People think of the depressive phase of this brain disorder as the time of risk, but the manic phase has its own dangers, said NIMH Director Thomas R. Insel, MD. Being able to treat the manic phase more quickly would be a great asset to patients, not just for restoring balance in mood, but also because it could help stop harmful behaviors before they start or get out of control.
The three-week study included eight patients who were given tamoxifen and eight who were given a placebo (a sugar pill); all were adults and all were having a manic episode at the time of the study. Neither the patients nor the researchers knew which of the substances the patients were getting.
By the end of the study, 63 percent of the patients taking tamoxifen had reduced manic symptoms, compared with only 13 percent of those taking a placebo. Patients taking tamoxifen responded by the fifth day which corresponds with the amount of time needed to build up enough tamoxifen in the brain to dampen PKC activity.
The researchers decided to test tamoxifens effects on the manic phase of bipolar disorder because standard medications used to treat this phase, specifically, are known to lower PKC activity but they do it through a roundabout biochemical route that takes time. Tamoxifen is known instead to block PKC directly. As the researchers suspected would happen, tamoxifens direct actions on PKC resulted in much faster relief of manic symptoms, compared with some of the standard medications available today.
We now have proof of principle. Our results show that targeting PKC directly, rather than through the trickle-down mechanisms of current medications, is a feasible strategy for developing faster-acting medications for mania, said Manji. This is a major
|Contact: Susan Cahill|
NIH/National Institute of Mental Health