Augmentation strategies of clozapine with antipsychotics in the treatment of ultraresistant schizophrenia.
BACKGROUND
Approximately 40% to 70% of neuroleptic-resistant schizophrenic patients are nonresponders to clozapine. Several clozapine augmentation strategies have come into clinical practice although often without evidence-based support. Among these strategies, the combined use of clozapine with another antipsychotic has been reported for up to 35% of patients receiving clozapine.


OBJECTIVE
The purposes of the present work were to (1) review the available literature on the efficacy and safety of the clozapine augmentation with another antipsychotic using a MEDLINE search of the literature from 1978 to December 2005 and (2) to propose an operational definition of schizophrenia refractory to clozapine ("ultraresistant schizophrenia") for the implementation and homogenization of future therapeutic trials.


CONCLUSIONS
Case controls and open clinical trials largely dominate the literature, and there are only 4 double-blind studies of clozapine augmentation with antipsychotics. The results of these studies are somewhat discrepant. Moreover, the heterogeneity of definitions of resistance to clozapine, of outcome measures and of dose and duration of pharmacological trials is a major limitation for drawing conclusions.
Mouaffak
Fayçal
F
Service Hospitalo-Universitaire de Santé Mentale et de Thérapeutique, Université René Descartes and INSERM E0117, Sainte-Anne Hospital, 7 rue Cabanis, 75014 Paris, France. mouaffakf@yahoo.fr
Tranulis
Constantin
C
Gourevitch
Raphaël
R
Poirier
Marie-France
MF
Douki
Saida
S
Olié
Jean-Pierre
JP
Lôo
Henri
H
Gourion
David
D
D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002746:Chlorpromazine / Q000627:therapeutic use; D003024:Clozapine / Q000627:therapeutic use*; D004351:Drug Resistance / Q000502:physiology*; D004357:Drug Synergism; D006801:Humans; D016239:MEDLINE / Q000706:statistics & numerical data; D015201:Meta-Analysis as Topic; D017063:Outcome Assessment, Health Care; D017410:Practice Guidelines as Topic; D012196:Review Literature as Topic; D012559:Schizophrenia / Q000188:drug therapy*; D013469:Sulpiride / Q000627:therapeutic use
D014150:Antipsychotic Agents; D013469:Sulpiride; D003024:Clozapine; D002746:Chlorpromazine