Risperidone augmentation of clozapine: a critical review.
OBJECTIVE
Atypical antipsychotics are frequently used as augmentation agents in clozapine-resistant schizophrenic patients. Risperidone (RIS) is the one most studied as a clozapine (CLZ) adjunct. The aim of this study is to critically review all published studies regarding the efficacy and safety of RIS as an adjunctive agent in CLZ-resistant schizophrenic or schizoaffective patients.


METHODS
A MEDLINE search from January 1988 to June 2005 was conducted. Identified papers were examined against several clinical, pharmacological and methodological parameters.


RESULTS
A total of 15 studies were found (2 randomized controlled trials, 3 open-label trials (OTs) and 8 case-studies (CSs)) comprising 86 schizophrenic or schizoaffective patients (mean age 38.4 years). Mean CLZ dosage during the combined treatment was 474.2 mg/day. Plasma CLZ levels were assessed in 62 patients (72.1%). RIS was added at a mean dosage of 4.6 mg/day for a mean of 7.9 weeks. Significant improvement in psychopathology was reported for 37 patients (43%). A lower RIS dosage and a longer duration of the trial seemed to be associated with a better outcome. Main side effects reported were: extrapyramidal symptoms or akathisia (9.3%), sedation (7%) and hypersalivation (5.8%).


CONCLUSIONS
Existing evidence encourages the use of RIS as an adjunctive agent in CLZ-resistant schizophrenic or schizoaffective patients.
Kontaxakis
Vassilis P
VP
Department of Psychiatry, University of Athens, Eginition Hospital, 74 Vas.Sophias Ave., 11528, Athens, Greece. bkont@cc.uoa.gr
Ferentinos
Panayotis P
PP
Havaki-Kontaxaki
Beata J
BJ
Paplos
Konstantinos G
KG
Pappa
Dimitra A
DA
Christodoulou
George N
GN
D014150:Antipsychotic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003024:Clozapine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004347:Drug Interactions; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004409:Dyskinesia, Drug-Induced / Q000453:epidemiology; D006801:Humans; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000523:psychology; D016032:Randomized Controlled Trials as Topic; D018967:Risperidone / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012798:Sialorrhea / Q000139:chemically induced; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D003024:Clozapine; D018967:Risperidone