by Michael Fumento

ew drugs inspire more animosity among people who don’t use them than Prozac and its antidepressant cousins. On the one hand, they’re derisively described as “happy pills,” capable of slapping a smiley face on anyone. Actually, decades of research have shown that only those suffering true clinical depression benefit from them. Even then, the pills merely bring patients up to the level of non-depressed persons.

A second, contradictory claim is that the pills don’t work at all, except psychosomatically. Every so often a researcher releases an analysis of clinical drug trials that purportedly shows that antidepressants are little more effective than placebos. It is little wonder that these analyses always reach the same conclusion, because they always use the same methodology and the same data source. These reports are not only as baseless as the “happy pill” attacks; they’re downright dangerous because they can encourage depressed people to quit taking their medicine.

The latest such analysis appeared recently in the American Psychological Association journal, Prevention and Treatment (July 15, 2002). Chiefly authored by University of Connecticut psychologist Irving Kirsch, it combined clinical trials of six different antidepressants. Kirsch’s conclusion was that “80 percent of the response to medication was duplicated in placebo control groups.” Given the potential side-effects of antidepressants, Kirsch opined, “Medication might best be considered a last resort.” Several pundits then pumped out op-eds claiming that this same conclusion had been reached in an article by psychiatrist Arif Khan of the Northwest Clinical Research Center in Bellevue, Washington—notwithstanding that neither the article nor even a promotional press release about it had appeared at the time.

To turn to what has been published, however, Kirsch’s analysis is so filled with problems that it’s downright depressing in itself. One Godzilla-sized clue that something is terribly wrong with his conclusion is that the trials he lumped together, when looked at individually, show that the various antidepressants themselves are fairly consistent with each other in how well they treat various facets of depression. What changes from study to study is the efficacy of the placebo.

How can this be?

The difference between the drug and the placebo is greatly determined by several factors, including the intensity of the depression, the duration of the illness, and even the length of the clinical trial itself.

“At the milder end of depression, that without mania or mood-swings, you get about a 40 percent response rate [signifying effectiveness] for placebos,” notes Steven Dubovsky, professor of psychiatry at the University of Colorado Medical School, Denver. “But if you look at psychotic depression, the response rate is zero. For other severe forms and for chronic depression, the response rate is also very low,” he told me. Dr. Khan himself, in a commentary in the February 2002 Journal of Clinical Pharmacology, stated this: “The frequency of statistically significant differences between antidepressants and placebos was higher in the trials that included patients with more severe depression,” he wrote.

This completely refutes Kirsch’s conclusion, because the worst-off patients are generally kept out of clinical trials. “You cannot participate if you’re suicidal, because people think it’s unethical to give placebos to people who might kill themselves,” explains Dr. Dubovsky. “They also usually exclude anybody with concomitant illness, extreme depression, and chronic depression.”

Also exaggerating the apparent placebo effect is the fact that the studies define “response rates” as an improvement of at least 50 percent. “But who goes to the doctor for a 50 percent improvement?” asks Dr. Dubovsky. The higher the threshold for defining “improvement,” the more effective the antidepressants look.

Michael Fumento is a senior fellow at Hudson Institute in Washington, D.C. His latest book is BioEvolution: How Biotechnology Is Changing Our World (Encounter Books).

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