Aripiprazole Divalproex

Pharmacotherapy is the cornerstone of acute and maintenance treatment of bipolar disorder. Mood-stabilizing drugs are the usual first-choice treatments and include lithium, divalproex, carbamazepine, and lamotrigine. Atypical antipsychotics other than clozapine are also approved for treatment of acute mania. Lithium, lamotrigine, olanzapine, and aripiprazole are approved for maintenance therapy. Drugs used with less research support and without Food and Drug Administration (FDA) approval include topiramate and oxcarbazepine. Benzodiazepines are used adjunctively for mania. 

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. 

Paradoxical worsening of a schizoaffective disorder occurred in a 50-year-old man taking quetiapine 400 mg bd and divalproex 1000 mg bd, who was also given aripiprazole 15 mg/day. He recovered after withdrawal of aripiprazole and responded best to divalproex and olanzapine. 

Although presently only lithium, valproic acid/divalproex, and several atypical antipsychotics have been approved by the FDA as treatments for acute mania, clinicians prescribe a number of other medications as well for patients in the manic phase (Table 3.20). The strength of the data justifying their use varies, with the strongest evidence occurring with lithium and followed by atypical antipsychotics (aripiprazole, olanzapine, etc.). 

Aripiprazole 30 mg daily was given to 6 healthy subjects for 5 weeks, with valproate semisodium (divalproex sodium) daily in doses to achieve a serum valproate level of 50 to 125 mg/L, for weeks 3 to 5 of the study. The mean AUC and maximum plasma concentrations of aripiprazole were found to decrease by 24% and 26%, respectively, and the time to maximum aripiprazole levels was extended by 2 hours. Since aripiprazole and valproate share the same protein binding sites, it was considered likely that the valproate displaced bound aripiprazole leading to increased... 

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