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The Meaning and Influence of Time-Related Dropout Dynamics in Antidepressant Studies: Reassessing Current Approaches

There is an ongoing debate on the efficacy of antidepressants, fueling research that could have a significant impact on clinical practice. A recent meta-analysis on, as of yet, the largest corpus of antidepressant studies data came out suggesting much needed reference points to be used in informing stakeholders [1]. Despite the suggestion that the issue of clinical equipoise might finally be resolved, yet another intensification of the continuing debate on issues of clinical versus statistical significance, overall effectiveness, and cost- effectiveness of antidepressants ensued. The most important conclusion of this work, that antidepressants are more efficacious than placebo in adults with major depressive disorders, although backed by seemingly sound methodology, requires a more cautious approach considering significantly lower response rates to antidepressants in the placebo-controlled compared to head-to-head studies [1]. The authors of this synthesis of available evidence explain the issue through the possible influence of comparatively earlier active-group dropout in placebo-controlled studies, with participants dropping out early arguably having poorer responses, resulting in underestimation of the antidepressants’ true efficacy. This effect is mitigated by utilizing the last observation carried forward (LOCF) analysis.

depression, antidepressants, placebo, placebo effect, efficacy, randomized controlled trials

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