About 1 in 6 Who Stop Antidepressants Experience Side Effects, but Rarely Severe
Only about 3% of patients discontinuing their antidepressant had severe withdrawal-like symptoms, although medications including imipramine, paroxetine, and venlafaxine did increase this risk.
Getty Images/iStock/Andrii Yalanskyi
A systematic review and meta-analysis recently published in Lancet Psychiatry provides more confidence to clinicians when they counsel their patients about the risks of discontinuing antidepressant medications.
The study authors found that, after excluding non-specific effects, or effects also observed in people who discontinued a placebo, approximately 15% of patients can be expected to have withdrawal-like symptoms such as headache or irritability that can be directly attributed to discontinuation of an antidepressant. Further, the authors concluded that approximately 3% of patients will experience severe antidepressant-discontinuation symptoms, with an increased risk of severe symptoms in patients prescribed imipramine, paroxetine, and desvenlafaxine or venlafaxine.
“There has been a question of whether antidepressant medications are almost addictive because the withdrawal symptoms are so deep and profound,” said David Gratzer, M.D., attending physician and psychiatrist at the Centre for Addiction and Mental Health in Toronto, Canada, who commended the study authors for a well-executed analysis. “This paper really goes after the question.”
Symptoms of Discontinuation
Jonathan Henssler, M.D., of the University of Cologne, Germany, and colleagues analyzed 79 studies (44 randomized, controlled trials and 35 observational studies) that covered 21,002 patients with mood disorders, anxiety disorders, and other conditions for which antidepressant treatment may be appropriate such as fibromyalgia. A total of 16,532 patients discontinued from an antidepressant, and 4,470 patients discontinued from placebo. The patient population was nearly 72% female, and the mean age was 45. The researchers found the following:
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The incidence rate of at least one discontinuation symptom was 0.31 among patients stopping antidepressants and 0.17 among those stopping placebo.
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The incidence rate of severe discontinuation symptoms was 0.028 among patients stopping antidepressants compared with 0.006 among those stopping placebo.
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Desvenlafaxine, venlafaxine, imipramine, and escitalopram were linked to higher frequencies of discontinuation symptoms.
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Imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms.
“What they were able to show is some element of discontinuation occurs in many patients, but actually severe symptoms are pretty rare,” Gratzer said. “I don’t think psychiatrists in practice are going to be exactly stunned by the results.”
Looking at discontinuation symptoms in patients who had been on a placebo was “a nice touch,” Gratzer added. He said this consideration factors in the “nocebo” effect, in which patients experience symptoms due to negative expectations that stopping a medication will cause side effects.
Information and Misinformation
In an age where patients can research their conditions and medications online and on social media and can be exposed to inaccurate information or misinformation around the use of antidepressants, such a study will better equip psychiatrists to discuss the subject of discontinuation symptoms with their patients, according to Gratzer.
“Our patients read more than they have ever read before,” Gratzer said. “They have access to things that historically they did not have access to. They can read [peer-reviewed] journals like I do. The flipside is that the ability to find misinformation is greater than ever.
“If we can help our patients understand things better, that is important,” Gratzer said. “When the patient in front of you thinks about starting an antidepressant, he should weigh the risks and benefits, of course. Some misinformation has suggested that he is stuck [taking the antidepressant indefinitely], and thus if he starts the pill at age 21, that he will be still taking it at age 81.”
The authors did not uncover a difference in the incidence of discontinuation symptoms between studies that tapered the drug dose and studies that discontinued immediately, but noted that there was much heterogeneity in study designs. Despite not seeing a difference, the authors pointed to clinical guidelines that recommend tapering antidepressants when they are being discontinued to help prevent adverse symptoms in patients.
“Most of the evidence favors tapering,” Gratzer said. “A focused, thoughtful titration might be one approach.”
What to Tell Patients
Jonathan E. Alpert M.D., Ph.D., chair of psychiatry and behavioral sciences at Montefiore Medical Center and professor of psychiatry, neuroscience, and pediatrics at Albert Einstein College of Medicine in the Bronx, agreed that while some people require long-term treatment with antidepressants for clinical reasons, the idea that people need to stay on antidepressants indefinitely in order to stave off discontinuation-related side effects is not supported by the literature.
“The Lancet paper has helped put some brackets on that [notion], as it showed that having anything more than mild or moderate side effects upon discontinuation of antidepressants is unlikely, and that only about one in six people have side effects that are directly attributable to stopping the antidepressant,” said Alpert, who is also chair of APA’s Council on Research.
A limitation that Alpert pointed out is that some common antidepressants, such as bupropion or mirtazapine, were not included. “They didn’t happen to find studies on these, but neither of those stand out as being particular offenders when it comes to withdrawal effects,” he said.
Based on the conclusion of this systematic review and meta-analysis, psychiatrists can call attention to the enhanced risk of discontinuation symptoms when they are on specific antidepressants, according to Alpert, who said: “We should specifically underscore [this risk] for the medications that are more likely to cause side effects.”
There was no funding source reported for this study. ■
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Published online: 28 August 2024
Published in print: September 1, 2024 – September 30, 2024
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