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.
Method: 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.