Antidepressant Trial Duration Versus Duration of Real-World Use: A Systematic Analysis.

Background: Antidepressant use is rising globally, with increasing duration of real-world prescribing. While the FDA considers 6-8 week trials adequate for regulatory approval, guidelines recommend prolonged treatment, raising questions about evidence supporting long-term prescribing practices.

Methods: This descriptive review analyzed 52 placebo-controlled randomized trials (n = 10,116) of the 10 most commonly prescribed antidepressants, sampled at 5-year intervals (1978-2023). We compared trial durations with real-world usage patterns from the National Health and Nutrition Examination Survey and assessed methodological characteristics including standardized scales, withdrawal monitoring, and taper protocols.

Results: The median duration of antidepressant use in the United States was approximately 5 years, while the median trial duration was 8 weeks (IQR: 6-12 weeks). Among trials, 88.5% (n = 46) lasted ≤12 weeks, 11.5% (n = 6) randomized participants beyond 12 weeks, and none exceeded 52 weeks. Few trials monitored withdrawal symptoms (3.8%), included taper protocols (18.9%), or reported post-treatment outcomes (1.9%).

Conclusions: A substantial discordance exists between the typical 8-week duration of clinical trials and the median 5-year real-world use of antidepressants. This gap, compounded by inadequate monitoring for withdrawal effects and post-treatment outcomes, raises important questions about the evidence supporting current long-term prescribing practices. Publicly funded trials of longer duration that include monitoring for withdrawal and relapse are necessary to determine optimal antidepressant therapy duration.