Haloperidol plasma levels and dose optimization.
OBJECTIVE
This study was designed to test the practical utility of haloperidol plasma level determinations in the management of schizophrenic patients who show poor initial responses to haloperidol.


METHODS
Inpatients with acute exacerbations of DSM-III schizophrenia (N = 66) were randomly assigned to receive fixed haloperidol doses intended to achieve plasma levels of 8-18 ng/ml or of 25-35 ng/ml. Patients whose scores on the Brief Psychiatric Rating Scale (BPRS) failed to improve by at least 30% at the end of 3 weeks were then subject to dose reassignment.


RESULTS
Among the patients who completed the first phase of the protocol, 30 had steady-state haloperidol plasma levels of less than 18 ng/ml, and 22 had levels that exceeded 25 ng/ml; 14 had intermediate plasma levels of 18-25 ng/ml. A survival analysis of time to 30% improvement significantly favored the two lower plasma level groups, although side effect ratings did not differ. Of the 30 patients whose BPRS scores failed to improve by 30% after 3 weeks, 11 and five were randomly assigned to receive lower and higher doses, respectively. Those whose dose was lowered experienced significantly more improvement in the subsequent weeks than did those whose dose was increased.


CONCLUSIONS
Haloperidol plasma levels that substantially exceed 18 ng/ml may be countertherapeutic. In particular, increases in dose beyond this level are not efficacious for patients who have not responded to lower doses.
Coryell
W
W
Department of Psychiatry, University of Iowa College of Medicine, Iowa City 52242, USA.
Miller
D D
DD
Perry
P J
PJ
D000293:Adolescent; D000328:Adult; D010054:Brief Psychiatric Rating Scale; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D012559:Schizophrenia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D017211:Treatment Failure; D016896:Treatment Outcome
D006220:Haloperidol