Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration

Summary & key facts

This meta-analysis used clinical-trial data submitted to the US Food and Drug Administration, including unpublished studies. It found that the average difference between antidepressants and placebo was small (about 1.8 points on the Hamilton Rating Scale of Depression). Drug–placebo differences grew as initial depression severity increased, but that rise was due to weaker placebo responses in the most severely depressed patients, not to stronger drug effects. Only patients at the extreme upper end of severity reached a 3-point difference that some guidelines treat as clinically meaningful.

Key facts:

• The overall mean drug–placebo difference across the FDA trials was 1.80 points on the Hamilton Rating Scale of Depression (HRSD).
• The UK’s National Institute for Clinical Excellence (NICE) has used a 3-point HRSD difference as a criterion for clinical significance; the observed mean difference (1.80) is below that threshold.
• Drug–placebo differences increased with higher baseline severity: there was virtually no difference at moderate severity and a relatively small difference for very severe depression.
• The rise in drug–placebo difference with severity was attributable to decreased responsiveness to placebo among very severely depressed patients, rather than increased responsiveness to medication.
• The authors obtained FDA files that identified 47 clinical trials for these antidepressants; the dataset included both published and unpublished trials to reduce reporting bias.
• Most trials were short (commonly 6 weeks), used adults diagnosed with major depressive disorder, and analyzed outcomes using last observation carried forward (LOCF) methods.

Abstract

Drug-placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication.

Topics

Mental Health Research Topics Pain Management and Placebo Effect Treatment of Major Depression

Categories

Cognitive Neuroscience Life Sciences Neuroscience

Tags

Alternative medicine Antidepressant Clinical trial Depression (economics) Drug Economics Hippocampus Internal medicine Macroeconomics Medicine Meta-analysis Pathology Placebo Psychiatry

Substances

Other

Conditions & symptoms

Depression Lack of energy or motivation Poor sleep Sadness or low mood