Evidence for onset of antipsychotic effects within the first 24 hours of treatment.
OBJECTIVE
It is widely held that there is a delayed onset of antipsychotic action and that any early effects represent nonspecific behavioral effects. Recent research has shown that antipsychotic action begins within the first week. The authors tested the hypothesis that psychosis improves within the first 24 hours of antipsychotic treatment.


METHODS
In this multicenter, double-blind, placebo-controlled study, 311 patients with a diagnosis of schizophrenia spectrum disorder and an acute exacerbation were randomly assigned to receive 10 mg i.m. of olanzapine, 7.5 mg i.m. of haloperidol, or intramuscular placebo. Subjects were rated with structured rating scales (Positive and Negative Syndrome Scale and Clinical Global Impression) at baseline, 2 hours, and 24 hours.


RESULTS
The olanzapine and haloperidol groups showed greater resolution of overall symptoms than the placebo group; for the olanzapine group, this effect was evident at 2 hours. A factor analysis showed that an independent change in psychosis (which included conceptual disorganization, hallucinatory behavior, unusual thought content) was evident within the first 24 hours for both drugs. This improvement in core psychosis was not mediated unidirectionally by changes in nonspecific behavioral effects or other psychopathology.


CONCLUSIONS
These data suggest that the onset of antipsychotic action is early and that the magnitude of this action grows with time. This clinical reality calls into question some prevailing hypotheses regarding the mechanism of action of antipsychotics and suggests that antipsychotic action may be more proximally related to the blockade of dopamine transmission than was originally thought.
Kapur
Shitij
S
Centre for Addiction and Mental Health, 250 College St., Toronto, Ont., Canada M5R 1T8. shitij_kapur@camh.net
Arenovich
Tamara
T
Agid
Ofer
O
Zipursky
Robert
R
Lindborg
Stacy
S
Jones
Barry
B
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000494:pharmacology / Q000627:therapeutic use; D010054:Brief Psychiatric Rating Scale; D018492:Dopamine Antagonists / Q000494:pharmacology; D004311:Double-Blind Method; D005163:Factor Analysis, Statistical; D006220:Haloperidol / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007273:Injections, Intramuscular; D008875:Middle Aged; D000077152:Olanzapine; D010919:Placebos; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D013997:Time Factors; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D010919:Placebos; D001569:Benzodiazepines; D006220:Haloperidol; D000077152:Olanzapine