With their curiosity piqued by evidence that inhibition of protein kinase C (PKC) could potentially have anti-manic effects, a group of researchers from the NIMH, NIH, and HHS set up a small experiment to test how tamoxifen, a drug used in breast cancer treatment, might benefit those who experience bipolar disorder related mania. Sixteen subjects with bipolar disorder were randomly assigned to groups that either received tamoxifen or placebo for three weeks. They were surveyed, using the Young Mania Rating Scale, to assess their progression.
The group who received tamoxifen, which is the only known PKC inhibitor capable of crossing the blood-brain barrier, faired dramatically better than the placebo group. 63% of the drug group responded positively, with reduced scores on the Young Mania Rating Scale, while only 13% of the placebo group showed improvement. As the Psychiatric Times noted though, the size of the improvement was even more stunning:
The tamoxifen group showed a decrease of 18.3 points from baseline to endpoint on the Young Mania scale, while the placebo patients' mania worsened 4.7 points. These findings support the results of an earlier single-blind study and that of other recent studies with tamoxifen, the researchers said.
The tamoxifen also proved to work quickly, with onset occurring within five days of the beginning of treatment. For the research team, these results show a great deal of promise and should precipitate a larger study that may serve to highlight any other issues not discovered in small trials.
Tamoxifen, as a relatively selective PKC, provides an excellent look at how PKC inhibition may influence mania, especially in bipolar individuals. Unfortunately, tamoxifen is not a solution in and of itself. As a powerful cancer drug, tamoxifen has a number of side effects, particularly when used long-term, that make it unfeasible for this type of treatment. What tamoxifen does do though, is point toward a new solution for those researching psychopharmacological responses to mania. By illuminating a new piece of the neuro-physiological puzzle, this research should lead to better innovations and more targeted treatments for this disorder.
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