Therapeutic window of serum haloperidol concentration in acute schizophrenia and schizoaffective disorder.
Although several studies have been performed on the serum level-therapeutic effect relationship of neuroleptic drugs, the application of therapeutic drug-monitoring of neuroleptics is still a matter of controversy. Until now, haloperidol provided the most promising results. For this reason, an investigation of the dependence of clinical improvement on haloperidol serum levels was conducted in an acute psychiatric ward (Landeskrankenhaus Bernburg). In an open clinical trial haloperidol serum levels were measured in 57 acute schizophrenic patients for at least three weeks and correlated with clinical outcome (percent change of Brief Psychiatric Rating Scale, BPRS). A bisigmoidal model was used for data analysis. After three weeks of treatment, the major result proved to be a significant relationship between haloperidol serum level and therapeutic effect with pseudo-r2=0.316 and p=0.0031. Clinical improvement is enhanced by increasing haloperidol concentration up to about 10 ng/ml. It attains a maximum at about 10 ng/ml and decreases at haloperidol serum levels in a range of 10 ng/ml to 50 ng/ml. A simulation of this dependence of clinical improvement on serum levels, mediated by the variable dose design, can be excluded because of the results of a retrospective analysis of dosing behavior. Further evidence is thus provided for the dependence of therapeutic effect on the serum haloperidol concentration in acute schizophrenia. For practical application the position of a therapeutic window can be defined by a lower threshold level of about 5 ng/ml and an upper threshold of about 17 ng/ml. However, a maximal therapeutic effect is assured at 10 ng/ml. This should be the target value in serum level-guided dose adjustments.
Ulrich
S
S
Institute of Clinical Pharmacology, University Hospital, Otto-von-Guericke University, Magdeburg, Germany.
Neuhof
S
S
Braun
V
V
Meyer
F P
FP
D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood* / Q000627:therapeutic use; D016903:Drug Monitoring; D005260:Female; D006220:Haloperidol / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D011618:Psychotic Disorders / Q000097:blood* / Q000188:drug therapy; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy; D013997:Time Factors
D014150:Antipsychotic Agents; D006220:Haloperidol