Quetiapine and valproate

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

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... 

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. 

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 ]. 

Hung WC, Hsieh MH. Neutropenia associated with the comedication of quetiapine and valproate in 2 elderly patients. J CUn Psychopharmacol 2012 32(3) 416-7. 

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. 

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. 

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. 

First, initiate and/or optimize mood-stabilizing medication lithium " or valproate or atypical antipsychotic (e.g., olanzapine, quetiapine, risperidone) Alternative anticonvulsants carbamazepine, lamotrigine, or oxcarbazepine... 

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. ... 

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 ]. 

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... 

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. 

---