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

National Taiwan University

Status and phase

Completed

Phase 4

Conditions

Schizoaffective Disorder

DSM-IV Schizophrenia

Treatments

Drug: Aripiprazole

Study type

Interventional

Funder types

Other

Identifiers

NCT00545467

200705030M

Details and patient eligibility

About

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.

Full 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:

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.

Enrollment

79 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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