Risperdal Consta for Bipolar Disorder

Study Overview
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Brief Summary
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We recruited 50 consenting adult subjects with DSM-IV TR diagnoses of bipolar disorder who were about to initiate or switch their current antipsychotic agent. Only 48 patients (23 in the risperidone LAI group and 25 in the oral AAP group) contributed data to the assessments. Patients were titrated and cross-tapered during a 3 month titration and stabilization phase. They were followed for an additional 12 months. Clinical outcomes such as study drop out, adverse events, worsening of symptoms, crisis interventions, need for additional medication, hospitalizations etc. were evaluated from months 3 to 15. The numbers of clinical events (pooled) will be used to evaluate if the long acting injectable form of risperidone has an advantage over the oral second generation antipsychotic agents in terms of treatment continuity and clinical stability.

Detailed Description
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OBJECTIVE: To evaluate if a long acting injectable form of risperidone offers clinical advantages over comparison oral second generation antipsychotic agents following titration and stabilization in bipolar subjects. In keeping with current practice, it is expected the vast majority of patients will also be receiving either lithium or valproate or other anticonvulsants. Following the stabilization phase several clinical events will be evaluated for up to 15 months in the two treatment groups to examine differences in clinical outcomes between those receiving the injectable versus oral medicines. RESEARCH PLAN: We intend to recruit 50 consenting adult subjects with DSM-IV TR diagnoses of bipolar disorder who are about to initiate or to switch their antipsychotic agent. Patients will be titrated and cross-tapered during a 3 month titration and stabilization phase. Those who transition successfully and show some improvement will be followed for an additional 12 months. Clinical outcomes such as study drop out, adverse events, worsening of symptoms, crisis interventions, need for additional medication, hospitalizations etc. will be evaluated from months 3 to 15. The numbers of clinical events (pooled) will be used to evaluate if the long acting injectable form of risperidone has an advantage over the oral second generation antipsychotic agents in terms of treatment continuity and clinical stability. METHODS: An open design, but treatment to either the long acting risperidone or to the oral second generation antipsychotic agents is randomly assigned. A board independent of the day-to-day clinical events will code the primary clinical outcomes of interest without knowledge of treatment assignment. The board will be provided clinical summaries of these events without revealing the treatment assignment. SIGNIFICANCE: The use of a long acting injectable second generation antipsychotic agent may offer advantages of treatment continuity and adherence in bipolar patients permitting improved clinical stability and improved psychosocial and functional outcomes. Such stability is difficult to achieve in the face of frequent treatment discontinuations seen with oral agents. The improved tolerability of the second generation antipsychotic agents may change the perception of long acting injections. For instance, these agents are likely to be more acceptable to patients, families and clinicians and therefore likely be used much sooner in the treatment algorithms of bipolar patients than in the past. This study will provide a treatment effect size to statistically power future comparisons of long-acting injectable vs. oral antipsychotic agents in persons with bipolar disorder

Official Title
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A Random Assignment,Parallel Group, Open Label Comparison of Clinical Outcomes and Resource Utilization Among Bipolar Disorder Patients Receiving Either Long Acting Injectable Risperidone Microspheres (Risperdal Consta® ) or Other Second Generation Oral Antipsychotic Agents: A 15 Month Study

Conditions
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Bipolar I Disorder

