Posts Tagged ‘targeted treatment’

When mechanism matters

December 13th, 2010

Maprotiline (Ludiomil) is a tetracyclic antidepressant introduced in the early 1980s. It is a norepinephrine reuptake inhibitor, which is believed to be its primary mechanism of antidepressant action. It had a particularly high incidence of seizures, which the manufacturer initially minimized. Today maprotiline is seldom prescribed.

Initial advertising for maprotiline featured the headline, “When Mechanism Matters.” Perhaps the people who wrote the ad copy were banking on the Emperor’s-New-Clothes phenomenon: doctors would be too embarrassed to admit we didn’t know when mechanism mattered in selecting an antidepressant for a depressed patient. We still don’t.

We make assumptions. SSRIs work by enhancing serotonin. SNRIs work via both serotonin and norepinephrine. MAOIs work by inhibiting MAO. Perhaps these theories are valid; perhaps not. In theory, a patient who fails to respond to one SSRI should do better with a drug with a different mechanism of action, rather than a different SSRI. But the data say otherwise.

I am convinced that, ultimately, mechanism matters. And psychiatric patients are different one from the other. Someday we will understand the unique pathophysiology that underlies abnormal thinking, feeling, and behavior. Someday we will elucidate the various etiologies that distort normal brain function in these ways. And when that time comes, we will tailor treatments to the abnormalities: targeted treatments; personalized medicine.

But until that time, let’s not become gullible to those who peddle expensive new products with thinly veiled promises that understanding the receptor or other properties of a compound translates into real-life advantages. And remember that sales people are not only the companies’ marketers and representatives, but also some of our colleagues who write and lecture. A professor of mine admonished his students to be “therapeutic skeptics—but not nihilists.” Amen.

- Alan J. Gelenberg, M.D.
Biological Therapies in Psychiatry
Professor and Chair, Psychiatry, Penn State University
Journal of Clinical Psychiatry