Stopping antidepressants causes withdrawal symptoms in 15% of patients, meta-analysis finds

More than one in six patients who stop taking antidepressants will experience withdrawal symptoms as a direct result, a systematic review and meta-analysis published in The Lancet Psychiatry has found.

The study, published on 5 June 2024, aimed to review all available evidence to establish the incidence of discontinuation symptoms, including severe symptoms, and the differences in withdrawal symptoms between antidepressants. The authors described it as the first meta-analysis on antidepressant withdrawal symptom incidence.

It also looked to identify the difference between symptoms directly caused by stopping medication and ‘non-specific’ symptoms that may be associated with patients’ or practitioners’ expectations, known as the ‘nocebo effect’.

Researchers conducted a review and meta-analysis of 79 studies (44 randomised control trials and 35 observational studies), which included data from 21,002 patients, of which 16,532 patients discontinued from antidepressants and 4,470 patients discontinued from placebo. 

Overall, the analysis found that a third (31%) of patients who stopped taking an antidepressant experienced at least one symptom, such as dizziness, headache, nausea, insomnia and irritability, after discontinuation. Severe symptoms occurred in about 3% of patients (1 in 35). Some antidepressants were also associated with a higher risk of severe symptoms compared with others.

When looking at the results from randomised controlled trials, the researchers found that one in six patients (17%) experienced discontinuation-like symptoms when stopping taking a placebo drug. The authors said that this suggests approximately half of all symptoms experienced in those stopping antidepressants might be non-specific or owing to the nocebo effect.

In conclusion, the authors estimated that one in six to seven (15%) patients will experience one or more discontinuation symptoms that are directly caused by stopping antidepressants.  

Study co-author Christopher Baethge from the University of Cologne said: “Our findings do not imply that some symptoms experienced by people during antidepressant discontinuation are not ‘real’ or that all discontinuation symptoms are due to expectations on the part of patients.

“Any symptoms that cause patients discomfort or distress should be taken seriously, and the patient should be supported. The patient and clinician should discuss which of the symptoms might be directly caused by stopping antidepressants and how best to manage all symptoms.”

While the analysis did not find a difference in withdrawal symptoms between studies that applied tapering and those where medication was stopped suddenly, the authors said these were not firm conclusions, and further research was needed. They also highlighted how previous single study results indicated that tapering may be helpful in decreasing severity and incidence of discontinuation symptoms.

Commenting on the study, Nicola Greenhalgh, deputy chief pharmacist, inpatient, specialist and secure services at Essex Partnership University NHS Foundation Trust, and vice president of the College of Mental Health Pharmacy, said: “As a large meta-analysis it helps to provide some update and context to the concerns around antidepressant discontinuation, particularly as it is able to differentiate between true antidepressant discontinuation reactions compared to that that is also seen when discontinuing a placebo.

“There has been a lot of focus more recently on how we stop antidepressants; some of the guidance that has been produced is complicated for patients and may risk errors or further problems. The study also supports information we have on those medications not only more likely to cause discontinuation symptoms but also those which are more likely to cause severe effects.

“Whilst extended tapering regimes may be required for some patients, this study will hopefully give some reassurance that such regimes aren’t needed routinely and help identify those patients more likely to experience problems.”

David Taylor, director of pharmacy and pathology at South London and Maudsley NHS Foundation Trust, said: “My observations over more than 30 years of speaking to people stopping antidepressants is that the large majority of them experience discontinuation effects. Nocebo effects seem unlikely because few people are aware of the nature of withdrawal effects before stopping antidepressants.

“The paper suggests that 3% of people have serious withdrawal reactions. If this is correct, it represents millions of people around the world. Around 1% of people (80 million) take antidepressants. This would mean 2.4 million [people] experiencing a severe reaction on stopping.”

Stephen Bazire, honorary professor at the University of East Anglia School of Pharmacy, welcomed the paper’s findings, citing further examples of antidepressant withdrawal studies.

“Two more recent and large naturalistic studies, carried out by pharmacists in Rotherham and Sunderland… have shown that planned and steady withdrawal of antidepressants produced discontinuation symptoms in fewer than 5% of people,” he said.

“Let’s hope this comprehensive review reassures people who take antidepressants that they are not addicted and, if stopped in a planned and structured way, will have few if any serious problems,” he added. 

Adults with depression who are stopping their antidepressants should have the dose reduced in stages, according to one of several new measures included in a quality standard published by the National Institute for Health and Care Excellence in 2023.