The Effects of Coadministration of Haloperidol and Bethanechol on Plasma Haloperidol and Reduced Haloperidol Concentrations

Bethanechol, a cholinergic agonist, has been recommended for the management of peripheral anticholinergic side effects during the treatment of antipsychotic medications. But there have been few studies which have evaluated the drug interactions of antipsychotics and bethanechol, even the treatment effects of bethanechol on anticholinergic side effects. So the authors have evaluated whether psychopathology and plasma haloperidol and reduced haloperidol concentrations are significantly changed or not when bethanechol was administrated with maintained doses of haloperidol and other coadministrated drugs(such a benztropine). Also we have evaluated the abating effects of bethanechol on anticholinergic side effects during the treatment with haloperidol. Fifteen schizophrenics with higher than 5 of total score of anticholinergic side effects of 'Rating scale for side effect' were assigned to two groups, and bethanechol 30mg/day and 60mg/day were applied on each group for 4 weeks. The daily haloperidol dosages were fixed before 2 weeks of study. We assessed anticholinergic side effects by 'Rating scale for side effect' and psychopathology by BPRS, and plasma haloperidol and reduced haloperidol concentrations by HPLC at baseline, 2nd week and 4th week. The results were as followed. 1) There was no significant change of plasma haloperidol and reduced haloperidol concentration. 2) At baseline, the dosage of haloperidol showed significant correlation with the total score of anticholinergic side effect, but not at 2nd week and 4th week. 3) In 60mg/day group, dry mouth and the total score of anticholinergic side effects were significantly improved, but not in 30mg/day group. 4) There was no significant change of BPRS except withdrawal at 2nd week. These results suggest that coadministration of bethanechol influenced neither on psychopathology nor on plasma haloperidol and reduced haloperidol concentrations and that improved dry mouth and total score of anticholinergic side effects at 60mg/day.

Comparison of the Treatment Effect Between Higher and Lower Plasma Homovanillic Acid Groups in Schizophrenic Patients / 대한정신약물학회지

This study explored the differences of clinical response, plasma homovanllic acid concentration, haloperidol and reduced haloperidol concentration after 4 weeks haloperidol treatment between higher and lower baseline homovanllic acid concentration groups of schizophrenic patients. After a 2-weeks washout period, they entered the 4 week haloperidol treatment period. The psychopathology was assessed at baseline just before haloperidol trial and then at 1, 2, 4 week using Positive and Negative Syndrome Scale(PANSS). Also the measurement of plasma homovanillic acid(HVA), haloperidol(HP) and reduced haloperidol(RHP) levels were assessed with high performance liquid chromatography at the same time of PANSS assessments. There were no significant differences on the positive, negative, general symptom score of PANSS, haloperidol and reduced haloperidol levels at the end of 4-week between higher plasma HVA group(bsaeline pHVA> or =12.69ng/ml, 10 subjects) and lower plasma HVA group(bsaeline pHVA<12.69ng/ml, 9 subjects). In higher group, the treatment response mainly occured in 2 weeks after treatment, but in lower group, that occured therough 4 weeks. And in higher group, pHVA decresed constantly, but in lower group, pHVA did not changed in 4 weeks. There was significant correlation between plasma haloperidol levels and the clinical improvement(persentile improvement of PANSS positive, general symptom, total score) at the end of 4 week. But no significant correlation were found between plasma reduced haloperidol and RHP/HP ratio and clinical improvement. These results suggest that baseline HVA level is not a valuable therapeutic predictor but it is able to suggest that higher baseline pHVA group and lower group may have different pathophysiology.