Aripiprazole Augmentation for Clozapine-Treated Patients With Refractory Schizophrenia

Seoul National University Hospital61 enrolled

Overview

The purpose of this study is to determine whether aripiprazole augmentation is safe and effective in the treatment of clozapine-treated patients with refractory schizophrenia.

Clozapine is renowned for its efficacy in treating schizophrenia refractory to typical or atypical antipsychotics. Though the effectiveness of clozapine has been established, a considerable number of patients with schizophrenia are partially responsive or unresponsive to clozapine. In addition, long-term use of clozapine is associated with the development of obsessive-compulsive symptoms and metabolic syndrome. In order to overcome these short-comings and to increase efficacy, aripiprazole augmentation was implemented. Quantitative electroencephalogram will be used to monitor the occurrence of abnormal findings and to analyze the changes in electroencephalographic pattern with linear and non-linear methodology. Comparisons: Design of double-blind randomized placebo controlled study of patients at Refractory Schizophrenia Clinique in Department of Neuropsychiatry at Seoul National University Hospital.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Schizophrenia

Interventions

aripiprazoleDRUG

aripiprazole augmentation of clozapine

placeboDRUG

placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female patients, 18-65 years of age. * Patients must have a diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). * Female patients of menarche must be using a medically accepted means of contraception (e.g. oral contraceptives, Depo-Provera, abstinence). * Each patient must provide written informed consent after full explanation of study protocol, and authorized legal guardian must understand the nature of the study and must also give assent to study participation. * Patients must have a baseline (day 0) BPRS score of at least 35 or over 2 of 5 SANS global rating item scores of at least 3. * Patients have been receiving clozapine treatment for more than 1 year and there has been no change in clozapine dosage for more than 3 months. * Patients must have a history of antipsychotic treatment with at least 2 different kinds prior to clozapine administration. * Subjects who are fluent in Korean. Exclusion Criteria: * DSM-IV substance (except nicotine or caffeine) dependence within the past 1 year. * Female patients who are either pregnant or lactating. * Mental retardation (IQ \< 70). * Neurological disorders including epilepsy, stroke, or severe head trauma. * Clinically significant laboratory abnormalities, on any of the following tests: CBC with differential, electrolytes, BUN, creatinine, hepatic transaminases, urinalysis and EKG. * Prior history of aripiprazole non-response or intolerance. * BPRS score of \< 35 and over 4 of 5 SANS global rating item scores of \< 3. * Participation in a clinical trial of another investigational drug within 3 months (90 days) prior to study entry. * Treatment with an injectable depot neuroleptic within less than three dosing interval between the last depot neuroleptic injections and baseline (day 0). * History of electroconvulsive therapy within the past 3 months. * Subjects who are not fluent in Korean.

Locations (1)

Seoul National University Hospital

Seoul, South Korea

Outcomes

Primary Outcomes

Brief Psychotic Rating Scale (BPRS): Measure of efficacy will be changes in BPRS total and subscale scores from baseline to 8th week endpoint. Follow-up evaluation will be made every 6th month till 1 year after 8th week end point.

Time frame: one year

Schedule for Assessment of Negative Symptoms (SANS): Measure of efficacy will be changes in SANS total and subscale scores from baseline to 8th week endpoint. Follow-up evaluation will be made at 6 month and 12 month after 8th week end point.

Time frame: one year

Serum Prolactin Level

Time frame: one year

Body Mass Index & Abdominal Circumference

Time frame: one year

Lipid Panel with LDL Cholesterol

Time frame: one year

FBS-PP & HbA1c

Time frame: one year

Secondary Outcomes

Clinical Global Impression-Severity & Improvement (CGI-S & CGI-I)

Time frame: one year

Montgomery-Asberg Depression Rating Scale (MADRS)

Time frame: one year

Yale-Brown Obsessive Compulsive Scale (YBOCS)

Time frame: one year

Subjective Well-being under Neuroleptics scale (SWN)

Time frame: one year

Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS)

Data from ClinicalTrials.gov

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