A meta-analysis of 22 studies of antidepressant outcome assessed the level of medication effects under conditions thought to be less subject to clinician bias than those in the typical double-blind drug trial. Studies were included only if, in addition to a newer antidepressant group, they also contained both standard antidepressant and placebo control groups. Effect sizes were quite modest and approximately one half to one quarter the size of those previously reported under more transparent conditions. Effect sizes that were based on clinician outcome ratings were significantly larger than those that were based on patient ratings. Patient ratings revealed no advantage for antidepressants beyond the placebo effect. Effect sizes were unrelated to sample sex ratios, patient age, inpatient or outpatient status, dosage level, and treatment duration. Findings highlight the fragility of the antidepressant effect.