What is the lowest effective dose of haloperidol? Evidence from PET studies

The lowest effective dose of haloperidol is still a matter of debate. Recent PET studies show that: a) there is a threshold for clinical response around 60%-70% of D2 occupancy (Nordstrom ʹ93); and b) low plasma levels of haloperidol may be sufficient to reach these levels of D2 occupancy (Nyberg ʹ95). In light of these findings the purpose of this study was to determine the D2 dopamine receptor occupancy induced by low-dose haloperidol treatment in a prospective, controlled trial in patients in their first episode of psychosis. Seven patients with schizophrenia were treated with 2mg/day of haloperidol for two weeks. The D2 occupancy induced by haloperidol was measured using [11C]-raclopride and positron emission tomography; and plasma levels were measured using gas chromatography/mass spectrophotometer. Clinical response was measured using PANSS and CGI and side-effects were monitored using ESRS. Patients showed high levels of D2 occupancy (mean 66% ± 7%, range 53% to 74%). These occupancies were achieved with low plasma levels of haloperidol (mean 1.1 ± 0.4 ng/ml, range 0.6 to 1.5 ng/ml). At two weeks, five of the patients showed ‘much improvement’ as per the CGI, with a 45% improvement in the PANSS positive syndrome psychopathology and a 55% improvement in the PANSS negative syndrome psychopathology. In light of the recent clinical studies showing the efficacy of low dose (2-4 mg/d) of haloperidol, as well these PET findings, a strong argument can be made that clinicians should initiate treatment with low doses (equivalent of 2-4 mg/day of haloperidol), particularly in patients experiencing their first-episode of psychosis. Authors of Canada