One measure of a treatment's effectiveness is the regularity with which it proves superior to placebo. That measure also tells us about the consequences of using a treatment as a standard against which to test a new agent. To assess the frequency with which approved and presumably effective antidepressants and anxiolytics show statistical superiority over placebo, we reviewed placebo-controlled clinical trials of antidepressants and anxiolytics in a singularly large database free of publication bias. We evaluated clinical-trial data from the nine antidepressants approved by the FDA between 1985 and 2000. These trials comprised 10030 depressed patients who participated in 52 antidepressant clinical trials evaluating 93 treatment arms of a new or established antidepressant. Similarly, we examined clinical trials data from the 13 anxiolytics approved by the FDA between 1985 and 2000. These trials comprised 8340 anxious patients, 40 anxiolytic clinical trials and 75 treatment arms of a new or established anxiolytic. Fewer than half (48%, 45/93) of the antidepressant treatment arms showed superiority to placebo. Among anxiolytics, 48% (36/75) of anxiolytic treatment arms showed superiority over placebo. These data suggest that conventional psychopharmacologic treatments for depression and anxiety are superior to placebo less than half the time and call into serious question the widely propagated notion that placebo controls can be dispensed with in clinical trials of these agents. Exclusion of placebo controls in favour of non-inferiority trials would result in a high likelihood that ineffective antidepressants and anxiolytics would be foisted on the public and, less dangerous but also problematic, that potentially effective agents would be missed.