Zuclopenthixol and haloperidol in patients with acute psychotic states. A double-blind, multi-centre study.

A double-blind, multi-centre study was carried out in 49 hospitalized patients with an acute psychosis or an exacerbation of a chronic psychosis to compare the wanted and unwanted effects of the neuroleptics, zuclopenthixol and haloperidol. Patients were allocated at random to receive treatment with one or other of the trial drugs for 8 weeks or until discharge. Five patients on zuclopenthixol and 6 on haloperidol were excluded from the efficacy analyses because they did not complete a minimum of 4-weeks' treatment. Dosage was chosen and adjusted to the individual patient's condition and response. The average daily doses in Week 4 were 33.5 mg and 10.3 mg, respectively. Clinical assessments, including CGI, BPRS and the UKU side-effect scale, were done at baseline, and after 1, 2, 4, 6 and 8 weeks of treatment or at discharge if the patient was discharged earlier than Week 8. Both treatments caused a significant reduction in scores with no between-group differences. More patients in the zuclopenthixol group were discharged early indicating slightly more rapid onset of action. Zuclopenthixol caused a significantly greater improvement in 'anxious-depression' factor score than haloperidol. The most frequent unwanted effects were extrapyramidal symptoms and there were no significant differences between the groups. The extrapyramidal symptoms tended to be transient in the zuclopenthixol group, but not in the haloperidol group. The study confirmed that both zuclopenthixol and haloperidol were effective drugs in the treatment of acute, psychotic patients. There was a trend towards a slightly more rapid onset of effect and a somewhat stronger anxiolytic-antidepressant effect by zuclopenthixol compared to haloperidol.

Enzyme inducing effects of phenobarbital on nitrazepam metabolism in dogs.

A 6-day peroral phenobarbital treatment of beagle dogs decreased clearly and significantly the mean AUC (1252 +/- 270 ng/ml/hr) of a single peroral dose of nitrazepam (1.5 mg/kg), as a sign of enzyme induction to one third (428 +/- 37 ng/ml/hr P < 0.05) in plasma and the concentration maximum (Cmax) (301 +/- 62 ng/ml/hr) to one third (110 +/- 15 ng/ml/hr, P < 0.05), respectively. The mean Kel, 0.36 +/- 0.04, increased to 0.54 +/- 0.04 (P < 0.05), respectively. An 11-day phenobarbital treatment decreased the mean AUC of nitrazepam further to one sixth (197 +/- 41 ng/ml/hr, P < 0.01) and the Cmax to one fifth (65 +/- 10 ng/ml/hr, P < 0.01), while the mean Kel increased from 0.36 +/- 0.04 to 0.65 +/- 0.02 (P < 0.001). The 12- day peroral nitrazepam treatment showed no sign of autoinduction as a single daily dose. The mean AUC of a single nitrazepam dose of the 1st day, 1290 +/- 256 ng/ml/hr increased after the 24-day nitrazepam treatment, to 3617 +/- 202 ng/ml/hr and after the 61-day treatment to 3379 +/- 321 ng/ml/hr. The mean maximum concentration (Cmax), 343 +/- 69 ng/ml/hr, increased to 727 +/- 52 ng/ml/hr, respectively.