Source: New York Times
Date: 3 December 2002

Patch Raises New Hope
for Beating Depression


It was the first type of antidepressant, and for many people the monamine oxidase, or MAO, inhibitor remains the best hope for relief from major depression.

The trouble is that the side effects can be so serious that MAO inhibitors are rarely prescribed. When taken with certain foods, for example, they may bring on sudden and severe hypertension.

The problems, however, may soon be resolved.

A study reported in November in The American Journal of Psychiatry suggests that by administering the MAO inhibitor selegiline in patch form, patients can receive the antidepressant benefits of the drug without the usual side effects.

In research conducted at six sites, 42 percent of the subjects treated with the patch recovered from major depression within six weeks, and many showed great improvement much sooner. In the study, neither subjects nor researchers knew who had received the dummy medication.

One subject, requesting anonymity, told how his mood changed after a few weeks on the patch, saying: "It was like a switch had gone on. Before I had the patch, I couldn't function. Suddenly, I had a dramatic change in outlook. I could look forward to things."

Monamine oxidase is an enzyme found in the brain and in the digestive system. By inhibiting MAO in the brain, the antidepressant is believed to give patients a better supply of neurotransmitters to fight the symptoms of depression. Taken orally, however, the medication also blocks MAO in the digestive system, and that interferes with the detoxification of tyramine, a harmful byproduct of many aged foods.

Patients receiving MAO inhibitors are instructed to follow a tyramine-restrictive diet, which means no aged cheeses, no red wine, no soy sauce, no fermented foods and little or no alcohol. Eating tyramine-rich food while taking a MAO inhibitor can cause sudden and severe hypertension.

Delivering selegiline through the skin, however, changes the way the medication is absorbed. Rather than first being filtered through the intestines and liver, in patch form, the drug is aimed at the central nervous system.

"With this study we've demonstrated a way of getting an MAO inhibitor to the brain without interfering with the MAO in the digestive system," said the study's lead author, Dr. Alexander Bodkin of the clinical psychopharmacology research program of McLean Hospital in Belmont, Mass. The study was supported by the developers of the selegiline patch, Somerset Pharmaceuticals of Tampa, Fla.

While subjects in this study were instructed to follow a tyramine-restricted diet, in subsequent studies they were not.

Dr. Beverly McCabe, a professor of dietetics and nutrition at the University of Arkansas for Medical Sciences and a co-author of the "Handbook of Food and Drug Interaction," to be published in January, believes this form of drug delivery offers great promise. "I would think the risk of a tyramine reaction would be very low with transdermal selegiline," Dr. McCabe said. "The drug would absorbed into the bloodstream more evenly, which would also be beneficial."

Dr. Frederic Quitkin, director of the depression evaluation service at the New York State Psychiatric Institute in Manhattan, said, "MAO inhibitors are really great drugs: complicated to use, but extremely effective." As for the selegiline patch, he said, the research is encouraging. But he cautioned, "It will require further study to see how effective it is."

Another notable finding in the study of 177 patients was the 94 percent compliance rate for those on the selegiline patch. That is significant, said Dr. Bodkin, because compliance rates with oral antidepressants are typically much lower.

One side effect, in 36 percent of subjects, was a reaction, like redness or irritation, at the site of the patch. For most patients, Dr. Bodkin said, the irritation is minor compared with the side effects of most antidepressants.

The Good Drug Guide
The Secret of Happiness?
'New generation' MAOIs: EMSAM
Big Pharma and Madison Avenue
Antidepressant/dopamine D1 receptors
Transdermal selegiline (EMSAM): review
Transdermal selegiline (EMSAM): prospects
Transdermal selegiline without dietary restrictions
February 2006: EMSAM (transdermal selegiline) licensed by FDA
Transdermal selegiline preferentially inhibits MAO activity in brain