Clozapine augmented with risperidone in the treatment of schizophrenia: a randomized, double-blind, placebo-controlled trial.
OBJECTIVE
The authors evaluated the efficacy and safety of augmenting clozapine with risperidone in patients with treatment-resistant schizophrenia.


METHODS
In a randomized, double-blind, placebo-controlled 12-week trial, 40 patients unresponsive or partially responsive to clozapine monotherapy received a steady dose of clozapine combined with either placebo (N=20) or up to 6 mg/day of risperidone (N=20). Patient psychopathology was assessed at 2-week intervals with the Brief Psychiatric Rating Scale (BPRS) and the Scale for the Assessment of Negative Symptoms (SANS), among other measures. Movement disorders were assessed with the Simpson-Angus Rating Scale.


RESULTS
From baseline to week 6 and week 12, mean BPRS total and positive symptom subscale scores were reduced significantly in both groups, but the reductions were significantly greater with clozapine/risperidone treatment. Reductions in SANS scores were also significantly greater with clozapine/risperidone treatment than with clozapine/placebo. The adverse event profile for clozapine/risperidone treatment was similar to that for clozapine/placebo. Simpson-Angus Rating Scale scores were lower with clozapine/risperidone treatment throughout the trial but increased to approach those of clozapine/placebo treatment at week 12. Clozapine/risperidone treatment did not induce additional weight gain, agranulocytosis, or seizures compared with clozapine/placebo treatment.


CONCLUSIONS
In patients with a suboptimal response to clozapine, the addition of risperidone improved overall symptoms and positive and negative symptoms of schizophrenia. The combination appears to be safe and well tolerated. Augmentation of clozapine with risperidone may provide additional clinical benefit for patients who are nonresponsive or only partially responsive to clozapine alone.
Josiassen
Richard C
RC
The Arthur P. Noyes Research Foundation, Norristown State Hospital, Norristown, PA 19401, USA. richardjosiassen@noyesfoundation.net
Joseph
Ashok
A
Kohegyi
Eva
E
Stokes
Sudhir
S
Dadvand
Mahmood
M
Paing
Wynn Wynn
WW
Shaughnessy
Rita A
RA
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D010054:Brief Psychiatric Rating Scale; D003024:Clozapine / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D010919:Placebos; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D010919:Placebos; D003024:Clozapine; D018967:Risperidone