May 7, 1999

For the first time, researchers are testing a skin patch as a delivery method for an antidepressant drug, the monoamine oxidase inhibitor selegiline, and the preliminary results from a multisite trial of the patch seem promising.

The final phase of the trial is not completed yet, but will be finished within the next few months. The results will have to be scrutinized and subjected to peer review, but the first-time use of the skin patch to administer antidepressant medication has drawn more attention than usual for a medication trial. The research is being funded entirely by Somerset Pharmaceuticals Inc., which manufactures selegiline. Company officials were not available for comment.

Alexander Bodkin, M.D., director of McLean Hospital's clinical psychopharmacology research program in Belmont, Mass, is the principal investigator for one of the trial sites. Although there are now many sites testing the patch with an estimated 700 participants, the initial research involving 177 participants took place at Belmont and five other locations in Pennsylvania, Kansas, Florida, and Washington State in 1997.

The results of that research, in which 89 patients received an active patch and 88 a placebo, were impressive, according to Bodkin. More than 70 percent of patients on the active patch experienced recovery from their depression, and many improved markedly within a week. Few showed any significant side effects, Bodkin said. The positive results led researchers to end the placebo arm of the trial after six weeks, with all participants then placed on the active patch for three months. The extended results were as impressive as the initial double blind, said Bodkin. Those recruited for the trial came from a cross-section of people with depression, not of people who failed to respond to other antidepressants.

In addition to efficacy and low toxicity, those on the patch did not experience one of the most troubling side effects of many antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs)-sexual dysfunction. MAOIs tend to enhance sexual function, Bodkin pointed out, so that result was not particularly surprising. In Europe selegiline is still prescribed to enhance memory and sexual function in the elderly, although in the U.S. it is approved by the FDA only to slow cognitive decline in people with Parkinson's disease.

Rex Cowdry, M.D., is a medical adviser to NAMI and former acting director of the National Institute of Mental Health.

"I'm always skeptical about reports of dramatic therapeutic advances and would want to see the study when it is completed. However, the patch is an interesting approach. It avoids highs and lows of drug levels in the blood, and it's possible that it would be a more acceptable way to take medication for at least some patients."

The history of advances in psychopharmacology has invariably involved identifying a problem to be overcome, be it a need for greater efficacy or a need to find a way around negative side effects, he added.

"Perhaps a patch developed to eliminate the side effects of MAOIs may prove to have much broader application. If this pans out, there are a number of reasons this might be a useful new strategy for medication administration."

A recent analysis by the federal Agency for Health Care Policy and Research (AHCPR) concluded that newer antidepressant drugs are not better than those used decades ago. MAOIs are among those drugs that have been around for many years, said Bodkin, and "have never been surpassed in efficacy." Administering the drug with a patch is like an intravenous injection without the needle, said Bodkin, meaning that the results occur more quickly than with oral medication. If the experience to date with the selegiline patch is borne out-and that is a big if-the method may provide a way of avoiding problems involving gastrointestinal absorption and dietary restrictions with other psychiatric drugs.

MAOIs are "more effective in a subgroup of patients, but in those patients they are completely effective," said Bodkin. "It is part of the street knowledge of psychopharmacology for years that the one form of antidepressant treatment for which patients were often extremely grateful was MAOI therapy."

While tricyclics and SSRIs are effective, with MAOIs it has been said that "patients experience their remission with delight," said Bodkin. Patients often say that it makes them feel revitalized, rather than merely able to cope.