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.
Condition: Bipolar Disorder; Manic Disorder
MeSH terms: Mania; Bipolar Disorder
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): risperidone
Intervention type(s): Drug
Intervention MeSH terms: Risperidone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: risperidone; antipsychotic agents; bipolar disorders; manic episode