HALOPERIDOL PLASMA-LEVELS AND DOSE OPTIMIZATION

Objective: This study was designed to test the practical utility of ha loperidol plasma level determinations in the management of schizophren ic patients who show poor initial responses to haloperidol. Method: In patients with acute exacerbations of DSM-III schizophrenia (N=66) were randomly assigned to receive fixed haloperidol doses intended to achi eve plasma levels of 8-18 ng/ml or of 25-35 ng/ml. Patients whose scor es on the Brief Psychiatric Rating Scale (BPRS) failed to improve by a t least 30% at the end of 3 weeks were then subject to dose reassignme nt. Results: Among the patients who completed the fir`st phase of the protocol, 30 had steady-state haloperidol plasma levels of less than 1 8 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 38% impr ovement significantly favored the two lower plasma level groups, altho ugh 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 random ly assigned to receive lower and higher doses, respectively. Those who se 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 c ountertherapeutic. In particular, increases in dose beyond this level are not efficacious for patients who have not responded to lower doses .