A Study of the Effectiveness and Safety of Risperidone Versus Placebo as add-on Therapy to Mood Stabilizers, in the Treatment of Manic Episodes Associated With Bipolar Disorder.

Phase 3

Completed

• Conditions: Bipolar Disorder; Manic Disorder

• Registration Number: NCT00250367
• Lead Sponsor: Janssen Pharmaceutica N.V., Belgium

Brief Summary

The purpose of the study is to evaluate the effectiveness and safety of risperidone (an antipsychotic medication) versus placebo as add-on therapy to mood stabilizers, in the treatment of manic episodes associated with bipolar disorder.

Detailed Description

Risperidone, widely used in the treatment of schizophrenia, has been shown to be effective in the treatment of manic and mixed episodes associated with bipolar disorders. Antipsychotic drugs like risperidone have also been used as therapeutic agents in the treatment of patients who are not responsive to mood stabilizers alone. This is a randomized, double-blind study to evaluate the effectiveness and safety of risperidone compared with placebo, as an addition to mood stabilizing drugs, in the treatment of patients experiencing manic episodes associated with bipolar disorder. The study has two phases: a double-blind treatment phase (3 weeks) and an open-label phase (10 weeks). To participate in the study, patients must be in-patients for a minimum of the first 4 days of double-blind treatment. During the double-blind treatment phase, patients receive risperidone or placebo tablets to be taken once a day at gradually increasing doses at investigator's discretion, up to a maximum dose of 6 mg/day, while continuing their treatment with a mood stabilizer (lithium, valproate, or carbamazepine). In the open-label phase, therapy with a mood stabilizer continues, and all patients receive risperidone with dosage gradually adjusted to achieve optimal effectiveness. The primary measure of effectiveness is the change in Young Mania Rating Scale (YMRS) total score from baseline to end of double-blind treatment. Additional efficacy measures include the Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impression (CGI), (which evaluates the change in severity of the disorder), and the Hamilton Depression Rating Scale (HAMD). Safety assessments include the incidence of adverse events throughout the study; measurement of vital signs (pulse and blood pressure) and evaluation of the presence and severity of extrapyramidal symptoms by the Extrapyramidal Symptom Rating Scale (ESRS) at specified intervals; and clinical laboratory tests (hematology, biochemistry, urinalysis) before study initiation, at completion of the double-blind treatment, and at the end of the study. The study hypothesis is that daily treatment with risperidone as add-on therapy provides better effectiveness than the addition of placebo, as measured by Young Mania Rating Scale scores, in the treatment of the manic phase of bipolar disorder. Risperidone 1 mg tablets, taken orally, once daily; Doses of 2 mg on Days 1 and 2, up to 4 mg on Days 3 and 4, and up to 6 mg (maximum dose) on Days 5 through 21. Same dose maintained through the 10 week open-label phase. Gradual dose adjustments are allowed to achieve optimal effectiveness.

Study Timeline

• Study Start: 1997-10
• Study Completion: 1999-11
• Study First Submitted: 2005-11-04
• Study First Submitted QC: 2005-11-04
• Study First Posted: 2005-11-08
• Status Verified: 2010-11
• Last Update Submitted: 2010-11-24
• Last Update Posted: 2010-11-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 151

Inclusion Criteria

• Patients hospitalized for mania with a score >=20 on the Young Mania Rating Scale (YMRS). (Patients with symptoms of depression are eligible)
• diagnosis of Bipolar Disorder according to Diagnostic and Statistical Manual of Mental Diseases, 4th edition (DSM-IV)
• receiving treatment with a mood stabilizer for a minimum of 2 weeks prior to study initiation, or beginning therapy with a mood stabilizer prior to treatment with study medication
• patients medically stable on the basis of physical examination, medical history and electrocardiogram results.

Exclusion Criteria

• Other Axis I DSM-IV diagnosis (except nicotine or caffeine dependence)
• history of alcohol or drug abuse or dependence within 3 months of starting the study
• seizure disorder requiring medication
• known sensitivity to risperidone, lithium, valproate or carbamazepine
• pregnant or nursing females, or those lacking adequate contraception.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change in Young Mania Rating Scale (YMRS) total score from baseline to end of double-blind treatment

Secondary Outcome Measures

Name	Time	Method
Changes from baseline to end of double-blind treatment in Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI) - severity, and Hamilton Depression Rating Scale (HAMD); incidence of adverse events throughout study.