Quetiapine Sodium valproate

Lithium, divalproex sodium (valproate), aripiprazole, olanzapine, que-tiapine, risperidone, and ziprasidone are currently approved by the FDA for treatment of acute mania in bipolar disorder. Lithium, olanzapine, and lamotrigine are approved for maintenance treatment of bipolar disorder. Quetiapine is the only antipsychotic that is FDA approved for bipolar depression. 

Calabrese JR, Bowden CL, Sachs GS, et al A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. Lamictal 605 Study Group. J Clin Psychiatry 64 1013-1024, 2003 Calabrese JR, Keck PE, Macfadden W, et al A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar 1 or 11 depression. Am J Psychiatry 162 1351-1360, 2005 Chen G, Manji HK, Hawver DB, et al Chronic sodium valproate selectively decreases protein kinase C alpha and epsilon in vitro. J Neurochem 63 2361-2364, 1994... 

Langosch JM, Drieling T, Biedermann NC, Born C, Sasse J, Bauer H, Walden J, Bauer M, Grunze H. Efficacy of quetiapine monotherapy in rapid-cycling bipolar disorder in comparison with sodium valproate. J Clin Psychopharmacol 2008 28(5) 555-60. 

Haematologic A case of quetiapine- and valproate-associated neutropenia and thrombocytopenia has been described after previous lamotrigine-induced Stevens-Johnson syndrome [226 ]. Two cases of neutropenia have been reported with the concomitant use of quetiapine and sodium valproate in elderly patients [227 ]. Another case of neutropenia in a 21-year-old male who was also on mirtazapine resolved following switch to ziprasidone is reported [228 ]. 

A randomised, placebo-controlled study in 191 patients found that quetiapine, combined with either lithium or valproate semisodium (divalproex sodium), was superior to lithium or valproate semisodium alone for treating bipolar mania. The incidence of extrapyramidal symptoms in patients receiving quetiapine with lithium or valproate semisodium was similar to those receiving placebo with lithium or valproate semisodium. No special precautions would therefore appear to be necessary on concurrent use. 

Analysis of plasma quetiapine levels of 94 patients, 9 of whom were also taking valproate, found a 77% increase in the concentration dose ratio compared with those patients not taking valproate. The US manufacturers report that valproate semisodium (divalproex sodium) increases the maximum plasma levels of quetiapine by 17%, and the UK manufacturers state that these changes are not clinically relevant. ... 

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