CAMBRIDGE, Mass.--On July 6, Sarafem (fluoxetine hydrochloride) became the first prescription drug approved by the U.S. Food and Drug Administration for treating mood swings and physical symptoms associated with a severe pre-menstrual condition called premenstrual dysphoric disorder (PMDD). This use of the drug, also known as Prozac, and other serotonin-uptake blockers was studied and patented by Massachusetts Institute of Technology researchers.
The FDA gave Indianapolis-based Eli Lilly and Co., which developed Prozac, the rights to market Sarafem for PMDD, which affects 3 to 5 percent of menstruating women in the United States. In November 1999, a FDA advisory committee recommended that the drug should be used to treat women whose symptoms are severe enough to interfere with daily social and professional functioning. The drug is expected to be available in pharmacies in August.
In the 1970s, Richard Wurtman, C. H. Green Distinguished Professor at MIT and director of MIT's Clinical Research Center (CRC), and colleagues first showed that eating carbohydrates raises brain serotonin levels. Serotonin affects mood and appetite. Judith Wurtman, research scientist in MIT's Department of Brain and Cognitive Studies, later showed that women with PMS overeat carbohydrates and gain weight. She speculated that this overeating increases brain serotonin, which diminishes feelings of depression and anger. This was the first suggestion that some PMDD and PMS symptoms might be caused by inadequate brain serotonin.
The Wurtmans tested this theory by giving affected women sertonin uptake blockers such as Prozac, which increases brain serotonin, or special mixtures of dietary carbohydrates. Both methods improved symptoms. MIT patented the use of Prozac and other related drugs to treat severe PMDD. Judith Wurtman also invented PMS ESCAPE, a dietary supplement, to treat mild PMS.
"We discovered that women with PMS can gain weight because they crave and overeat carbohydrates, often in conjunction with foods that are high in fat," Judith Wurtman said. "The carbohydrates raise serotonin levels in the brain and relieve anger, depression and hostility.
"Apparently, women are using carbohydrate-rich foods like a drug," she said.
Those suffering from mild PMS as well as PMDD experience a range of emotional and physical symptoms a week or two before getting their periods. Unlike run-of-the-mill PMS, PMDD is severe enough to interfere with patients' lives at home or work.
For a PMDD diagnosis, a woman must have, in addition to monthly episodes of depression, tension, mood swings and irritability, symptoms such as decreased interest in usual activities, difficulty concentrating, lethargy, marked change in appetite, insomnia or hypersomnia and physical symptoms such as breast tenderness or abdominal bloating.
In two double-blind placebo-controlled studies, Sarafem drug was significantly more effective than a placebo in helping mood, physical and social impairment symptoms.
MIT licensed the use of serotonin uptake blockers like Prozac for treating PMS/PMDD to Interneuron, a Lexington, Mass.-based drug company founded by Richard Wurtman. Subsequently, Interneuron sub-licensed this patent for Prozac, now called Sarafem, to Eli Lilly. A portion of Interneuron's royalties on future sales of Sarafem will be passed on to MIT. Using a new trademark, Sarafem, for the drug will help Lilly launch a public education campaign on the differences between depression and PMDD.
Researchers have speculated that normal hormonal changes may trigger a serotonin deficiency in some people, causing PMDD. Prozac is currently marketed for the treatment of depression, obsessive-compulsive disorder and bulimia.