Risperidone alone versus risperidone plus valproate in the treatment of patients with schizophrenia and hostility

Int Clin Psychopharmacol. 2007 Nov;22(6):356-62. doi: 10.1097/YIC.0b013e3281c61baf.


The objective of the study was to compare the antiaggressive efficacy of risperidone monotherapy versus risperidone plus valproate in patients with schizophrenia. This was an 8-week open-label randomized parallel group clinical trial in hospitalized adults diagnosed with schizophrenia and with hostile behavior. Patients were randomly assigned to receive risperidone alone (n=16) or risperidone plus valproate (n=17). To minimize bias, raters were blinded to the assigned treatment arm. Outcome measures included the Positive and Negative Syndrome Scale (PANSS), Buss-Durkee Hostility Inventory (BDHI), Barratt Impulsiveness Scale (BIS), Nurses Observation Scale for Inpatient Evaluation (NOSIE), and the Overt Aggression Scale (OAS). Although significantly fewer patients randomized to monotherapy completed the study (chi(2)=8.62, d.f.=1, P=0.003), no significant differences between monotherapy or combination treatment were observed in change of the BDHI, BIS, NOSIE, PANSS total scores, OAS measures of aggressive behavior or the hostility item of the PANSS. In conclusion, although patients receiving combination treatment were more likely to complete the study, we were unable to detect a meaningful advantage for combination therapy as measured by rating scales.

Trial registration: ClinicalTrials.gov NCT00308360.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aggression / drug effects
  • Aggression / psychology
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use
  • Diarrhea / chemically induced
  • Drug Therapy, Combination
  • Female
  • Hostility*
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Psychiatric Status Rating Scales
  • Risperidone / adverse effects
  • Risperidone / therapeutic use*
  • Schizophrenia / diagnosis
  • Schizophrenia / drug therapy*
  • Tablets, Enteric-Coated
  • Treatment Outcome
  • Valproic Acid / adverse effects
  • Valproic Acid / therapeutic use*
  • Vomiting / chemically induced


  • Anticonvulsants
  • Antipsychotic Agents
  • Tablets, Enteric-Coated
  • Valproic Acid
  • Risperidone

Associated data

  • ClinicalTrials.gov/NCT00308360