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Amisulpride
See also Neuroleptic drugs
General information
Amisulpride is an atypical antipsychotic drug, a benzamide derivative, which may have a low propensity to cause extrapyramidal symptoms [ ].
Amisulpride 600–1200 mg/day for 3 months was effective and well tolerated in 445 patients with schizophrenia aged 18–45 years [ ]. During this time, 124 patients (28%) dropped out of the study; 21% reported adverse events, neurological (35%), psychiatric (15%), or endocrine (9.1%). Seven adverse events were assessed as serious: two suicides, two suicide attempts, one neuroleptic malignant syndrome, one somnolence, and one worsening of arteritis.
A lower dose of amisulpride (50 mg) has been tested in 20 healthy elderly volunteers (aged 65–79 years) [ ]. There were no serious adverse events, but one subject reported a moderate headache for 18 hours, a second subject vomited 9 hours after dosing, and a further subject complained of mild somnolence for 12 hours starting 4 hours after dosing; however, there were no extrapyramidal symptoms, clinically significant hemodynamic variations, or electrocardiographic abnormalities.
Drug studies
Observational studies
The prescribing of amisulpride for 811 schizophrenic in-patients from 240 psychiatric hospitals was monitored for 8 weeks; prescribed dosages were in the lower range of what is recommended for acute cases: the mean dose on day 56 was on average 550 mg/day, range 100–1600 mg/day [ ]. For the most severe cases there was a tendency for higher doses to be related to better improvement in positive symptoms and in negative symptoms; this correlation was not found in the least severe cases. The authors pointed out that this supports the notion that in more severe cases higher doses should be prescribed, while in milder cases lower doses may be sufficient; this would be in line with existing prescribing recommendations (800 mg/day as a standard dose in severe and recurrent episodes and especially in hospital; in the case of an insufficient response, the dose can be increased to 1200 mg/day) [ ].
Comparative studies
Similarly to other antipsychotic drugs, amisulpride has been used in psychiatric diseases other than schizophrenia. Amisulpride 50 mg/day (n = 94, mean age 50 years, 33% men) and acetyl- l -carnitine 1000 mg/day (n = 99, mean age 45 years, 30% men) have been compared in a 12-week double-blind study in 193 patients with pure dysthymia [ ]. There was improvement in both treatment groups throughout the study with no statistically significant differences. There were 21 dropouts related to adverse events in patients taking amisulpride and three in patients taking acetyl- l -carnitine; 15 patients had increased prolactin concentrations; four events (three in patients taking amisulpride and 1 in a patient taking acetyl- l -carnitine) were judged severe.
Comparisons with placebo and other antipsychotic drugs
In a randomized double-blind study, there were no differences in the numbers of patients with at least one adverse effect with amisulpride 100 mg (24%; n = 18), amisulpride 50 mg (25%; n = 21), or placebo (33%; n = 27) [ ]. Few patients had endocrine symptoms (2 out of 160 in the amisulpride groups).
Two narrative reviews of amisulpride have been published [ , ]. The authors emphasized that amisulpride in low dosages (below 300 mg/day) causes a similar incidence of adverse effects to placebo; nevertheless, at higher dosages (400–1200 mg/day), the overall incidence of adverse events in those taking amisulpride was similar to that in patients taking haloperidol, flupenthixol, or risperidone. The most commonly reported adverse events associated with higher dosages of amisulpride were extrapyramidal symptoms, insomnia, hyperkinesia, anxiety, increased body weight, and agitation. The incidence of extrapyramidal symptoms was dose-related. In elderly people, amisulpride can cause hypotension and sedation. There are no systematic published data on efficacy in children aged under 15 years.
In an extensive review of 19 randomized studies for the Cochrane Library (n = 2443), most of the trials were small and of short duration [ ]. The data from four trials with 514 participants with predominantly negative symptoms suggested that low-dose amisulpride (up to 300 mg/day) was more acceptable than placebo (n = 514; RR = 0.6; 95% CI = 0.5, 0.8).
A meta-analysis of 10 randomized controlled clinical trials of amisulpride in “acutely ill patients” (n = 1654) has been published, supported in part by a grant from Sanofi–Synthélabo, the marketing authorization holder [ ]. Amisulpride was significantly better than conventional antipsychotic drugs by about 11 percentage points on the Brief Psychiatric Rating Scale. In four studies in patients with “persistent negative symptoms,” amisulpride was significantly better than placebo (n = 514), but there was no significant difference between amisulpride and conventional drugs (only three trials; n = 130). Low doses of amisulpride (50–300 mg/day) were not associated with significantly more use of antiparkinsonian drugs than placebo (n = 507), and usual doses caused fewer extrapyramidal adverse effects than conventional antipsychotic drugs (n = 1599). In studies in acutely ill patients, significantly fewer patients taking amisulpride dropped out compared with patients taking conventional drugs, mainly owing to fewer adverse events; there were no significant differences in dropout rates between amisulpride and conventional antipsychotic drugs (three small studies).
Eighteen randomized controlled trials that compared amisulpride with conventional neuroleptic drugs or placebo in patients with schizophrenia have been combined in a meta-analysis [ ]. The differences in the mean effect size for efficacy clearly showed that all types of neuroleptic drugs were more effective than placebo, but the difference in mean effect size for all neuroleptic drugs versus placebo (n = 2000) was only 25%. Amisulpride was associated with fewer extrapyramidal adverse effects and fewer drop-outs because of adverse events than conventional neuroleptic drugs. More risperidone recipients than amisulpride recipients had endocrine problems, but the difference was not statistically significant. Clozapine and olanzapine had the greatest potential to cause weight gain; after 10 weeks of treatment, mean increases in weight were 4.4 kg with clozapine and 4.1 kg with olanzapine. Risperidone also caused weight gain (a mean increase of 2.1 kg after 10 weeks), while ziprasidone caused the least gain; amisulpride has since been found to cause minor weight gain, about 0.8 kg after 10 weeks.
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