Optimal haloperidol dosage for first episode schizophrenia

There continues to be much uncertainty about what dosages of antipsychotic medication are optimal for the treatment of a first episode of schizophrenia. We investigated this question in a prospective controlled 4 week clinical trial involving a stepwise increase in haloperidol dosage. Patients were all suffering from a first episode of non-affective psychosis. “Optimal dosage” was established as that dosage at which there was either: a) clinical improvement defined as a minimum of 15% decrease on the total PANSS score, or b) the onset of extrapyramidal symptoms (EPS). Treatment began with haloperidol 2mg/day for 1 week and was increased on a weekly basis to 5mg/day, 10mg/day and 20 mg/day. If either criteria for “optimal dosage” was met after 1 week on any given dosage, then this dosage was continued for the remainder of the 4 week trial. Thirty-three of 36 patients entered into the study completed the full 4 week study (mean age=26.7 ± 5.8 yrs; 19 male, 14 female). Fourteen patients had an “optimal dosage” of 2 mg/day (14 responders, 0 EPS) while 9 patients were maintained on 5 mg/day (3 responders, 6 EPS), 7 patients on 10 mg/day (0 responders, 7 EPS) and 3 patients on 20 mg/day (2 responders, 1 EPS). The percent improvement on total PANSS at 4 weeks for those who were maintained on 2, 5, 10, and 20 mg was 74%, 47%, 25% and 33%, respectively. Twenty-five of 33 patients met criteria for clinical improvement at 4 weeks of whom 19 had plasma haloperidol levels which were less than 5 ng/ml. These findings suggest that patients being treated for a first episode of non-affective psychosis may respond to haloperidol dosages well below the commonly quoted therapeutic range. This is consistent with recent PET evidence confirming that high levels of D2 occupancy (>60%) are observed with dosages of haloperidol as low as 2mg/day. Support for this work was provided by the National Health Research and Development Program of Canada and the Ontario Mental Health Foundation.