Irving Kirsch, PhD

September 01, 2002

Antidepressants are widely believed to be exceptionally effective medications. The data, however, tell a different story. Kirsch et al. (2002a) analyzed the data sent to the U.S. Food and Drug Administration by the manufacturers of the six most widely prescribed antidepressants (fluoxetine [Prozac], paroxetine [Paxil], sertraline [Zoloft], venlafaxine [Effexor], nefazodone [Serzone] and citalopram [Celexa]). Their research showed that although the response to antidepressants was substantial, the response to inert placebo was almost as great. The mean difference was about two points on the Hamilton Rating Scale for Depression (HAM-D). Although statistically significant, this difference is not clinically significant (Jacobson et al., 1999). More than half of the clinical trials sponsored by the pharmaceutical companies failed to find significant drug/placebo difference, and there were no advantages to higher doses of antidepressants. The small difference between antidepressant and placebo has been referred to as a "dirty little secret" by clinical trial researchers (Hollon et al., 2002), a secret that was believed by FDA officials to be "of no practical value to either the patient or prescriber" (Leber, 1998, as cited in Kirsch et al., 2002b).