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

Phase 4

Completed

• Conditions: Schizoaffective Disorder; DSM-IV Schizophrenia
• Interventions: Drug: Aripiprazole

• Registration Number: NCT00545467
• Lead Sponsor: National Taiwan University Hospital

Brief Summary

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

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:

1. Fast tapering of the previous medication within 1 week after initiating aripiprazole for 2 weeks.

2. 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:

1. 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.

2. Elucidate both pharmacokinetic and pharmacodynamic factors associated with clinical efficacy of aripiprazole.

Study Timeline

• Study Start: 2007-08
• Study First Submitted: 2007-10-15
• Study First Submitted QC: 2007-10-15
• Study First Posted: 2007-10-17
• Primary Completion: 2009-06
• Study Completion: 2009-07
• Status Verified: 2012-01
• Last Update Submitted: 2012-05-16
• Last Update Posted: 2012-05-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 79

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Aripiprazole	fast tapering of the previous medication within 1 week after initiating aripiprazole for 2 weeks
2	Aripiprazole	slow tapering of the previous medication within 4 weeks after initiating aripiprazole for 2 weeks

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
HPLC analysis Genotyping	on days 0, 14, 56

Trial Locations

Locations (1)

Department of Psychiatry, National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan