- Apr 16, 2008
Does anyone here see a psychiatrist for bipolar disorder whom keeps them unmedicated?
Or minimally medicated?
Or minimally medicated?
Arch Gen Psychiatry. 2008 Mar;65(3):255-63.
Protein kinase C inhibition in the treatment of mania: a double-blind, placebo-controlled trial of tamoxifen.
Yildiz A, Guleryuz S, Ankerst DP, Ongür D, Renshaw PF.
Department of Psychiatry, Dokuz Eylül University, Huzur Mah, Saffet Baba Sok, No. 27/12 PK: 35320 Narlidere, Izmir, Turkey. [email protected]
CONTEXT: Findings that protein kinase C (PKC) activity may be altered in mania, and that both lithium carbonate and valproate sodium inhibit PKC-associated signaling in brain tissue, encourage development of PKC inhibitors as candidate antimanic agents. OBJECTIVE: To perform a controlled test of antimanic efficacy of the centrally active PKC inhibitor tamoxifen citrate. DESIGN: Three-week, randomized, double-blind, placebo-controlled, parallel-arms trial. SETTING: A university medical center inpatient psychiatric unit in Izmir, Turkey. PATIENTS: Sixty-six patients aged 18 to 60 years, diagnosed as having DSM-IV bipolar I disorder on the basis of the Structured Clinical Interview for DSM-IV, currently in a manic or mixed state, with or without psychotic features, with initial scores on the Young Mania Rating Scale (YMRS) greater than 20. INTERVENTION: Treatment with tamoxifen or identical placebo tablets for up to 3 weeks. Adjunctive lorazepam was allowed up to 5 mg/d. MAIN OUTCOME MEASURES: Primary: change in YMRS scores; secondary: change in Clinical Global Impressions-Mania scores, weekly ratings of depression and psychosis, and adjunctive use of lorazepam. RESULTS: The 21-day trial was completed by 29 of 35 subjects randomized to receive tamoxifen (83%) and 21 of 31 given placebo (68%) (P = .25). Intent-to-treat analysis of available measures on all 66 subjects indicated that tamoxifen treatment yielded mean decreases in scores on the YMRS and Clinical Global Impressions-Mania of 5.84 and 0.73 point per week, respectively, compared with mean increases of 1.50 and 0.10 point per week, respectively, with placebo; both drug-placebo contrasts differed significantly (P < .001). CONCLUSIONS: Tamoxifen demonstrated antimanic properties and was remarkably well tolerated. The findings encourage further clarification of the role of PKC in the pathophysiologic mechanism of bipolar I disorder and development of novel anti-PKC agents as potential antimanic or mood-stabilizing agents. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00411203 and isrctn.org Identifier: ISRCTN97160532.
Nope, the study I've posted is confirmation -- it IS a repeated study. The original pilot study was done in 2000. This is the original follow-up done by a prestigious, peer-reviewed journal that confirms proof of concept.Your tamoxifen link is inconclusive. It charts a small study that doesn't seem to have been repeated and just because it's on pub med doesn't make it good science it just means it's science and it doesn't necessarily mean that's it a breakthrough drug. There is mention of anti manic properties but none of anti depression and any mood stabiliser has to work from both ends of the spectrum.
Mol Psychiatry. 2002;7 Suppl 1:S46-56.
PKC, MAP kinases and the bcl-2 family of proteins as long-term targets for mood stabilizers.
Manji HK, Chen G.
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, MD 20892, USA. [email protected]
The complexity of the unique biology of bipolar disorder--which includes the predisposition to episodic, and often progressive, mood disturbance--and the dynamic nature of compensatory processes in the brain, coupled with limitations in experimental design, have hindered our ability to identify the underlying pathophysiology of this fascinating neuropsychiatric disorder. Although we have yet to identify the specific abnormal genes in mood disorders, recent studies have implicated critical signal transduction pathways as being integral to the pathophysiology and treatment of bipolar disorder. In particular, a converging body of preclinical data has shown that chronic lithium and valproate, at therapeutically relevant concentrations, regulate the protein kinase C signaling cascade. This has led to the investigation of the antimanic efficacy of tamoxifen (at doses sufficient to inhibit protein kinase C), with very encouraging preliminary results. A growing body of data also suggests that impairments of neuroplasticity and cellular resilience may also underlie the pathophysiology of bipolar disorder. It is thus noteworthy that mood stabilizers, such as lithium and valproate, indirectly regulate a number of factors involved in cell survival pathways--including cAMP response element binding protein, brain derived neurotrophic factor, bcl-2 and mitogen-activated protein kinases--and may thus bring about some of their delayed long-term beneficial effects via under-appreciated neurotrophic effects. The development of novel treatments, which more directly target molecules involved in critical central nervous system cell survival and cell death pathways, has the potential to enhance neuroplasticity and cellular resilience, thereby modulating the long-term course and trajectory of these devastating illnesses.
PMID: 11986995 [PubMed - indexed for MEDLINE]
No, actually. My original question still stands:It seems that you don't want lithium or SV and want someone to give you something different. Sorry but we can't do that here - we're not doctors or psychiatrists.
Did you even look at the studies I posted? 3 out of the last 4 were done in the United States. All 5 studies I posted qualify as empirical evidence.I'm not taking it personally but perhaps I should make my feelings a little clearer? I'm not interested in a discussion and I am unconvinced unless I see a little more empirical evidence and some that has been carried out in this country. That's not taking it personally it's just a refusal to get into a discussion.
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