Tamoxifen - Serendipity for Bipolar Disorder?

[Andi]

by Kimberly Bailey
Tamoxifen, an anti-estrogen drug, has been an active player on the field of breast cancer treatment for more than 20 years. It is prescribed as treatment for advanced breast cancer as well as therapy for early stage breast cancer following surgery or radiation therapy. It is also currently being used as a preventative measure in women at high risk for breast cancer (National Cancer Institute). It is in this area that many studies are currently being conducted, and from these studies, a serendipitous treatment for mania in those with bipolar disorder may have been found.

Tamoxifen blocks estrogen receptors. Therefore, it is effective in treating women whose breast cancer has lots of estrogen receptors. However, clinicians noted that to a degree women whose breast cancer does not have estrogen receptors also responded to treatment. How? Research has now found that Tamoxifen is also a protein kinase C inhibitor (Kruiper).

Protein kinase C is a signaling pathway within nerve cells. Perhaps a rather simplified way to understand its role is to view it as part of a very complex system for communication within a neuron. Protein kinase C "regulates how fast nodes fire; how much neurotransmitter is released. It brings about changes in gene expression, turning on and off genes that will come back to you" (Manji). (For more on neurotransmitters, see Messengers of the Brain.)

Husseini Manji, MD, Director of the Neuropsychiatric Research Unit at the Detroit Medical Center, along with other laboratories, had been investigating the effects of both lithium and depakote on the protein kinase C system. Dr. Manji has demonstrated that both these drugs bring about "very selective changes in protein kinase C in areas of the brain that we think are involved in manic-depressive illness" (Manji). Dr. Manji shared in a speech, "So we wondered if dampening protein kinase C was how these medications work in mania. If we had something that directly dampened protein kinase C, maybe it would be a new anti-manic medication. That's why we ran into a problem. There aren't very many medications available for human use which dampen protein kinase C" (Manji). In another article he adds, "When I heard that news (regarding the findings of Tamoxifen's action as a protein kinase C inhibitor), I decided to do a study using Tamoxifen in the treatment of mania" (Kruiper). Dr. Manji is now conducting research with human participants. 75% of those in the study are responding well to Tamoxifen as an anti-manic agent (Manji).

"Dr. Manji emphasizes that these are hopeful, but preliminary results. The study will be ongoing for several years, but so far has exciting implications. 'We’ve learned important clues about the involvement of PKC in bipolar disorder, and we’re also hopeful that because they can be used so safely and quickly that PKC inhibitors could be safely used in the Emergency Room to treat mania. We’re close to answering some very fundamental and important questions about the illness' " (Kruiper).

More than 100 years ago doctors first noticed that lithium appeared to be useful in treating mood disorders while using it as a treatment for gout, and John Cade's re-discovery of lithium's role in controlling mania in 1949 was also the result of a fortuitous accident. Perhaps we will soon have reason again to thank researchers for being good observers, if Tamoxifen is proved to be an effective drug for bipolar disorder.


http://www.bipolar.about.com/library...0930a.htm?nl=1