Clinical trial NCT01615185: 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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Schizophrenia
Keywords: schizophrenia
amisulpride
sulpiride
antipsychotic combination
Lead sponsor: Kaohsiung Kai-Suan Psychiatric Hospital
Sponsor class: OTHER_GOV
First posted: 2012-06-08
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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 \[TG\]).

Eligibility criteria: 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

Primary outcomes:
measure: change from baseline in Positive and Negative Syndrome Scale (PANSS) total scores
timeFrame: The PANSS was rated at baseline, and again at weeks 1, 2, 3, 4, and 6 (or on early termination).
Secondary outcomes:
measure: changes from baseline in the scores on several psychopathology scales for efficacy
timeFrame: 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).
measure: Assessments of safety for extrapyramidal symptoms (EPS)
timeFrame: AIMS, BAS, and SAS were administered at baseline and at weeks 1, 2, 3, 4, and 6 (or on early termination)
measure: Assessments of safety for general adverse events
timeFrame: UKU was administered at baseline and at weeks 1, 2, 3, 4, and 6 (or on early termination)
measure: Other safety of clinical trial
timeFrame: 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.
measure: Assessments of quality of life
timeFrame: Medical Outcomes Study Short-Form 36 was assessed at baseline and week 6
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Kai-Suan Psychiatric Hospital
Study officials:
affiliation: Kai-Suan Psychiatric Hospital
name: Ching-Hua Lin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Leucht S, Wahlbeck K, Hamann J, Kissling W. New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis. Lancet. 2003 May 10;361(9369):1581-9. doi: 10.1016/S0140-6736(03)13306-5.
citation: Kapur S, Seeman P. Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: A new hypothesis. Am J Psychiatry. 2001 Mar;158(3):360-9. doi: 10.1176/appi.ajp.158.3.360.
citation: McKeage K, Plosker GL. Amisulpride: a review of its use in the management of schizophrenia. CNS Drugs. 2004;18(13):933-56. doi: 10.2165/00023210-200418130-00007.
citation: Chakos MH, Glick ID, Miller AL, Hamner MB, Miller DD, Patel JK, Tapp A, Keefe RS, Rosenheck RA. Baseline use of concomitant psychotropic medications to treat schizophrenia in the CATIE trial. Psychiatr Serv. 2006 Aug;57(8):1094-101. doi: 10.1176/ps.2006.57.8.1094.
citation: Lin CH, Wang FC, Lin SC, Huang YH, Chen CC, Lane HY. Antipsychotic combination using low-dose antipsychotics is as efficacious and safe as, but cheaper, than optimal-dose monotherapy in the treatment of schizophrenia: a randomized, double-blind study. Int Clin Psychopharmacol. 2013 Sep;28(5):267-74. doi: 10.1097/YIC.0b013e3283633a83.