A Randomized, Double-blind, Comparison of the Efficacy and Safety of Amisulpride Versus Low-dose Amisulpride Plus Low-dose Sulpiride in the Treatment of Schizophrenia

Study Overview
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Brief Summary
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Background: Surveys have shown that antipsychotic drug combinations are frequently prescribed. Amisulpride, an atypical antipsychotic agent, has low incidence of extrapyramidal symptom (EPS) but with high cost compared to sulpiride. The objective of the study is to compare the efficacy and safety of the 800-mg/d amisulpride and 400-mg/d amisulpride plus 800-mg sulpiride in the treatment of acute psychotic exacerbations of schizophrenia. Method: In this 6-week, double-blind, fixed-dose study, patients with schizophrenia are randomly assigned to amisulpride (800 mg/d) or amisulpride (400 mg/d) plus sulpiride (800 mg/d).The hypothesis is that the two treatment groups have the similar efficacy and safety, but different cost.

Detailed Description
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Background: Antipsychotic monotherapy is recognized as the treatment of choice for patients with schizophrenia. Surveys have shown that antipsychotic drug combinations are frequently prescribed, yet few clinical studies have examined this practice. Amisulpride, an atypical antipsychotic agent, has low incidence of extrapyramidal symptom (EPS) but with high cost compared to sulpiride. It has been reported that mean doses of low-potency typical antipsychotics less than 600 mg/day of chlorpromazine equivalent dose has no higher risk of EPS than atypical antipsychotics. The objective of the study is to compare the efficacy and safety of the 800-mg/d amisulpride and 400-mg/d amisulpride plus 800-mg sulpiride in the treatment of acute psychotic exacerbations of schizophrenia. Method: In this 6-week, double-blind, fixed-dose study, patients with schizophrenia (DSM-IV diagnosis) are randomly assigned to amisulpride (800 mg/d) or amisulpride (400 mg/d) plus sulpiride (800 mg/d). The hypothesis is that the two treatment groups have the similar efficacy and safety, but different cost. The efficacy assessment was the change from baseline in the score on the Clinical Global Impression-Severity (CGI-S), Positive and Negative Syndrome Scale (PANSS) and subscales (positive scale, negative scale, general psychopathology scale), Calgary Depression Scale for Schizophrenia (CDSS), and Global Assessment of Functioning (GAF). Safety assessments include the change from baseline on Simpson-Angus Rating Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Scale (BAS), and UKU Side-effects Rating Scale (UKU), and the change from baseline in prolactin levels, body weight, vital sign, blood pressure, AC glucose level, and lipid profiles(cholesterol, high density lipid protein [HDL], low density lipid protein [LDL], and triglyceride [TG]).

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: full-dose amisulpride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: schizophrenia CGI >=4 washout of antipsychotics at least 3-5 days written informed consents Exclusion Criteria: History of serious adverse events to sulpiride or amisulpride History of neuroleptic malignant syndrome or tardive dyskinesia to antipsychotics treatment-resistant schizophrenia long-acting antipsychotics in the past 3 months comorbid with substance abuse/dependence female subjects with pregnancy severe physical illness

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sulpiride plus amisulpride<br>sulpiride 800mg/d + amisulpride 400mg/d | Drug: full-dose amisulpride<br>* amisulpride 800mg/d<br>* Other names: Solian;|
| Active Comparator: full-dose amisulpride<br>amisulpride 800mg/d | Drug: full-dose amisulpride<br>* amisulpride 800mg/d<br>* Other names: Solian;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline in Positive and Negative Syndrome Scale (PANSS) total scores |  | The PANSS was rated at baseline, and again at weeks 1, 2, 3, 4, and 6 (or on early termination). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes from baseline in the scores on several psychopathology scales for efficacy | psychopathology scales for efficacy include: Clinical Global Impression-Severity (CGI-S), PANSS positive scale, PANSS negative scale, PANSS general psychopathology scale, Calgary Depression Scale for Schizophrenia (CDSS), and Global Assessment of Functioning (GAF) | The CGI-S, PANSS, CDSS, and GAF were rated at baseline, and again at weeks 1, 2, 3, 4, and 6 (or on early termination). | 
| Assessments of safety for extrapyramidal symptoms (EPS) | The severity of EPS was assessed by the following neurological scales: the Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Scale (BAS), and the Simpson-Angus Rating Scale (SAS) | AIMS, BAS, and SAS were administered at baseline and at weeks 1, 2, 3, 4, and 6 (or on early termination) | 
| Assessments of safety for general adverse events | General adverse events were evaluated by a standardized the UKU Side Effect Rating Scale. A score of 1, 2 or 3 on any UKU item that first occurred or worsened during treatment indicated adverse events cases. | UKU was administered at baseline and at weeks 1, 2, 3, 4, and 6 (or on early termination) | 
| Other safety of clinical trial | Body weights, body mass index (BMI), pulse rate, blood pressure (systolic and diastolic), 12-lead electrocardiogram (ECG) for QTc intervals (Bazett's correction of QT interval), and laboratory tests were performed to determine safety. Laboratory tests included fasting glucose, liver function (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), renal function (blood urea nitrogen [BUN], creatinine), lipid profiles (triglycerides, cholesterol, high density lipoprotein [HDL], and low density lipoprotein [LDL]), and prolactin level. | Body weight, BMI, pulse rate, and blood pressure were checked at baseline and at weeks 1, 2, 3, 4, and 6 (or on early termination). ECG and laboratory tests were assessed at baseline and week 6. | 
| Assessments of quality of life | The SF-36, with two primary-factor analytic components: the physical component summary and the mental component summary, was used to measure quality of life. | Medical Outcomes Study Short-Form 36 was assessed at baseline and week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizophrenia, amisulpride, sulpiride, antipsychotic combination