Risperidone Alone Vs. Risperidone Plus Valproate in the Treatment of Patients With Schizophrenia and Hostility

This is an eight-week open-label randomized parallel group clinical trial focusing on the comparison of risperidone alone with risperidone plus valproate among hospitalized adult patients diagnosed with schizophrenia who also exhibit problems with hostility. Patients may have already been receiving risperidone or valproate (but not both) at study entry. Patients not receiving valproate at study entry were randomized to receive either risperidone alone or risperidone with valproate. For patients already receiving valproate at study entry, their antipsychotic medication(s) was switched to risperidone, and they were followed for a four-week lead-in period prior to baseline assessment and randomization to receive risperidone alone or continue with risperidone and valproate. We hypothesized that risperidone alone has an antiaggressive/antihostility effect, and that this effect is augmented by the co-administration of valproate.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Risperidone, divalproex

Detailed Description

Background: Patients with schizophrenia who also exhibit hostile behavior pose a formidable challenge for clinicians. Hostile behavior is a frequent reason for psychiatric admission, and is an obstacle for the successful reintegration of patients back into the community. Current treatment approaches have generally not been assessed under controlled conditions.

Method: This is an eight-week open-label randomized parallel group clinical trial focusing on the comparison of risperidone alone with risperidone plus valproate among hospitalized adult patients diagnosed with schizophrenia who also exhibit problems with hostility. Patients may have already been receiving risperidone or valproate (but not both) at study entry. Patients not receiving valproate at study entry were randomized to receive either risperidone alone or risperidone with valproate. For patients already receiving valproate at study entry, their antipsychotic medication(s) was switched to risperidone, and they were followed for a four-week lead-in period prior to baseline assessment and randomization to receive risperidone alone or continue with risperidone and valproate. Blinded raters completed a battery of assessments, including the Positive and Negative Syndrome Scale, Buss-Durkee Hostility Inventory, Barratt Impulsiveness Scale, and the Overt Aggression Scale. We hypothesized that risperidone alone has an antiaggressive/antihostility effect, and that this effect is augmented by the co-administration of valproate.

• Study Type: Interventional
• Enrollment: 46
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Orangeburg, New York, United States, 10962
      • Nathan S Kline Institute for Psychiatric Research and Rockland Psychiatric Center, Clinical Research and Evaluation Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1) Male or female, age 18 to 65 inclusive, diagnosed with schizophrenia (not including schizoaffective disorder) according to DSM-IV criteria using the Structured Clinical Interview for DSM-IV Axis I Disorders; 2) Referral from the treating psychiatrist/treatment team because of difficulties with poor impulse control; 3) At study entry the subject must have scored at least "3" ("mild" or above) on at least one of the following Positive and Negative Syndrome Scale items that comprise the activation factor: Hostility, Impulsivity, Excitement, or Uncooperativeness; 4) Capacity and willingness to give informed consent; 5) Adequate knowledge of English; 6) Absence of serious medical illness; and 7) Accessible, adequate veins likely to permit repeated venipunctures without major problems.

Exclusion Criteria:

1) Receiving both adequate amounts of valproate and risperidone at the time the inclusion criteria have been met. This was defined as a dose of valproate that was equal to or exceeding 1000 mg/day (or a plasma level equal to or greater than 50 micrograms/mL) for at least 2 weeks, and any dose of risperidone; 2) History of severe adverse reaction to either risperidone or valproate; 3) Administration of a slow-release antipsychotic (depot) within 30 days preceding randomization; and 4) Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Buss-Durkee Hostility Inventory
Barratt Impulsiveness Scale

Secondary Outcome Measures

Outcome Measure
Positive and Negative Syndrome Scale
Overt Aggression Scale

Collaborators and Investigators

• Sponsor: Nathan Kline Institute for Psychiatric Research
• Collaborators: Research Foundation for Mental Hygiene, Inc.; Janssen, LP
• Investigators: Principal Investigator: Leslie L Citrome, MD, MPH, Nathan S Kline Institute for Psychiatric Research and New York University School of Medicine; Principal Investigator: Jan Volavka, MD, PhD, Nathan S Kline Institute for Psychiatric Research and New York University School of Medicine

Publications and helpful links

General Publications

• Citrome L, Shope CB, Nolan KA, Czobor P, Volavka J. 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.

Helpful Links

• Nathan S Kline Institute for Psychiatric Research

Study record dates

Study Major Dates

• Study Start: September 1, 1999
• Study Completion: April 1, 2004

Study Registration Dates

• First Submitted: March 28, 2006
• First Submitted That Met QC Criteria: March 28, 2006
• First Posted (ESTIMATE): March 29, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): March 29, 2006
• Last Update Submitted That Met QC Criteria: March 28, 2006
• Last Verified: March 1, 2006

More Information

Terms related to this study

• Keywords: Impulsivity; Aggression; Hostility
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; GABA Agents; Anticonvulsants; Antimanic Agents; Valproic Acid; Risperidone
• Other Study ID Numbers: RIS-189