Understanding the true incidence and severity of antidepressant discontinuation symptoms is important because misconceptions may influence prescribing practices, patient adherence, and add unnecessary fear around stopping treatment.

A recently published study aimed to clarify whether patients who discontinue antidepressants experience clinically meaningful withdrawal symptoms compared to those continuing antidepressants or stopping placebo. This large-scale meta-analysis from 50 randomized controlled trials (n = 17,828) quantified the incidence and nature of antidepressant discontinuation symptoms using standardized measures (e.g., Discontinuation-Emergent Signs and Symptoms [DESS] scale). Participants included individuals with major depressive disorder, anxiety disorders, and related conditions.

Results showed that, on average, individuals who discontinued antidepressants experienced one additional discontinuation symptom (SMD 0.31) at one week of cessation compared to those continuing medication or stopping placebo. However, this level of symptoms was below the clinical threshold for discontinuation syndrome (defined as =4 symptoms on the DESS). The most common symptoms were vertigo (OR 6.40), dizziness (odds ratio, OR 5.52), nausea (OR 3.16), and nervousness (OR 3.15).

Importantly, there was no association between discontinuation and mood worsening, supporting the idea that relapse and withdrawal are distinguishable. Desvenlafaxine, venlafaxine, and duloxetine were associated with the highest rates of symptoms, particularly dizziness, whereas vortioxetine and fluoxetine showed relatively low risk. Tapering did not significantly reduce symptom burden compared to abrupt cessation in short-duration tapers.

These findings challenge prevailing assumptions about the frequency and clinical severity of antidepressant withdrawal. For mental health clinicians, particularly those managing SSRI or SNRI discontinuation, the results support a balanced approach: while discontinuation symptoms are real and identifiable, they are often transient and mild. The need for prolonged tapering strategies may be overstated in the absence of other risk factors. Clinicians should monitor for relapse while avoiding unnecessary reinforcement of nocebo effects.

Reference:
Kalfas M et al. JAMA Psychiatry. 2025 Jul 9:e251362. Abstract.