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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: a pilot study.

OBJECTIVES: Considerable preclinical biochemical and behavioral data suggest that protein kinase C inhibition would bring about antimanic effects. Notably, the structurally highly dissimilar antimanic agents lithium and valproate, when administered in therapeutically relevant paradigms, attenuate protein kinase C [corrected] function. There is currently only one relatively selective protein kinase C inhibitor that crosses the blood-brain barrier available for human use--tamoxifen. Our group recently conducted a single-blind study with tamoxifen in acute mania and found that it significantly decreased manic symptoms within a short period of time (3-7 days). In this study, we investigated whether antimanic effects can be achieved with a protein kinase C inhibitor in subjects with mania. METHODS: In a double-blind, placebo-controlled study, 16 subjects with bipolar disorder, manic or mixed, with or without psychotic features, were randomly assigned to receive tamoxifen (20-140 mg/day; n = 8) or placebo (n = 8) for three weeks. Primary efficacy was assessed by the Young Mania Rating Scale. RESULTS: Subjects on tamoxifen showed significant improvement in mania compared to placebo as early as five days, an effect that remained significant throughout the three-week trial. The effect size for the drug difference was very large (d = 1.08, 95% confidence interval 0.45-1.71) after three weeks (p = 0.001). At study endpoint, response rates were 63% for tamoxifen and 13% for placebo (p = 0.12). CONCLUSIONS: Antimanic effects resulted from a protein kinase C inhibitor; onset occurred within five days. Large, controlled studies with selective protein kinase C inhibitors in acute mania are warranted.[1]

References

  1. Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: a pilot study. Zarate, C.A., Singh, J.B., Carlson, P.J., Quiroz, J., Jolkovsky, L., Luckenbaugh, D.A., Manji, H.K. Bipolar. Disord (2007) [Pubmed]
 
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