• 作者：Aless ; ro Musenga ; Roberto M ; rioli ; Emanuele Morganti ; Salvatore Fanali ; Maria Augusta Raggi
• 关键词：Amisulpride ; Enantiomers ; Capillary electrophoresis ; Chiral separation ; Cyclodextrin ; Quality control
• 刊名：Journal of Pharmaceutical and Biomedical Analysis
• 出版年：2008
• 期刊代码：65_07317085
• 类别：ch
• 出版时间：14 April 2008
• 卷：46
• 期：5
• 页码：966-970
• 文件大小：201 K

The safety profile of AMI based on the results of 5 short-term and 4 long-term studies will be presented. Overall, 1170 patients were evaluated 749 of whom were treated with AMI, 240 with haloperidol (H), 62 with flupentixol and 119 received placebo. 838 (72%) patients were included in studies in productive schizophrenia and 332 (28%) patients in studies in deficit schizophrenia. 104 patients received AMI for at least 11 months. Clinical safety data were collected by either spontaneous reporting and/or adverse event scales.

Adverse reactions associated to antipsychotics may be classified in two categories:

1. Some are frequent and not related to an individual hypersensitivity:

- Psychic disorders: usually mild and well tolerated.

- Increased hyperprolactinaemia: with clinical consequences particularly in women. Informing patients on their occurrence and reversibility make them usually acceptable.

- Early extrapyramidal symptoms: they are improved by antiparkinsonian drugs, and reversible with discontinuation of antipsychotics. However their incidence (> 50%with some antipsychotics), the functional and psychological consequences make them a crucial argument for choice between antipsychotics. Decrease of their incidence is one of the criteria of identification of “atypical antipsychotics”.

2. Uncommon reactions usually more severe: seizures, in at-risk patients; tardive dyskinesia, malignant syndrome, immediately life-threatening; sudden death and/or life-threatening cardiac disorders; less specific: agranulocytosis and liver disorders.

In summary, safety evaluation of an antipsychotic is based on the incidence of early extrapyramidal symptoms and on the occurrence of the serious or fatal reactions.

Based on the above-mentioned studies, the safety profile of amisulpride may be summarized as follows:

1. Incidence of early extrapyramidal syndromes:

In productive schizophrenia, they are less frequent with AMI (39%) at doses up to 800 mg/d than with H (58%) (UKU scale). In schizophrenia with negative symptoms, difference is much more important: 12%for AMI at doses up to 300 mg/d vs 52%for H (open report), and amisulpride is as well tolerated as placebo except for hyperprolactinaemia (6.6%).

2. Occurrence of serious or fatal/life-threatening reactions:

Seizures were not more frequent with amisulpride (2/749) than with placebo (3/119). Incidence of tardive dyskinesia with amisulpride was 4/749. No case of malignant syndrome, sudden death, cardiac disorders, agranulocytosis or hepatitis was recorded during the studies.

The clinical data from studies show that amisulpride can be safely used in schizophrenic patients with predominant positive symptoms as well as in schizophrenic patients with deficit symptoms.