A Study of the Effectiveness and Safety of Risperidone as add-on Therapy to Mood Stabilizers in the Treatment of Manic Episodes Associated With Bipolar Disorder
Condition: Bipolar Disorders; 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 additional therapeutic agents in the treatment
      of patients who are not responsive to mood stabilizers alone. This is a randomized,
      double-blind, placebo-controlled 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. Treatment of one group of patients with haloperidol
      is used as an internal control in the trial. The study has two phases: a double-blind
      treatment phase (3 weeks) and an open-label phase (10 weeks). During the double-blind
      treatment phase patients receive risperidone, haloperidol, or placebo tablets to be taken
      once a day at gradually increasing doses (adjusted to 1 to 6 mg/day for risperidone and 2 to
      12 mg/day for haloperidol), while continuing treatment with a mood stabilizer (lithium or
      valproate). In the open-label phase all patients receive risperidone with the dosage
      gradually adjusted to achieve optimal effectiveness (dose range of 0 to 6 mg/day); in this
      phase patients continue therapy with a mood stabilizer (lithium, valproate, or, for this
      phase only, carbamazepine). The primary measure of effectiveness is the change in the Young
      Mania Rating Scale (YMRS) total score from baseline to end of double-blind treatment.
      Additional assessments of effectiveness 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 double-blind
      treatment, and at the end of study. The study hypothesis is that daily treatment with
      risperidone as add-on therapy provides better effectiveness than placebo, as measured by
      Young Mania Rating Scale scores, in the treatment of the manic phase of bipolar disorder.
      Double-blind (daily doses, taken orally once a day) - Days 1 and 2: risperidone 2 mg,
      haloperidol 4 mg, or placebo. Days 3 and 4: risperidone 1 - 4 mg, haloperidol 2 - 8 mg, or
      placebo. Days 5 - 21: risperidone 1 - 6 mg, haloperidol 2 - 21 mg, or placebo. Open-label:
      risperidone 0 - 6 mg/day for 10 weeks.
    

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