Clinical Drug Investigation

, Volume 28, Issue 8, pp 465–477 | Cite as

Practical Issues with Amisulpride in the Management of Patients with Schizophrenia

  • Luca Pani
  • José M. Villagrán
  • Vassilis P. Kontaxakis
  • Köksal Alptekin
Review Article

Abstract

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 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.

Keywords

Schizophrenia Clozapine Risperidone Olanzapine Ziprasidone 

Notes

Acknowledgements

Dr Alptekin serves as a consultant, advisor and/or lecturer for sanofi-aventis, Lundbeck, Janssen, Pfizer, AstraZeneca, Bristol-Myers Squibb, Sanovel and Eczacibaşi. Over the last 2 years Prof. Pani has served as a consultant, advisor and/or lecturer for AstraZeneca, Bristol-Myers Squibb, Janssen, Johnson & Johnson, Lundbeck, Organon-Schering Plough, Pfizer and sanofi-aventis. The other authors have no conflicts of interest that are directly relevant to the content of this review.

Editorial support for the preparation of this manuscript was provided by Wolters Kluwer Health Medical Communications. This assistance was funded by sanofi-aventis.

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Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Luca Pani
    • 1
    • 2
  • José M. Villagrán
    • 3
  • Vassilis P. Kontaxakis
    • 4
  • Köksal Alptekin
    • 5
  1. 1.Institute of Biomedical Technologies, National Research Council (CNR)MilanItaly
  2. 2.PharmaNess ScarlSardegna RicerchePula (Cagliari)Italy
  3. 3.Psychiatric Hospitalization UnitJerez Hospital, Andalusian Health ServiceCádizSpain
  4. 4.University of Athens, Eginition HospitalAthensGreece
  5. 5.Department of Psychiatry, School of MedicineUniversity of Dokuz EylülIzmirTurkey

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