1. ¹Portland VA Medical Center, Portland, OR, USA
2. ²George Washington University, Washington, DC, USA
3. ³Bioniche Development, Falls Church, VA, USA
4. ⁴HCPC-University of Texas, Houston, TX, USA
5. ⁵Abbott Laboratories, Abbott Park, IL, USA
6. ⁶University of Illinois, Chicago, IL, USA

Correspondence: DE Casey, Associate Director of Research, VISN 20 MIRECC (Mental Illness Research, Education and Clinical Center), Portland VA Medical Center (P3MIRECC), 3710 SW US Veterans Hospital Road, Portland, OR 97201, USA. Tel: +1 503 220 8262 ext 56477; Fax: +1 503 273 5211; E-mail: daniel.casey@med.va.gov

Received 10 January 2002; Revised 29 May 2002; Accepted 5 June 2002.

Abstract

This double-blind, randomized, multicenter study investigated the use of divalproex with an antipsychotic agent in patients hospitalized for acute exacerbation of schizophrenia. Patients (n=249) who met DSM-IV criteria for schizophrenia were randomly assigned to receive olanzapine monotherapy, risperidone monotherapy, divalproex plus olanzapine, or divalproex plus risperidone for 28 days. Divalproex was initiated at 15 mg/kg/day and titrated over 12 days to a maximum dosage of 30 mg/kg/day. Olanzapine and risperidone, were, respectively, initiated at 5 and 2 mg/day and were titrated over the first 6 days to respective target fixed daily dosages of 15 and 6 mg/day. Improvements from baseline were observed at all evaluation points throughout the 28-day treatment period in the two combination therapy and the two antipsychotic monotherapy groups, with statistically significant treatment differences favoring combination therapy as soon as day 3 for Positive and Negative Syndrome Scale (PANSS) total score, derived Brief Psychiatric Rating Scale (BPRSd) total score, as well as PANSS and BPRSd subscales. These findings were confirmed in post hoc repeated-measures analyses of variance in which treatment differences favoring combination therapy were observed for PANSS total (p=0.020) and PANSS positive scale scores (p=0.002). Both combination therapy and antipsychotic monotherapy were well tolerated. Treatment with divalproex in combination with an atypical antipsychotic agent resulted in earlier improvements in a range of psychotic symptoms among acutely hospitalized patients with schizophrenia. Further evaluation is warranted to confirm these findings.