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HARVARD GAZETTE ARCHIVES Depression Treated With Skin Patch
By William J. Cromie
Alexander Bodkin was startled when he first heard about the idea. There are good medicines to treat depression, and nicotine patches are effective for many people who want to stop smoking - why not put the two together and give antidepressants in the form of a skin patch?
"It seemed like a no-brainer," says the Harvard psychiatrist. "I wondered why no one had tried it."
So Bodkin and colleagues at six different medical centers decided to test the idea. They gave 89 patients an antidepressant called selegiline via a skin patch. At the same time, they gave another 88 patients a patch with no medication (a placebo) and then compared the two groups after six weeks.
"The results were stunning," according to Bodkin. "The patch worked, it worked rapidly, and we found no toxic side effects."
About three-quarters (72 percent) of those who received the drug felt much improved in only six weeks; many of them reported total improvement. "Some of the latter people couldn't even remember how it felt to be depressed," Bodkin comments.
After six weeks, everyone in the trial received the medicated patch for three months. "We studied this group too, and these individuals did very well," Bodkin notes.
To make sure depression patches work as well as they appear to, Bodkin and his colleagues have begun a longer study with more people. "I expect it will take two to three years before the patch is available by prescription," Bodkin says. "It could become the first-line drug against depression, an illness that strikes more than 19 million Americans a year, and is now the sixth leading cause of disability in the world. The potential is very exciting."
Remission with Delight
In the United States, approval by the Food and Drug Administration (FDA) should not be a problem, according to Bodkin; selegiline (Eldepryl) already is available in pill form. The skin patch works much faster than the pill because the drug goes directly into the bloodstream without having to be filtered by the liver.
Selegiline is a so-called monamine oxidase inhibitor (MAOI), a class of drugs considered the most effective for fighting depression. "MAOIs are well-known for the completeness and robustness of their response," Bodkin comments.
Prozac-like drugs can cause headaches, anxiety, apathy, insomnia, nausea, and loss of sexual interest. Selegiline is free of such side effects. Prozac-like drugs relieve distress but usually do not produce a feeling of well-being. Selegiline and other MAOIs often leave patients feeling elated for the first time, a condition sometimes referred to as "remission with delight."
The first of these drugs was discovered accidentally in 1952 by David Bosworth, an orthopedic surgeon in New York City. While trying to find a drug to relieve the bone and joint pain of tuberculosis, he experimented with a new antibiotic known as marsilid. Coincidentally, marsilid is also an MAOI.
Along with relief from tubercular pain, Bosworth noted that his patients developed a state of elation and a feeling of vitality. The patient is left, noted Bosworth, with "a normally optimistic instead of a depressed attitude."
Selegiline first caught the world's attention in the early 1960s under the name l-deprenyl. In Europe it was then known as a longevity pill. "Experiments with animals led to hopes that it would prolong life, memory, and sexual activity," Bodkin says. It didn't turn out that way, although selegiline is now used to help slow brain deterioration in people with Parkinson's disease.
Later in the 1960s, selegiline and other MAOIs fell into disuse when they were found to cause strokes and bouts of extremely high blood pressure in some people.
Researchers who investigated this problem discovered that all of the victims ate cheese on the day they took the drugs. Besides acting in the brain to restore a capacity for pleasure, MAOIs also affect the stomach and liver, reducing the organs' ability to remove toxins from some foods. "It's a cruel coincidence," Bodkin says. "The adverse reaction occurs because of a by-product of fermentation that's found in cheese, beer, and wine. To compound the problem, other foods, from chocolate to bananas, were added to the list of dangerous foods when in fact they didn't cause any toxic effects."
The FDA eventually allowed MAOIs to be reintroduced along with certain dietary restrictions. They have continued in use ever since, particularly by people who fail to benefit from other treatments.
More Testing
The FDA insisted that people in the skin-patch trial follow the MAOI diet. The participants were all tested and found to be moderately to severely depressed at the time of the study. The research took place at McLean Hospital, a Harvard-affiliated psychiatric facility in Belmont, Mass., where Bodkin works; at two sites in Philadelphia; and one each in Kansas, Florida, and Washington State.
"Many of the 89 people who received an active patch rather than the placebo enjoyed well-being of a type they had not felt before," Bodkin notes. "That's an improvement rarely seen with Prozac, Zoloft, and other antidepressants, and we saw results in only one week."
However, he continues, "our conclusions are tentative. We need to do more testing and analysis."
The FDA eliminated dietary restrictions for those in the new study, now getting under way. "When given through the skin, selegiline finally removes the need for such restrictions," Bodkin says.
One-half of the participants in this study will wear a medicated patch and half will wear a placebo for nine weeks. Afterwards, all those who complete the study will receive the drug and will be followed medically for several months.
"This trial, like the first, is exciting not only because it is testing a new delivery system for a powerful treatment of the most common psychiatric disease in the world," Bodkin says, "but because it is resurrecting the first family of antidepressants ever introduced - one that has never been surpassed in efficacy."
Copyright 1998 President and Fellows of Harvard College |
