of withdrawal symptoms. » A look at the prescription figures shows how relevant this topic is. According to the latest Arzneiverordnungs report, which summarizes data on drug prescriptions, almost 1.8 billion daily doses of antidepressants were prescribed in Germany in 2022.
The difficulty of stopping antidepressants is often discussed with emotion. A meta-analysis now sheds light on the true frequency of treatment discontinuation symptoms. Credit: © Charité | Romy Greiner
Comprehensive meta-analysis provides clarity
To answer this question more reliably than before, a team led by Christopher Baethge and Dr. Jonathan Henssler, head of the Evidence-Based Mental Health Research Group at Charité’s Department of Psychiatry and Neuroscience, conducted a systematic review of existing studies and re-analyzed them in what is called a meta-analysis. As the first study of its kind, it provides the most robust assessment to date of the consequences of stopping antidepressant treatment. “Our analysis shows that on average, one in three people will experience symptoms after stopping antidepressant treatment,” says Henssler. “However, only half of these symptoms are actually attributable to the drug itself. »
Placebo influence and actual withdrawal symptoms
For their article, the researchers examined more than 6,000 studies. They then selected 79 of them and re-analyzed the results of these trials using statistical methods. Ultimately, they analyzed data from about 21,000 people who received either an antidepressant or a placebo and then asked about the prevalence of discontinuation symptoms. Some 31 percent of patients treated with an active drug reported discontinuation symptoms, as did 17 percent of those who received a placebo alone.
“Drug effects can be excluded in the placebo group, meaning that the symptoms either appeared by chance, independent of the treatment, or were the product of the nocebo effect,” explains Henssler. The nocebo effect is often considered a reflection of the placebo effect. This explains the observation that inactive treatments may be associated with “side effects.” These effects are triggered solely by the expectation that the treatment people think they are receiving will have negative effects.
Incidence and severity of withdrawal symptoms
“When we take into account nonspecific symptoms and the effect of expectancies, about one in six or seven people are affected by discontinuation symptoms that occur as a real consequence of antidepressant treatment,” says Henssler, summarizing the results of the study. “In most cases, the symptoms are mild. The vast majority of affected people will be able to stop antidepressants without experiencing relevant symptoms. This means that in most cases there is no need for a lengthy or gradual reduction process.
Managing and Alleviating Severe Withdrawal Symptoms
The study found that serious symptoms of stopping treatment are experienced by one in 35 people, or almost three percent of those affected. These types of symptoms were more common after stopping treatment with imipramine, paroxetine, venlafaxine, and desvenlafaxine. Researchers did not yet have enough information to assess the status of a number of widely used antidepressants.
As Baethge emphasizes: “It is important that all people wishing to discontinue treatment with antidepressants are monitored and advised by healthcare professionals and receive individual support in the event of withdrawal symptoms. Joint decision-making between the patient and the prescriber even before treatment begins is the basis of good treatment. We hope our data will help patients and healthcare professionals and help alleviate some of the uncertainty surrounding these issues today.
To learn more about this study, see Getting Off Antidepressants: Study Reveals Risk of Discontinuation Symptoms.
The 79 studies included in the meta-analysis included both randomized placebo-controlled trials and observational studies conducted without a control group. Of the 21,002 patients involved in the studies, 16,532 had received an antidepressant and 4,470 a placebo. In addition to researchers from Charité and the University Hospital Cologne, researchers from the University Medical Center Freiburg and the Carl Gustav Carus University Hospital Dresden participated in the meta-analysis.
