Effectiveness of the selective D4 antagonist sonepiprazole in schizophrenia: a placebo-controlled trial.
BACKGROUND
Selective localization of dopamine D(4) receptors in the prefrontal cortex and preferential affinity of clozapine for the dopamine D(4) receptor over the D(2) receptor led to the hypothesis that the superior efficacy of clozapine may be mediated via blockade of the D(4) receptor. This hypothesis was tested by evaluating sonepiprazole, a selective D(4) dopamine antagonist, in schizophrenia patients.


METHODS
We treated 467 hospitalized schizophrenia patients with scores of > or = 60 on the Positive and Negative Syndrome Scale (PANSS) with sonepiprazole, olanzapine, or placebo once daily for 6 weeks. The primary efficacy end point was the mean change from baseline in the PANSS total score at 6 weeks. Secondary efficacy end points were the mean change from baseline in the PANSS factor scores, the Brief Psychiatric Rating Scale score, the Clinical Global Impressions Severity of Illness score, and the Calgary Depression Scale score.


RESULTS
No statistically significant differences were observed between placebo and any sonepiprazole dose on the primary or any secondary end point after 6 weeks of treatment. Statistically significant differences, favoring olanzapine over placebo, were observed on all efficacy end points but the Calgary Depression Scale.


CONCLUSIONS
Sonepiprazole was ineffective for the treatment of patients with schizophrenia.
Corrigan
Mark H
MH
Pharmacia Corporation, Kalamazoo, Michigan 01752, USA.
Gallen
Christopher C
CC
Bonura
M Luisa
ML
Merchant
Kalpana M
KM
D000293:Adolescent; D000328:Adult; D000342:Affective Symptoms / Q000209:etiology / Q000517:prevention & control*; D000368:Aged; D001569:Benzodiazepines / Q000008:administration & dosage*; D018492:Dopamine Antagonists / Q000008:administration & dosage*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D000077152:Olanzapine; D010879:Piperazines / Q000008:administration & dosage*; D010919:Placebos; D050638:Receptors, Dopamine D4; D012559:Schizophrenia / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D013449:Sulfonamides / Q000008:administration & dosage*; D000096926:Benzenesulfonamides
D001569:Benzodiazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D000077152:Olanzapine; D010879:Piperazines; D010919:Placebos; D050638:Receptors, Dopamine D4; D013449:Sulfonamides; C493599:DRD4 protein, human; C100448:sonepiprazole; D000096926:Benzenesulfonamides