SUMMARYAims – To evaluate new generation antidepressants in relation to the placebo response. Methods – I review meta-analyses in which response to antidepressant medication and response to placebo were calculated. Results – All but one of these meta-analyses included unpublished as well as published trials. Most trials failed to show a significant advantage of SSRIs over inert placebo, and the differences between drug and placebo are not clinically significant for most depressed patients. Documents obtained from the U.S. Food and Drug Administration (FDA) revealed an explicit decision to keep this information from the public and from prescribing physicians. Conclusions – Because they do not incur drug risks, exercise and psychotherapy, which show at benefits at least equal to those of antidepressants, may be a better treatment choice for depressed individuals.Declaration of Interest: The author has not in the last 2 years received any support, including that from drug companies and honoraria for lectures and consultancies, from interests potentially in conflict with this work.