TIMING OF ANTIPSYCHOTIC EFFECTS

Kapur S, Arenovich T, Agid O, et al. Evidence for onset of antipsychotic effects within the first 24 hours of treatment. Am J Psychiatry. 2005;162:939-946.

Summary

To test the hypothesis that antipsychotic agents can improve psychosis within the first 24 hours of treatment, a multicenter international study was conducted among 311 recently hospitalized patients with schizophrenia spectrum disorder. Before treatment, patients were exhibiting a psychotic episode with acute agitation. They were randomly assigned to receive intramuscular treatment with olanzapine (10 mg), haloperidol (7.5 mg), or placebo. Benzodiazepines were allowed as needed only after patients had received 1 or more injections of the study drugs or placebo. Of those who received active treatment, 15% required benzodiazepines.

Evaluation scales differentiated nonspecific behavioral symptoms (excitement, tension, mannerisms, suspiciousness, hostility, uncooperativeness) from symptoms of psychosis (conceptual disorganization, hallucinations, unusual thought content). Independent improvement in psychotic symptoms was seen with both drugs within 24 hours and within 2 hours in patients receiving olanzapine. The authors suggest that this response is not secondary to drug-induced changes in nonspecific behavioral symptoms. The findings question the hypothesis of delayed onset of action of antipsychotic agents.

Commentary

The results of this controlled double-blind study clearly support the authors' theory regarding the "early-onset" antipsychotic effect (within 24 hours) of olanzapine and haloperidol for inpatient populations. These results correlate with clinicians' experience in high-acuity settings, such as the psychiatric emergency service and the psychiatric inpatient unit.

Nevertheless, it is premature to conclude that an early-onset antipsychotic effect exists, in general, for these antipsychotic agents in patients with schizophrenia spectrum disorders. The criteria for use of these agents in inpatient care usually include acute agitation, positive symptoms, and danger to self or others. It is reasonable to conclude, however, that there may be subpopulations of patients within the spectrum of schizophrenic disorders who begin to respond within 24 hours of antipsychotic administration.

Although the authors of this study did not address this issue, there is a significant prevalence of substance use disorder in patients with schizophrenia (dual diagnosis). In particular, stimulant use can induce, trigger, or influence and exacerbate psychotic symptoms among such patients. The early onset of antipsychotic responses can partial- ly result from resolving stimulant-induced symptoms after antipsychotic treatment. Unless these substance- related effects are vigorously controlled for, it is impossible to interpret the effects of antipsychotic medication, as in this study, as specifically addressing the symptoms of schizophrenia.

Replication of this study in an outpatient setting among patients screened to ensure that they do not have dual diagnoses will help further clarify the onset of antipsychotic effects.

Christopher Chung, MD Associate Professor of Psychiatry Harbor-UCLA Medical Center Torrance, Calif