Issue date: Jan 3, 1999

A drug that blocks "substance P" offers new hope for the depressed

In this article:
4 ways to avoid antidepressant side effects
Back to "Brain index"

For depressed patients, there's more reason than ever to keep hope alive. The first really new antidepressant in decades - with very few side effects - could be in general use early in the next century.

The question of side effects is no small matter. Some patients choose to live with depression rather than endure the insomnia, nausea, sexual problems and other side effects they can cause.

Standard antidepressants - pioneered in the 1950s - all work by manipulating levels of "monoamine" brain chemicals such as serotonin, dopamine and norepinephrine. But Merck's trial drug MK-689 targets "substance P," a compound found throughout the human body and appearing to play a role in the perception of mental anguish.

In tests, MK-689 had "robust" antidepressant effect equal to the popular drug Paxil with far fewer side effects (only 3 percent of MK-689 patients reported sexual dysfunction, vs. 26 percent on Paxil).

Today's big three antidepressants are Prozac, Paxil and Zoloft, chemical cousins that also benefit anxiety, obsessive-compulsive disorder (OCD) and bulimia.

But they frequently cause nausea, headaches, sleep disruption and sexual dysfunction.

As a staff psychiatrist at Staunton Clinic in sub-urban Pittsburgh, Patty Gillespie has found ways to juggle side effects for her patients. Check with your doctor to see if these tactics are appropriate for you.

Try a time change. Patients who take drugs in the morning sometimes lose side effects if they take the drugs at night, or vice versa.

Try a switch. Because of slight chemical differences, a patient suffering side effects on Prozac may do better on Zoloft or Paxil. Another good first-line antidepressant can be Wellbutrin.

Try something new and fine-tuned. Two new selective serotonin reuptake inhibitors, or SSRIs - Luvox and the just-approved Celexa - seem to cause fewer side effects, although the jury is still out. Two other new drugs, Effexor and Serzone, appear less likely to cause sexual dysfunction but have their own drawbacks. Now in early tests: a purer Prozac, R-fluoxetine, that is expected to have fewer side effects than today's Prozac.

Try a combination. A main antidepressant and a secondary drug may shrink side effects. For example, if Prozac helps depression but causes insomnia, a low bedtime dose of the antidepressant Trazadone may give relief.

By Jim Thornton
Thornton received a 1998 National Magazine Award for health reporting.