One in 7 Patients Experience Antidepressant Discontinuation Symptoms, Study Says

Including non-specific effects, approximately 15% or 1 in 6 to 7 patients experience antidepressant discontinuation symptoms, according to recent systematic review and meta-analysis results published in The Lancet Psychiatry. 

“Our findings suggest that imipramine, paroxetine, and desvenlafaxine and venlafaxine are associated with a higher risk of severe antidepressant discontinuation symptoms compared with other antidepressants,” noted lead author Jonathan Henssler, MD, University of Cologne, Germany, and co-authors, “although we only found small differences between individual antidepressive agents, possibly a manifestation of relevant non-pharmacological effects.”

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Researchers searched Medline, EMBASE, and CENTRAL from their inception until October 13, 2022, for randomized controlled trials (RCTs), other controlled trials, and observational studies that examined the incidence of antidepressant discontinuation symptoms. Eligible studies investigated the cessation or tapering of established antidepressants or placebo in participants with any mental, behavioral, or neurodevelopmental disorder, excluding antipsychotics, lithium, or thyroxine. Researchers excluded studies on neonates or those using antidepressants for physical conditions. Data from the selected studies were pooled in random-effects meta-analyses after summary data extraction and a risk of bias evaluation. 

From 6095 screened studies, 79 (44 RCTs and 35 observational) covering 21,002 patients (72% female; mean age 45 years) were selected. Of the included patients, 16,532 discontinued an antidepressant and 4470 discontinued a placebo. The incidence of at least 1 discontinuation symptom was 0.31 (95% CI 0.27–0.35) after stopping antidepressants, and 0.17 (0.14–0.21) after stopping placebo, with a summary difference of 0.08 between groups. Severe discontinuation symptom incidence occurred at 0.028 (0.014–0.057) for antidepressants and 0.006 (0.002–0.013) for placebo. Desvenlafaxine, venlafaxine, imipramine, and escitalopram were linked to higher frequencies of symptoms, while imipramine, paroxetine, and either desvenlafaxine or venlafaxine were linked to higher severity of symptoms.

“Evidence that about 1 in 35 patients suffers from severe antidepressant discontinuation symptoms must be considered preliminary at present, but caution towards severe antidepressant discontinuation symptoms seems to be warranted when discontinuing imipramine, paroxetine, or desvenlafaxine and venlafaxine,” authors concluded. 

Researchers noted that there is a lack of robust evidence on different dose reduction regimens (such as tapering) and their effect on discontinuation symptoms, which may be a limitation of this study. 

Reference
Henssler J, Schmidt Y, Schmidt U, et al. Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis. Lancet Psychiatry. 2024;11(7): 526-535. doi.org/10.1016/S2215-0366(24)00133-0