A Multidose Study of Haloperidol Decanoate in the Maintenance Treatment of Schizophrenia
Kane JM, Davis JM, Schooler N, Marder S, Casey D, Brauzer B, Mintz J, Conley R ;
Commented by , 13 Jun 2002
Aim of the study
The authors tried to find out the optimum haloperidol decanoate dose for the maintenance treatment of schizophrenia.
Method
For this, a multicenter, double-blind study was conducted. 105 outpatients were randomly assigned to four fixed doses of haloperidol decanoate. The doses used were 25, 50, 100, and 200 mg given intramuscularly once per month. The patients were treated for one year or until a relapse occurred.
During the first 4 weeks of treatment oral haloperidol could be added if necessary. Benztropine mesylate, up to 8mg/day and propanolol were allowed for the treatment of extrapyramidal side-effects. Symptoms were rated monthly with the Brief Psychiatric Rating scale and the Clinical Global Impression scale. Extrapyramidal side-effects were evaluated with the Simpson-Angus Rating Scale and tardive dyskinesia were evaluated with the AIMS. Symptomatic exacerbation ("relapse") was defined as an increase on one psychotic item of at least 2 scale points.
Results
The mean age at study entry was 39 years, overall the sample was predominantly male, with equal representations of Caucasians and African Americans. The rates of symptomatic exacerbations were 15% in the 200-mg group, 23% with 100 mg, 25% with 50 mg, and 60% with 25 mg. The relapse risk in the 25mg group was thus significantly higher than in the other groups. No significant differences in outcome were found between the groups treated with 200, 100, and 50 mg.
Among the patients who completed the trial with no symptomatic exacerbation, there were no differences between dose groups on measures of psychopathology at the final rating point. In the 25 mg group there were fewer extrapyramidal side-effects, but no differences were found between the other dose groups.
Discussion
One of the problems of conventional antipsychotics such as haloperidol is that in contrast to the atypical antipsychotics there optimum doses are not well defined. As long as no atypical antipsychotic is available as a well established depot formulation, high quality scientific information about the optimum haloperidol decanoate dose for maintenance treatment is very important.
The results of this study suggest that the 200 mg/month dose of haloperidol decanoate is associated with the lowest rate of symptomatic exacerbation (15%) with minimal increased risk of adverse effects or subjective discomfort in comparison to 100 or 50 mg. At the same time, the rates of worsening with 100 mg (23%) and 50 mg (25%) were not significantly greater than that seen with 200 mg.
These results provide some guidance as to effective dose ranges of haloperidol decanoate. They can also be used as a benchmark for future trials about depot formulations of atypical antipsychotics.