Antidepressants vs Placebo: Why the Gap Is Narrowing in Modern Trials
Why do modern antidepressants show smaller benefits over placebo?
Modern antidepressants show smaller benefits because clinical trials have changed - broader patient selection and different study designs have reduced the drug-placebo difference. Early trials with severely ill hospitalized patients showed larger effects. Key factors:
- Broader patient selection - less severely ill patients included in modern trials
- Changed study designs - regulatory and methodological changes affect results
- Higher placebo response - placebo effects have increased over time
- Different patient populations - early trials focused on more severely ill patients
A comprehensive overview published in World Psychiatry reveals that while early antidepressant trials with severely ill, hospitalized patients showed substantial drug-placebo differences, these robust differences have not held up in trials of the past couple of decades. The narrowing of the drug-placebo difference has been attributed to fundamental changes in clinical trial conduct, including broader diagnostic criteria and regulatory influences.