A longitudinal therapeutic comparison between two prototypic neuroleptics (haloperidol and chlorpromazine) in matched groups of schizophrenics. Nontherapeutic interactions with trihexyphenidyl. Theoretical implications for potency differences.

The treatment process with two prototypic neuroleptics--haloperidol and chlorpromazine--and the nontherapeutic effects of trihexyphenidyl on this process were studied in carefully matched groups of ten schizophrenics each, using a "double-blind", repeated-measure, longitudinal research design. Measurements of various aspects of psychopathology, social participation and clinical indices of arousal were made periodically and objective test of cognition and attention were given. The two treatment groups were highly comparable in epidemiological and clinical terms and differed significantly during the baseline period in only one of the 39 parameters. Longitudinal nonparametric analyses showed that significant therepeutic changes tended to occur more quickly and involved a wider spectrum of schizophrenic phenomena with haloperidol than with chlorpromazine. Parametric analyses also indicated that at the completion of the study, haloperidol-treated patients had significant improvement in many more dimensions than the chlorpromazine-treated patients and that the changes with haloperidol were generally of greater magnitude. At the same time, chlorpromazine treatment seemed to be more susceptible to the antagonistic effects of trihexyphenidyl. No differential patterns of responses were noted for the two neuroleptics to provide any clinical validity to the distinction often made between "sedative" and "activating" neuroleptics. These data were in agreement with those from a previous comparative study which had a very different research design and a somewhat different type of schizophrenic population. The clinical and potency differences between the two neuroleptics were again explained on the basis of the fact that chlorpromazine has much stronger built-in anticholinergic properties, which may be acting in opposition to the antipsychotic activity. It was suggested that the degree of inherent anticholinergic activity may be an important determinant of potency differences among presently known neuroleptics. The possible role of cholinergic mechanisms in schizophrenia was discussed.