@article{3096994,
    title = "Randomized controlled augmentation trials in clozapine-resistant
schizophrenic patients: a critical review",
    author = "Kontaxakis, VP and Ferentinos, PP and Havaki-Kontaxaki, BJ and Roukas, and DK",
    journal = "European Psychiatry",
    year = "2005",
    volume = "20",
    number = "5-6",
    pages = "409-415",
    publisher = "ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER",
    issn = "0924-9338",
    doi = "10.1016/j.eurpsy.2004.12.007",
    keywords = "schizophrenia; clozapine-resistant; double-blind; controlled;
augmentation; adjunctive",
    abstract = "Approximately 40-70% of treatment-resistant schizophrenic patients fail
to benefit from clozapine monotherapy or are partial responders. During
the last years several clozapine adjunctive agents have come into
clinical practice. This study aims to critically review all published
randomized, double-blind, placebo-controlled clinical trials (RCTs)
regarding the efficacy and safety of adjunctive agents in
dozapine-resistant schizophrenic or schizoaffective patients. A MEDLINE
search for RCTs on clozapine adjunctive agents published from January
1980 to February 2004 was conducted. All identified papers were
critically reviewed and examined against several methodological features
as well as clinical and pharmacological parameters. Eleven trials
including 270 patients, partial or non-responders to clozapine, assessed
the efficacy of sulpiride, lithium, lamotrigine, fluoxetine, glycine,
D-serine, D-cycloserine and ethyl-eicosapentanoate (E-EPA) as clozapine
adjuncts. There were eight parallel-group and three crossover trials.
The inclusion criteria varied widely. The duration as well as the dosage
of clozapine monotherapy were reported adequate in only one trial.
Plasma clozapine levels were assessed in only three trials. Main
side-effects reported were hypersalivation, sedation, diarrhea, nausea,
hyperprolactinaema. The outcome favored clozapine augmentation with
sulpiride, lamotrigine and E-EPA. Lithium was shown to benefit only
schizoaffective patients. However, the methodological shortcomings of
trials analyzed limit the impact of evidence provided. (c) 2005 Elsevier
SAS. All rights reserved."
}