High dosage haloperidol therapy in chronic schizophrenic patients: A double-blind study of clinical response, side effects, serum haloperidol, and serum prolactin

In a 12-weeks double-blind study high dosage versus standard dosage haloperidol therapy was evaluated in 23 male, chronic schizophrenic inpatients. The patients were relatively treatment-resistant and, in spite of traditional neuroleptic medication, were characterized by a moderate to severe degree of illness. At the end of the trial the dose of haloperidol in the standard dosage group was 12–36 mg/day (mean 15), in the high dosage group 10–240 mg/day (mean 103). No significant difference in therapeutic effect was found between the two groups as measured by the Brief Psychiatric Rating Scale and global assessment. About half the patients in both groups improved during the trial. A greater incidence of side effects was noticed in the high dosage group than in the standard group, especially in the form of sedation (5 of 12 patients), aggressive episodes (three patients), muscular weakness and tendency to fall (two patients), and epileptic attacks (one patient). The incidence of extrapyramidal phenomena showed fewer differences between the two groups. In addition, the high dosage group showed a temporary rise in serum alkaline phosphatase and serum aspartate-aminotransferase. There was a positive correlation between the dose of haloperidol and serum haloperidol, and between the haloperidol dose of up to 80 mg/day and serum prolactin. At higher doses prolactin response leveled off. Neither serum haloperidol nor serum prolactin showed any correlation to clinical response. It is concluded (1) that very high doses of haloperidol in only a few cases show any therapeutic advantage over haloperidol in standard doses; (2) that high dosage treatment has a higher incidence of side effects; and (3) that the serum concentrations of a given neuroleptic and of prolactin are of very limited value in the monitoring of neuroleptic treatment.