Study finds the rate of withdrawal from quitting antidepressants

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Antidepressants can do wonders for persistent mental health problems. But some people may be reluctant to take the medications, fearing what could happen if they want to stop taking them one day.

That risk has now been quantified, thanks to a new review of 79 studies — known as a meta-analysis — totaling 21,002 adult participants age 45 on average.

Roughly 15% of participants who discontinued antidepressants experienced withdrawal symptoms such as dizziness, headaches, nausea, insomnia and irritability, according to the review published Wednesday in the journal The Lancet Psychiatry.

One in 35 participants experienced severe symptoms once they stopped taking antidepressants. The review is the first publication of a larger project on antidepressant withdrawal symptoms, the authors said.

“There is strong evidence that antidepressants can be effective for many people who are experiencing a depressive disorder, either alone, or alongside other treatments such as psychotherapy,” said Dr. Jonathan Henssler, senior author of the study and senior physician in the department of psychiatry and neurosciences at Charité — University Medicine in Berlin, in a news release.

“However, they do not work for everyone, and some patients may experience unpleasant side effects. In patients who have recovered with the help of antidepressants, the decision from doctors and patients may be to stop taking them in time,” Henssler added. “Therefore, it’s important both doctors and patients have an accurate, evidence-based picture of what might happen.”

The occurrence of withdrawal symptoms was reported or described as early as 1959, but researchers neglected those reports until the late 1990s, according to the review.

Until now, “there has been a lot of ‘debate’ about the important problem of antidepressant withdrawal in the last few years, which has appeared within print and social media, with very high estimates of withdrawal being pronounced at around 50% and half (considered) as severe,” said Dr. Sameer Jauhar, senior clinical lecturer in affective disorders and psychosis at King’s College London, in a news release. Jauhar wasn’t involved in the study.

“This was based on a very unconventional review,” Jauhar added, “which included data from online surveys, which are notoriously difficult to interpret (ask anyone involved in election polling).”

To determine the risk of withdrawal more accurately, the authors reviewed data from 44 randomized controlled trials and 35 observational studies published between 1961 and 2019. These studies investigated abrupt cessation or tapering of an established antidepressant or placebo. More than half of these studies focused on mood disorders such as major depressive disorder or bipolar disorder, and more than a fourth concentrated on anxiety disorders.

The authors also discovered the medications most often linked with withdrawal symptoms were desvenlafaxine, venlafaxine, imipramine and escitalopram. Those with the lowest rate of discontinuation symptoms were fluoxetine and sertraline.

Pharmaceutical companies funded 45 of the studies, but this backing didn’t appear to influence the overall results, according to the review. The rate of withdrawal symptoms in pharma-funded studies was about the same as trials not funded by pharmaceutical companies.

“This work is a salutary lesson, as some people may have been dissuaded from taking a potentially effective treatment, based on poor quality evidence,” Jauhar said. “Science does correct itself, and the authors are to be congratulated on this work.”

The findings are also an important first step to helping patients responsibly discontinue taking antidepressants, said Dr. Christiaan Vinkers, a psychiatrist and full professor in the department of psychiatry at Amsterdam University Medical Center, in a news release.

What these findings mean for patients

Another weakness of the review was that many of the included studies weren’t primarily focused on antidepressant discontinuation, but rather the efficacy of antidepressants versus placebos, Dr. Tony Kendrick, professor of primary care at the University of Southampton in England, said in a news release.

These studies “also happened to observe patients in the wash-out period coming off the drugs at the end of the trials. Consequently, the period of taking the antidepressant was 12 weeks or less in 36 out of the 79 included studies,” Kendrick said. “Severe discontinuation symptoms would not usually be expected to arise after only a few weeks of antidepressant use.”

Some of the other included studies had much longer treatment periods — some up to a year or longer.

Regarding why antidepressant discontinuation sometimes leads to withdrawal symptoms, it’s important to note these medications aren’t addictive, Henssler said. The effects could be due to the suddenly lower amount of neurotransmitters in your brain, according to the Cleveland Clinic.

In the review, there was no difference between studies on tapered or abrupt discontinuation. But the authors cautioned that finding isn’t a firm conclusion due to variation in study designs. And other research still indicates tapering can be helpful for reducing the chances and severity of symptoms, they said.

Though the rates of withdrawal aren’t nearly as high as previously reported, when it comes to patients wanting to quit their antidepressants, doctors should still have conversations about what doing so would mean for the patient and how to do it safely, Jauhar said.

“The doctor should help them to do so slowly and in a controlled manner that limits the impact of any potential withdrawal symptoms … at a pace that suits them and their individual needs,” said Dr. Oliver Howes, chair of the psychopharmacology committee at the Royal College of Psychiatrists in the United Kingdom, said in a news release. Howes wasn’t involved in the study.

Carefully strategizing is important also because of the risk of relapsing into the condition being treated, depending on a person’s mental health history, Dr. Paul Keedwell, a consultant psychiatrist and member of the Royal College of Psychiatrists who wasn’t involved in the study, said in a news release.

The study didn’t provide information on the duration of withdrawal symptoms, but other research suggests they can last for up to two weeks in most cases, Keedwell said. Discontinuation is more difficult for people who have been on their medications for a year or more, he added — in that case withdrawal symptoms can last for months but rarely up to a year.

However, “it is important to say that withdrawal symptoms are not dangerous, and the risk of experiencing them at some future date should not be a reason for refusing antidepressant treatment,” Keedwell said. “The pros and cons of treatment should always be discussed with your doctor.”

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