Tamoxifen Helps Treat Bipolar Disorder

WEDNESDAY Sept. 12, 2007 -- The breast cancer drug tamoxifen helps control the manic phase of bipolar disorder, and works faster than many standard medications used to treat the chronic mental illness, a new study has found.

"One of the problems with existing treatments for bipolar disorder is they seem to have this long period before they start to work," explained Dr. Husseini K. Manji, senior study author and director of the U.S. National Institute of Mental Health's mood and anxiety disorders program.

Current treatments sometimes take weeks to become effective, Manji said. "And that obviously creates a huge problem," he said. When patients are in the manic phase, particularly, not getting relief fast enough from medication may mean they need to be hospitalized, he noted.

For the study, Manji and his colleagues gave eight patients experiencing a manic episode tamoxifen, while another eight received a placebo; no one knew which drug they were getting. After three weeks, 63 percent of those on tamoxifen had reduced symptoms of mania, compared to just 13 percent of those on a placebo. The tamoxifen group responded by the fifth day of treatment.

The study results are published online in the September issue of Bipolar Disorders.

Manji and his colleagues decided to study tamoxifen because they knew that standard medications used to treat mania are known to lower the activity of an enzyme called protein kinase C, or PKC, that regulates activities in brain cells. This enzyme is believed to become overactive when bipolar disorder patients experience a manic episode.

Tamoxifen also blocks PKC, but does it more directly than some bipolar drugs, according to the researchers.

Manji and his team made the discovery after years of searching for the correct cellular target to treat bipolar disorder, which affects almost 6 million American adults. Symptoms can be disabling, including profound mood swings, from depression to the manic phase, during which people can become overly excited and energetic but also irritable, before they plunge into depression again.

For the study, Manji said, "we started with 20 milligrams [of tamoxifen] a day. It was increased each day, usually up to 100 milligrams a day. "Literally at day five we saw this significant anti-mania effect," he said, adding that with standard medications it would have taken three weeks to see results.

"If we had something that would nip mania in the bud, it might save people from being hospitalized and getting sedating agents," Manji said.

A new bipolar drug would not be tamoxifen itself, he said, but rather another medicine that mimics what tamoxifen does in the brain. The development of such a drug would probably take at least five years before it could be approved for marketing, he said.

Dr. Gary S. Sachs, director of the bipolar clinic and research program at Massachusetts General Hospital and associate professor of psychiatry at Harvard Medical School, called the results "encouraging."

Sachs said he was aware of other research with similar findings. "I wouldn't say this study proves that tamoxifen works faster than standard [treatment,]" he said, since a head-to-head comparison was not done. But, while not definitive, "the study has important findings," he said.

Posted: September 2007


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