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

This study has been completed.
Sponsor:
Information provided by:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00253149
First received: November 10, 2005
Last updated: January 20, 2011
Last verified: January 2011
  Purpose

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.


Condition Intervention Phase
Bipolar Disorders
Manic Disorder
Drug: risperidone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: The Safety And Efficacy Of Risperdal� (Risperidone) Versus Placebo Versus Haloperidol As Add-On Therapy To Mood Stabilizers In The Treatment Of The Manic Phase Of Bipolar Disorder

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • Change in Young Mania Rating Scale (YMRS) total score from baseline to end of double-blind treatment

Secondary Outcome Measures:
  • 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.

Enrollment: 158
Study Completion Date: April 1999
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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Bipolar Disorder according to Diagnostic and Statistical Manual of Mental Diseases, 4th edition (DSM-IV)
  • hospitalized for mania with a score >=20 on the Young Mania Rating Scale (YMRS) (patients with concurrent symptoms of depression are eligible)
  • inpatient for a minimum of the first 4 days of double-blind treatment
  • therapy with lithium or valproate (mood stabilizers) at start of treatment with study medication
  • 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 4 weeks of starting the study
  • seizure disorder requiring medication
  • known sensitivity to risperidone, haloperidol, lithium, valproate or carbamazepine
  • pregnant or nursing females, or those lacking adequate contraception.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00253149

Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00253149     History of Changes
Other Study ID Numbers: CR006040
Study First Received: November 10, 2005
Last Updated: January 20, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
risperidone
antipsychotic agents
bipolar disorders
manic episode

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Antipsychotic Agents
Risperidone
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on July 22, 2014