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

• changes from baseline in the scores on several psychopathology scales for efficacy [ Time Frame: 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). ] [ Designated as safety issue: No ]
  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)
• Assessments of safety for extrapyramidal symptoms (EPS) [ Time Frame: AIMS, BAS, and SAS were administered at baseline and at weeks 1, 2, 3, 4, and 6 (or on early termination) ] [ Designated as safety issue: Yes ]
  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)
• Assessments of safety for general adverse events [ Time Frame: UKU was administered at baseline and at weeks 1, 2, 3, 4, and 6 (or on early termination) ] [ Designated as safety issue: Yes ]
  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".
• Other safety of clinical trial [ Time Frame: 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. ] [ Designated as safety issue: Yes ]
  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.
• Assessments of quality of life [ Time Frame: Medical Outcomes Study Short-Form 36 was assessed at baseline and week 6 ] [ Designated as safety issue: No ]
  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.

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.

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]).

• Experimental: sulpiride plus amisulpride
  sulpiride 800mg/d + amisulpride 400mg/d
  Intervention: Drug: full-dose amisulpride
• Active Comparator: full-dose amisulpride
  amisulpride 800mg/d
  Intervention: Drug: full-dose amisulpride

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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