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Antidepressant discontinuation is one of the most contentious topics in psychiatry, fueling both patient fear and clinical uncertainty. But what does the highest quality, placebo-controlled evidence actually say? In this episode, we dive deep into the 2025 JAMA Psychiatry systematic review and meta-analysis by Kalfas et al. that re-examines the incidence and nature of discontinuation symptoms. We break down the study's striking headline finding—that stopping an antidepressant, on average, results in just one additional symptom compared to stopping placebo, a number below the threshold for clinically significant discontinuation syndrome. We discuss which symptoms, like dizziness , are pharmacologically real versus those that are not, and explore the paper's most critical clinical implication: its finding that early mood worsening is not associated with discontinuation, providing a data-driven framework for distinguishing withdrawal from true depressive relapse
By Stay updated on the foundational research shaping our field.Antidepressant discontinuation is one of the most contentious topics in psychiatry, fueling both patient fear and clinical uncertainty. But what does the highest quality, placebo-controlled evidence actually say? In this episode, we dive deep into the 2025 JAMA Psychiatry systematic review and meta-analysis by Kalfas et al. that re-examines the incidence and nature of discontinuation symptoms. We break down the study's striking headline finding—that stopping an antidepressant, on average, results in just one additional symptom compared to stopping placebo, a number below the threshold for clinically significant discontinuation syndrome. We discuss which symptoms, like dizziness , are pharmacologically real versus those that are not, and explore the paper's most critical clinical implication: its finding that early mood worsening is not associated with discontinuation, providing a data-driven framework for distinguishing withdrawal from true depressive relapse