15% of patients experience antidepressant discontinuation symptoms, which are mostly mild

Key takeaways:

• Incidence rates of antidepressant discontinuation symptoms included 0.31 for antidepressants and 0.17 for placebo.
• Imipramine, paroxetine and desvenlafaxine or venlafaxine had the most severe symptoms.

Discontinuation symptoms occurred in one in three people who stopped taking antidepressants, and in one in six people who discontinued placebo, according to research published in The Lancet Psychiatry.

When considering nonspecific effects, researchers thus estimated that 15% of patients, or one in six to seven, stopping antidepressant medication will experience discontinuation symptoms, and one in 35 patients will experience severe symptoms.

“Our analysis shows that, on average, one in three people experience symptoms after stopping antidepressant treatment,” Jonathan Henssler, MD, head of the Evidence-Based Mental Health working group in the department of psychiatry and psychotherapy at Charité – Universittsmedizin Berlin, said in a related press release. “However, only half of the symptoms can actually be attributed to the medication.”

Henssler and colleagues conducted a systematic review and meta-analysis of 79 studies that evaluated discontinuation of antidepressants or placebo. These studies included 21,002 patients (72% women; mean age, 45 years; range, 19.6-64.5), of whom 16,532 discontinued antidepressants and 4,470 discontinued placebo.

The incidence rate (IR) of any antidepressant discontinuation symptom was 0.31 (95% CI, 0.27-0.35) after discontinuation of antidepressants, compared with 0.17 (95% CI, 0.14-0.21) after discontinuation of placebo.

Some medications were associated with higher rates of symptoms, including imipramine (IR = 0.44; 95% CI, 0.25-0.66) and desvenlafaxine or venlafaxine (IR = 0.4; 95% CI, 0.35-0.45), whereas fluoxetine (IR = 0.15; 95% CI, 0.01-0.8) and sertraline (IR = 0.18; 95% CI, 0.08-0.35) had the lowest rates of discontinuation symptoms.

The incidence of severe antidepressant discontinuation symptoms was 0.028 (95% CI, 0.014-0.057) for antidepressants and 0.006 (95% CI, 0.002-0.013) for placebo. Medications associated with the highest rates of severe antidepressant discontinuation symptoms included imipramine (IR = 0.123; 95% CI, 0.015-0.577), paroxetine (IR = 0.053; 0.025-0.107) and desvenlafaxine or venlafaxine (IR = 0.056; 95% CI, 0.002-0.678).

“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,” Henssler said in the release. “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.”

References:

• Antidepressants: New data on the frequency of discontinuation symptoms. https://portal.uni-koeln.de/en/universitaet/aktuell/press-releases/single-news/antidepressants-new-data-on-the-frequency-of-discontinuation-symptoms. Published June 6, 2024. Accessed June 11, 2024.
• Henssler J, et al. Lancet Psychiatry. 2024:doi:10.1016/S2215-0366(24)00133-0.