Haloperidol: therapeutic window in schizophrenia.
Twenty-two schizophrenic inpatients were treated for 3 weeks with three randomly fixed oral doses of haloperidol (10, 20, or 30 mg). Analysis of the results by a nonlinear regression model revealed a curvilinear relationship between haloperidol levels in plasma and clinical response, as assessed on the Brief Psychiatric Rating Scale (pseudo-R2 = 0.85, F = 17.7, p < 0.001, correlation between coefficients ranged from 0.99 to -0.52). This curve defines roughly three drug level ranges (low, < 5.5 ng/ml; optimal, 5.5 to 14.4 ng/ml; and high or toxic, > 14.4 ng/ml), which are significant for clinical practice. Patients with high levels improve to a lesser extent or even worsen in negative symptoms, showing a nonstatistically significant trend to present more extrapyramidal symptoms. Our data thus support the existence of a therapeutic window for haloperidol. Schizophrenic patients with acute exacerbation and drug levels in this range would have a greater probability of global clinical improvement.
Palao
D J
DJ
Department of Psychiatry, Hospital Clínic i Provincial, Barcelona, Spain.
Arauxo
A
A
Brunet
M
M
Bernardo
M
M
Haro
J M
JM
Ferrer
J
J
Gonzalez-Monclus
E
E
D000328:Adult; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000097:blood / Q000175:diagnosis; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D012563:Schizophrenia, Paranoid / Q000097:blood / Q000188:drug therapy / Q000523:psychology; D012565:Schizophrenic Psychology
D006220:Haloperidol