Posts Tagged ‘SSRI’

What’s MDD?

March 1st, 2013

I chaired the APA workgroup that authored the third edition of the treatment guideline for major depressive disorder (MDD), published at the end of 2010. MDD is a typical DSM-3 (and beyond) diagnostic category—a behavioral syndrome, which doubtlessly encompasses many biologically distinct diseases. (Hence the varied responses of patients to our ministrations.) But even while we eagerly await the dawning of the era of personalized, genomically informed medicine in psychiatry, we can still assess each depressed patient with a careful differential diagnosis—considering substance abuse, medical and neurologic diseases, and personality disorders, among other possibilities.

This came to mind when a resident presented a case to me. The chief complaints were lack of energy and interest—certainly key components of MDD, but easily reflecting a host of other diagnoses. When I saw the middle-aged man, he had mask-like facies, bradykinetic features, and a resting tremor. On examination he displayed muscular rigidity. We referred the patient to a neurologist, who confirmed a diagnosis of Parkinson disease. The patient’s psychiatric complaints responded favorable to the antiparkinson regimen, as did his motor signs. We will soon taper his SSRI. It didn’t take long, and it sure helped this man.

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

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.
Editor,
Biological Therapies in Psychiatry
Professor and Chair, Psychiatry, Penn State University
Editor-in-Chief,
Journal of Clinical Psychiatry