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Wiley InterScience | |||||||||||||||||||
  Bipolar DisordersVolume 9 Issue 6, Pages 561 - 570 Published Online: 5 Sep 2007 Erratum: Journal compilation © 2010 John Wiley & Sons A/S The Official Journal of The International Society for Bipolar Disorders
Abstract | References | Full Text: HTML, PDF (Size: 548K) | Related Articles | Citation Tracking  Original Article Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: a pilot study None of the co-authors of this study have any possible conflict of interest, financial or otherwise. Copyright 2007 Blackwell Munksgaard KEYWORDS antimanic • mania • protein kinase C • tamoxifen Zarate Jr CA, Singh JB, Carlson PJ, Quiroz J, Jolkovsky L, Luckenbaugh DA, Manji HK. Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: a pilot study. Bipolar Disord 2007: 9: 561–570. © Blackwell Munksgaard, 2007 ABSTRACTObjectives: 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 inhibition 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. Received 15 March 2007, revised and accepted for publication 11 May 2007 | 
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 | Personality and Mental Health |
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