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 > or =3 or BPRS improvement >20%) was 71-86%. Retrospective case-series analyses have also reported improved psychopathological state, reduced adverse events, and lower
clozapine dosage requirement with use of this combination. The pharmacological and clinical profiles of
amisulpride suggest that this agent is a viable clinical option when a change of
antipsychotic therapy is required in patients with
schizophrenia because of lack of efficacy, adverse events and poor adherence to treatment, or for augmentation of
clozapine in treatment-resistant illness.