Evaluation of the Strategies of Switching Schizophrenia Patients to Aripiprazole From Other Antipsychotic Agents

Study Overview
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Brief Summary
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The purpose of this study is to determine whether moderately ill Asian schizophrenic patients can be switched from their previous antipsychotic medication to aripiprazole with minimal adverse clinical consequences, and elucidate both pharmacokinetic and pharmacodynamic factors associated with clinical efficacy of aripiprazole.

Detailed Description
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Aripiprazole (commercial name abilify) is the first commercially available drug with dopamine partial agonist effects approved for the treatment of schizophrenia and bipolar disorder since 2002 in the U.S. It reduces negative symptoms of schizophrenia efficiently and has a markedly lower incidence of extrapyramidal symptoms and tardive dyskinesia. However, the process of switching other antipsychotic agents to aripiprazole can result in a re-emergence or worsening of psychosis, along with unpleasant side effects such as insomnia, nausea, vomiting, anxiety and agitation. On the basis of a prior study demonstrating the efficacy and safety of aripiprazole in Taiwan population, we hence propose to apply a combined use of pharmacogenomics and therapeutic drug monitoring in the evaluation of the strategies of switching stable schizophrenia patients to aripiprazole from other antipsychotic agents. We will evaluate their cytochrome P450 background along with other potential candidate genes of schizophrenia. This 2-year proposal will examine the relative efficacy, safety and tolerability of two different strategies for switching stable inpatients/outpatients from prior antipsychotic monotherapy to aripiprazole 15 mg/day monotherapy using two different strategies: Fast tapering of the previous medication within 1 week after initiating aripiprazole for 2 weeks. Slow tapering of the previous medication within 4 weeks after initiating aripiprazole for 2 weeks. A total of 200 stable schizophrenia patients will be randomized with open label to two strategies. We expect to achieve the following results: Developing a protocol that has high probability of switching successfully schizophrenia patients to aripiprazole, which is effective in treatment refractory cases and has a markedly lower incidence of severe side effects, from other antipsychotics. Elucidate both pharmacokinetic and pharmacodynamic factors associated with clinical efficacy of aripiprazole.

Official Title
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Evaluation of the Strategies of Switching Schizophrenia Patients to Aripiprazole From Other Antipsychotic Agents: Combination of Pharmacogenomics and Therapeutic Drug Monitoring

Conditions
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DSM-IV Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Drug: Aripiprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and non-lactating, non-pregnant women who are aged 18 to 65 years primary diagnosis of DSM-IV schizophrenia or schizoaffective disorder taking a stabilized dose of a single oral antipsychotic for at least 1 month prior to study entry cannot have been hospitalized for an exacerbation of schizophrenia or schizoaffective disorder for at least 2 months Exclusion Criteria: having other psychiatric disorders hospitalizing for acute exacerbation of patients' condition within 2 months having taken a selective serotonin reuptake inhibitor (SSRI) within 4 weeks of screening a first episode of schizophrenia or schizoaffective disorder a clinically significant neurological abnormality other than tardive dyskinesia or EPS current diagnosis of psychoactive substance dependence or a historical drug or alcohol abuse within 1 month before the beginning of the study treatment with an investigational drug within 4 weeks prior to randomization requiring to take medication that inhibits the microsomal enzyme CYP2D6 or inhibits or acts as a substrate for CYP3A4

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>fast tapering of the previous medication within 1 week after initiating aripiprazole for 2 weeks | Drug: Aripiprazole<br>* Aripiprazole will be given as a fixed does, 15 mg/day, orally throughout 8 weeks in the 2 arms.<br>* Other names: abilify;|
| Active Comparator: 2<br>slow tapering of the previous medication within 4 weeks after initiating aripiprazole for 2 weeks | Drug: Aripiprazole<br>* Aripiprazole will be given as a fixed does, 15 mg/day, orally throughout 8 weeks in the 2 arms.<br>* Other names: abilify;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment efficacy was assessed using PNASS, Clinical Global Impression (CGI) Scale, and EPS rating scales |  | on days 0, 7, 14, 28, 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HPLC analysis Genotyping |  | on days 0, 14, 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aripiprazole, schizophrenia, antipsychotics, pharmacogenomics, cytochrome P450 enzyme