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The use of valproate among patients with schizophrenia has increased, with one report indicating that over a third received valproate during hospitalization (Citrome et al. 2000; Wassef et al. 2000, 2001). A 4-week randomized, double-blind study of 242 schizophrenic patients who received risperidone or olanzapine alone, or divalproex plus the antipsychotic drug, indicated significantly greater improvement in Positive and Negative Syndrome Scale (PANSS)—Total and PANSS positive subscale scores among combination therapy patients from day 3 through day 21, but not at day 28. Platelet count was lower with combination therapy, and cholesterol levels increased with olanzapine or risperidone, compared with the significantly lower levels seen with antipsychotic plus divalproex. Weight gain did not differ between olanzapine and divalproex plus olanzapine; weight gain was greater with divalproex plus risperidone (7.5 pounds) than with risperidone (4.2 pounds) (Casey et al. 2003). A small (n = 12) randomized, blinded study also indicated greater global improvement and improvement in negative symptoms for patients who were receiving divalproex plus haloperidol than for those who were receiving haloperidol alone (Wassef et al. 2000). Divalproex appeared to be effective as adjunctive therapy for schizoaffective disorder in a retrospective study of 20 patients with schizoaffective disorder, bipolar type (Bogan et al. 2000).

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