Effect of Divalproex Combined with Olanzapine or Risperidone in Patients with an Acute Exacerbation of Schizophrenia

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.

Selective epigenetic alteration of layer I GABAergic neurons isolated from prefrontal cortex of schizophrenia patients using laser-assisted microdissection

“…The long-used drug valproate has recently been shown to be active in the brain as an HDAC inhibitor 62 and has been shown to be beneficial in the treatment of SZP when coadministered with neuroleptic medications. 68,69 HDACs exist in many distinct isoforms showing tissue-specific expression patterns. Administration of elevated doses of valproate to SZP inhibits multiple HDAC isoforms, increasing with similar efficacy the acetylated histone content of many different brain regions.…”

Efeitos adversos metabólicos de antipsicóticos e estabilizadores de humor

“…al. 59 analyzed a clinical trial to assess efficacy of the association between divalproex and treatment with risperidone or olanzapine in acute schizophrenia and found a protective effect on increased total cholesterol in groups that used combined therapy. However, on the contrary, Isojärvi et al 20 found high triglyceride levels and low HDL levels in women with epilepsy taking valproic acid, compared with controls.…”

Valproic Acid Induces Manifestations of Simultaneous Dopamine Enhancement and Reduction in Schizophrenia

“…Our article discussing valproic acid (VPA) augmentation of atypical antipsychotics in schizophrenia (Casey et al, 2003) re-stated our position that pharmacological doses of VPA affect GABA, and subsequently dopamine (Wassef et al, 1999. Dr Winterer's letter (Winterer, 2003) disagreed.…”