Placebo Effect in Depression

To the Editor: Drs. Mathew and Charney (1) provided a very informative commentary on publication bias and antidepressant efficacy. They made clear that the modest advantage of drug over placebo in reported clinical trials is reduced when unreported clinical trials are included in data analysis. The robust placebo response, particularly in less severely depressed subjects, deserves emphasis when considering clinical implications. A negative view is that the moderate effect size suggests that the advantages of drug treatment may not be worth the costs in many instances and antidepressant drugs should be more restricted to severe cases. An alternative view is that the placebo effect has substantial clinical benefit. Aspects of the placebo response may be associated with psychosocial therapeutics, but for many patients (e.g., primary care) prescription of antidepressant medication is the only effective means of providing the placebo effect (with whatever additional active drug effect may be present). The critical comparison for efficacy requires placebo, but the critical comparison for clinical effectiveness is a no-treatment control.