Effectiveness of antipsychotic polypharmacy for patients with treatment refractory schizophrenia: an open-label trial of olanzapine plus risperidone for those who failed to respond to a sequential treatment with olanzapine, quetiapine and risperidone.
OBJECTIVE
To evaluate the effectiveness of antipsychotic polypharmacy in a methodologically sound manner.


METHODS
In this open-label study, 17 patients with treatment-refractory schizophrenia, who failed to respond to a sequential monotherapy with olanzapine, quetiapine and risperidone, were subsequently treated with a combination therapy with olanzapine plus risperidone for at least 8 weeks.


RESULTS
Seven responded according to the primary endpoint defined as the post-treatment Brief Psychiatric Rating Scale being less than 70% of the pretreatment values, and they were classified as such an average of 10 weeks after the initiation of polypharmacy. Two of them were successful in a later conversion to monotherapy. None dropped out prematurely. Four (out of 13 inpatients) got better enough to be discharged from the hospital, while six patients did not show any response. The Global Assessment of Functioning score improved from 37.1 to 53.0 in responders (mean maximum dose: olanzapine 12.9 mg; risperidone 3.14 mg), while it showed non-significant changes among others (mean maximum dose: olanzapine 14.5 mg; risperidone 5.50 mg). Body weight, prolactin, and total cholesterol increased significantly.


CONCLUSIONS
Antipsychotic polypharmacy might be sometimes helpful for difficult populations but at the cost of adverse effects. More studies of antipsychotic combination therapy versus clozapine, augmentation strategies or tenacious longer- term monotherapy are warranted for refractory schizophrenia.
Department of Neuro-Psychiatry, School of Medicine, Keio University, Shinanomachi, Shinjuku-ku, Tokyo, Japan. takefumi@oak.dti.ne.jp
Takefumi
T
Suzuki
Hiroyuki
H
Uchida
Koichiro
K
Watanabe
Shinichiro
S
Nakajima
Kensuke
K
Nomura
Hiroyoshi
H
Takeuchi
Akira
A
Tanabe
Gohei
G
Yagi
Haruo
H
Kashima
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001569:Benzodiazepines / Q000008:administration & dosage*; D003987:Dibenzothiazepines / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D019338:Polypharmacy; D000069348:Quetiapine Fumarate; D018967:Risperidone / Q000008:administration & dosage*; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D018967:Risperidone; D000077152:Olanzapine