Practical Issues with Amisulpride in the Management of Patients with Schizophrenia

• Published in: Clinical drug investigation 2008-01, Vol.28 (8), p.465-477
• Main Authors: Pani, Luca, Villagrán, José M., Kontaxakis, Vassilis P., Alptekin, Köksal
• Format: Article
• Language: English
• Subjects: Antipsychotic Agents - pharmacology; Antipsychotic Agents - therapeutic use; Antipsychotic drugs; Comparative analysis; Dosage and administration; Drug Resistance; Drug therapy; Drug Therapy, Combination; Humans; Internal Medicine; Medicine; Medicine & Public Health; Pharmacology/Toxicology; Pharmacotherapy; Review Article; Schizophrenia; Schizophrenia - drug therapy; Schizophrenic Psychology; Sulpiride - analogs & derivatives; Sulpiride - pharmacology; Sulpiride - therapeutic use
• ISSN: 1173-2563; 1179-1918
• DOI: 10.2165/00044011-200828080-00001

Amisulpride is an atypical antipsychotic with a significantly greater effect size than first-generation, typical antipsychotics, and efficacy at least similar to that of olanzapine and risperidone in large-scale clinical trials in schizophrenia. Amisulpride provides greater improvement in positive and negative symptoms of schizophrenia, a better long-term outcome than typical antipsychotics, and distinct tolerability advantages over typical antipsychotics, which are reported to cause extrapyramidal symptoms (EPS) in 20–50% of patients. In addition, amisulpride is associated with significantly less weight gain than olanzapine and risperidone, does not increase body mass index, and favourably influences lipid profiles. In many patients with schizophrenia, adverse events impair adherence to treatment, and switching from typical or atypical antipsychotic therapy to amisulpride may be clinically appropriate. Observational drug-utilization studies suggest that many physicians switch to amisulpride because of fewer EPS and/or less weight gain and improved patient adherence. Cross-tapering (over 4 weeks), rather than abrupt cessation of pre-switch treatment, is preferred. Amisulpride has a low risk of drug-drug interactions, and, during cross-tapering, patients can remain on concurrent treatments (e.g. anticholinergics and antiparkinsonian agents) until the effective dosage has been reached. An appropriate amisulpride starting dose is 800 mg/day for patients with acute psychotic exacerbations, 400–800 mg/day for patients with predominantly positive symptoms, and 100–300 mg/day for predominantly negative symptoms. Amisulpride may be particularly suitable for clozapine-augmentation therapy in patients with refractory schizophrenia. Indeed, amisulpride is more effective than quetiapine as augmentation therapy in patients partially responsive to clozapine, and several prospective open-label studies and case series have reported promising results for amisulpride/clozapine combination therapy. In three prospective studies, addition of amisulpride 200–800 mg/day to clozapine significantly reduced mean scores on the Brief Psychiatric Rating Scale (BPRS) total (−33% to −35%), Clinical Global Impression (CGI)-Severity scale (−31%), Positive and Negative Syndrome Scale total (−22%), and Scale for the Assessment of Negative Symptoms (−34%). The proportion of responders (CGI score ≥3 or BPRS improvement >20%) was 71–86%. Retrospective case-series analyses have also reported im