Quetiapine 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. 

First, optimize current mood stabilizer or initiate mood-stabilizing medication lithium,0 valproate,0 or carba-mazepine0 Consider adding a benzodiazepine (lorazepam or clonazepam) for short-term adjunctive treatment of agitation or insomnia if needed Alternative medication treatment options carbam-azepine0 if patient does not respond or tolerate, consider atypical antipsychotic (e.g., olanzapine, quetiapine, risperidone) or oxcarbazepine. 

Ari pi prazole, olanzapine, quetiapine, risperidone, and ziprasidone are effective as monotherapy or as add-on therapy to lithium or valproate for acute mania. Prophylactic use of antipsychotics can be needed for some patients with recurrent mania or mixed states, but the risks versus benefits must be weighed in view of long-term side effects (e.g., obesity, type 2 diabetes, hyperlipidemia, hyperprolactinemia, cardiac disease, and tardive dyskinesia). 

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... 

Until recently, lithium carbonate was the universally preferred treatment for bipolar disorder, especially in the manic phase. With the approval of valproate, aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone for this indication, a smaller percentage of bipolar patients now receive lithium. This trend is reinforced by the slow onset of action of lithium, which has often been supplemented with concurrent use of antipsychotic drugs or potent benzodiazepines in severely manic patients. The overall success rate for achieving remission from the manic phase of bipolar disorder can be as high as 80% but lower among patients who require hospitalization. A similar situation applies to maintenance treatment, which is about 60% effective overall but less in severely ill patients. These considerations have led to increased use of combined treatment in severe cases. After mania is controlled, the antipsychotic drug may be stopped and benzodiazepines and lithium continued as maintenance therapy. 

Valproate + quetiapine fumarate III Bipolar I disorder AstraZeneca... 

Use in combination with lithium or valproate for the acute treatment of mania or mixed states (primarily with psychotic features) for bipolar I disorder. Only olanzapine is FDA approved at this time for maintenance treatment and only quetiapine for bipolar depression. 

I A small RCT showed that adding quetiapine to valproate is more effective than valproate alone for the treatment of mania in adolescents. 

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. ... 

Quetiapine Two patients with bipolar disorder developed delirium when prescribed quetiapine as an adjunct to valproate for acute mania the delirium resolved after quetiapine was discontinued [351 j. A pharmacodynamic interaction between these drugs was suspected. 

Huang CC, Wei IH. Unexpected interaction between quetiapine and valproate in patients with bipolar disorder. Gen Hosp Psychiatry 2010 32(4) 446.el-2. 

In a 2-year randomized double-blind study of the comparative efficacy of a mood stabilizer alone (lithium or valproate plus placebo) or a mood stabilizer added to quetiapine in 628 bipolar subjects, combination treatment resulted in fewer mood episodes (20%) versus a mood stabilizer alone (52%), and mania and depression were prevented to an equal degree [18 ]. 

Quetiapine and valproate In a 12-month comparison of quetiapine (mean dose 465 mg/day n = 22) and valproate (mean dose 720 mg/day n = 16) in patients with rapid-cycling bipolar disorder, orthostatic... 

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. 

The incidences of leukopenia and neutropenia have been evaluated retrospectively in 131 children and adolescents taking valproate, quetiapine, or the combination [377 ]. The combined incidences of neutropenia and/or leukopenia were 44%, 26%, and 6% with the combination, valproate monotherapy, and quetiapine monotherapy respectively. There were statistically significant differences in the incidences of neutropenia and/or leukopenia between quetiapine and valproate and between quetiapine alone and the combination. Leukopenia and neutropenia induced by valproate and quetiapine co administration are not rare and patients taking a combination of these drugs should be monitored. 

An 85-year-old woman with a schizoaffective disorder was given valproate 600 mg/day and after 4 days complained of muscle pain and weakness. Other medications were quetiapine 200 mg/day, nifedipine 10 mg/day, torsemide 10 mg/day, levothyroxine 75 micrograms/day, and acetylsalicylic acid 100 mg/day. There was a fivefold increase in myoglobin concentration (292 ig/l), a sixfold increase in creatine kinase activity (14 pmol/l), and slightly increased liver enzyme activities. The serum... 

Quetiapine One patient taking long-term valproate developed edema in both legs 7 days after the addition of quetiapine, which... 

Rahman A, Mican LM, Fischer C, Campbell AH. Evaluating the incidence of leukopenia and neutropenia with valproate, quetiapine, or the combination in children and adolescents. Ann Phar-macother 2009 43(5) 822-30. 

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