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When Your Antidepressant Fails

© John McManamy

"Our first antidepressant amounts to scratch lotto in pill form."

It's time to revisit last year's Kirsch/Moore meta-analysis of 47 short-term clinical trials in the FDA database, which found the placebo in a virtual dead heat with six antidepressants. The findings represent the strongest case yet by those who believe that antidepressants are little more than placebos with side effects. In a guest lecture delivered at the University of Toronto in 2000, David Healy MD, director of the North Wales Department of Psychological Medicine at the University of Wales, observed: "If our drugs really worked, we shouldn't have three times the number of patients detained now compared with before, 15 times the number of admissions and lengthier service bed stays for mood and other disorders that we have now. This isn't what happened in the case of a treatment that works, such as penicillin ..."

If you are expecting a resounding rebuttal from the psychiatric establishment, you won't find it, perhaps because current practice anticipates initial failure. The American Psychiatric Association's Treatment Recommendations for Patients with Major Depressive Disorder suggests using another antidepressant from the same class should the first antidepressant fail, and then an antidepressant from a different class should the second antidepressant fail. The pioneering TMAP depression algorithm issued by Texas Department for Mental Health and Mental Retardation foresees a longer string of failures with six distinct options, ranging from switching drugs to combining them to augmenting them with other medications.

The few studies that we have to guide us indicate that serial trials are worth the effort, namely:

• A 1995 study found that of 113 patients who discontinued Prozac due to side effects, 71.8 percent were "much" or "very much" improved after eight weeks on Zoloft, with 9.8 dropping out due to adverse effects.
• A 1996 study found 28 of 55 patients who failed on their first SSRI had a "marked or complete antidepressant response" on their second SSRI.
• A 1997 study of 106 patients who either did not respond to Zoloft or were intolerant of the drug found 63 percent responded to Prozac.
• A 2001 study of 58 nonresponders to Prozac found 63 percent responded to Celexa after 12 weeks, with 18 percent dropping out.

A double-blind study published in the March 2002 Archives of General Psychiatry illustrates the benefit of switching across classes of antidepressants. Of 117 chronically depressed patients who failed to respond to Zoloft after 12 weeks and 51 patients with similar bad luck on imipramine, more than half from each group benefited from switching to the other.