Intervention / Treatment
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* Drug: Injectable Risperidone (Consta) or oral antipsychotic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DSM-IV - TR diagnoses of bipolar disorder (I or II or NOS). Age 18 to 70 years Men or women Any Ethnicity Currently receiving or willing to receive treatment at sites associated with the Western Psychiatric Institute and Clinic -University of Pittsburgh Medical Center (inpatient or ambulatory) or Mon Yough Community Services, Inc. or at Mayview State Hospital, Bridgeville, PA (inpatient) Able to provide competent and sign an informed consent document It is clinically appropriate in the eligible individual to consider antipsychotic treatment for at least 15 months (clinician and investigator determined) It is clinically appropriate to switch antipsychotic treatment to one of the second generation antipsychotic agents being evaluated in this study. There is no known contraindication for the use of either risperidone or for more than two of the antipsychotic agents being considered in the study (Investigator determined) At entry (at the screening visit, and just prior to randomization) Y-MRS (Young-Mania rating scale, Young et al., 1978) total score > 15 in bipolar disorder patients entering in a manic or mixed or hypomanic or NOS episode. Either life-time or current comorbid substance abuse or dependence is permitted (unless the Investigator and referring physician opines the substance abuse is likely to significantly interfere with either the diagnosis of the Axis I condition or to compromise patients safety due to withdrawal issues (Investigator determined). Screening physical and laboratory/EKG procedures are within acceptable limits Exclusion Criteria: Actively suicidal or dangerous to others (Investigator opines that it is inappropriate to involve the potential subject in the study) Pregnant or lactating women Women in the reproductive age group who are not using any acceptable contraception (abstinence is not acceptable) or intend to become pregnant during the trial Subjects who are likely to face incarceration during the study duration (and for those already in the study, the continued participation of such subjects will be evaluated on a case-by-case basis) Patients currently receiving clozapine (or within six weeks prior to randomization) are ineligible for the study Subjects currently receiving a depot neuroleptic injectable agent, or within 2 injection cycles of receiving the injection prior to randomization. Allergy or serious side effects (for instance - neuroleptic malignant syndrome) to either risperidone or to more than two of the other second-generation antipsychotic agents that have been approved for use in the U.S.A. (olanzapine, quetiapine, ziprasidone, aripiprazole-per investigator and referring clinician). Treatment resistance to either risperidone, or to more than two of the other antipsychotic agents in this trial (olanzapine, quetiapine, ziprasidone, aripiprazole). This is the first episode of mania, mixed or hypomania for patients. Current (or within one month prior to randomization) participation in an investigational drug/device study. Currently participating in another study that would confound the present study objectives (per investigator)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Oral Risperidone followed by Long acting Risperidone injections (Consta) | Drug: Injectable Risperidone (Consta) or oral antipsychotic<br>* Injectable Risperidone (Consta) from 12.5 to 50 mg q 2 weeks Oral antipsychotic agents, olanzapine, quetiapine, ziprasidone, aripiprazole in doses approved in the US for bipolar disorder<br>* Other names: Olanzapine (Zyprexa), Quetiapine (Seroquel), Ziprasidone (Geodon), Aripiprazole (Ablify);|
| Active Comparator: 2<br>Oral second generation antipsychotic agents other than clozapine or risperidone (olanzapine, quetiapine, ziprasidone, aripiprazole) | Drug: Injectable Risperidone (Consta) or oral antipsychotic<br>* Injectable Risperidone (Consta) from 12.5 to 50 mg q 2 weeks Oral antipsychotic agents, olanzapine, quetiapine, ziprasidone, aripiprazole in doses approved in the US for bipolar disorder<br>* Other names: Olanzapine (Zyprexa), Quetiapine (Seroquel), Ziprasidone (Geodon), Aripiprazole (Ablify);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the Number of Clinical Events (Pooled) Occurring Between 3-15 Months Following a Switch/Stabilization of the Antipsychotic Agents Among Patients Who Receive Either Risperidal Consta or One of the 4 Marketed 2nd Generation Antipsychotic Agents. |  | Upto 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMI | BMI at baseline and at end of 15 months for Risperidone LAI and oral AAP groups | baseline to end of 15 months | 
| Number of Participants With Treatment - Emergent Hyperglycemia | Number of participants with hyperglycemia based on safety labs | from baseline to end of 15 months | 
| Number of Participants With Treatment Emergent Hyperlipidemia | Number of participants with Hyperlipidemia as determined by safety labs | from baseline to end of 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar I Disorder, Risperidone Consta - Long Acting Injection, Oral second generation antipsychotic agents