Olanzapine 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. 

Mood stabilizers (e.g., lithium, valproic acid, and carbamazepine) used as augmentation agents may improve labile affect and agitated behavior. A placebo-controlled trial supports fast symptom improvement when divalproex is combined with either olanzapine or risperidone. 

Agitation (chronic) Sodium divalproex Risperidone Olanzapine SSRI Trazodone Ziprasidone Haloperidol... 

In the Expert Consensus survey (Rush and Frances, 2000), respondents were asked to rate which classes of medication may be helpful for treating patients with severe and persistent physical aggression and those who destroyed property. The atypical antipsychotics were rated most highly, followed by anticonvulsant/ mood stabilizer. These were followed (with much lower priority) by antidepressants and beta-blockers. Among the atypical antipsychotics, risperidone was rated most highly, followed by olanzapine others had much lower ratings. Divalproex or valproic acid and carbamazepine were rated highest of the mood stabi-... 

Tohen. M.. Baker. R.W., Milton. D.R., et al. Olanzapine versus divalproex sodium for the treatment of acute mama. Bipolar Disorders 3, 60-61, 2001. 

A 30-year-old man developed neuroleptic malignant syndrome after taking risperidone and lithium carbonate for 1 week, having previously been taking olanzapine and divalproex (637). 

Tohen M, Baker RW, Altshuler LL, Zarate CA, Suppes T, Ketter TA, Milton DR, Risser R, Gilmore JA, Breier A, Tollefson GA. Olanzapine versus divalproex in the treatment of acute mania. Am J Psychiatry 2002 159(6) 1011-7. 

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. 

A 67-year-old man with bipolar disorder became confused, delirious, and manic (99). His only medications were olanzapine 10 mg/day and divalproex sodium 500 mg bd. On day 6, typical neuroleptic malignant syndrome developed. He had a fever (39.9°C), obtundation, rigidity, tremor, sweating, fluctuating pupillary diameter, labile tachycardia and hypertension, hypernatremia, and raised serum creatine kinase. Olanzapine was withdrawn and the syndrome resolved by day 12. 

Revicki DA, Paramore LC, Sommerville KW, Swann AC, Zajecka JM. Divalproex sodium versus olanzapine in the treatment of acute mania in bipolar disorder health-related quality of life and medical cost outcomes. J Clin Psychiatry 2003 64 288-94. 

Hirschfeld RMA, Baker JD, Wozniak P, Tracy K, Sommerville KW. The safety and early efficacy of oral-loaded divalproex versus standard-titration divalproex, lithium, olanzapine, and placebo in the treatment of acute mania associated with bipolar disorder. J Clin Psychiatry 2003 64 841-6. 

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.). 

The efficacy and safety of olanzapine in disorders other than schizophrenia have been studied (SEDA-24, 67) (SEDA-25, 64) (SEDA-26, 61). In a 3-week, randomized, double-blind trial, the effects of a flexible dose of olanzapine (5-20 mg/day) and divalproex (500-2500 mg/day) for the treatment of patients with acute bipolar manic or mixed episodes have been compared (40). The olanzapine... 

In a 3-week double-blind study patients with mild to moderate mania were randomized to divalproex (n = 201 500-2500 mg/ day), olanzapine (n = 205 5-20 mg/day), or placebo (n = 105) [343 ]. Those who completed the first part of the study continued with a 9-week double-blind extension. Olanzapine was significantly more efficacious than placebo at 3 weeks and significantly more efficacious than divalproex at 12 weeks. Adverse effects caused withdrawal from the study in 13% (28/215) of those who took olanzapine and 9.5% (19/ 201) of those who took divalproex. Significantly more of those who took olanzapine reported weight increase and somnolence compared with divalproex or placebo. Significantly more of those who took divalproex reported nausea and insomnia compared with olanzapine. Those who took... 

Aaronson ST, Bardenstein L, Grecu-Gabos I, Tochilov V, Prelipceanu D, Oliff HS, Kryzhanovskaya L, Bowden C. Olanzapine versus divalproex versus placebo in the treatment of mild to moderate mania a randomized, 12-week, double-blind study. J Clin Psychiatry 2008 69(11) 1776-89. 

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