, Volume 43, Issue 2, pp 103–113

A comparative study of haloperidol and chlorpromazine in terms of clinical effects and therapeutic reversal with benztropine in schizophrenia. Theoretical implications for potency differences among neuroleptics

  • Man Mohan Singh
  • Stanley R. Kay
Original Investigations Human Pharmacology

DOI: 10.1007/BF00421012

Cite this article as:
Singh, M.M. & Kay, S.R. Psychopharmacologia (1975) 43: 103. doi:10.1007/BF00421012


In a double-blind, cross-over study, the comparative therapeutic effects of 6-week courses of two prototypic neuroleptics — haloperidol and chlorpromazine — and the reversal of those effects with benztropine were investigated in a group of 18 schizophrenics. Periodic measurements were made for 32 dimensions of psychopathology, social participation, span of attention, sleeplessness, pulse rate and neurological side effects. The results showed that haloperidol was generally a more effective drug over the period studied. This was particularly apparent in terms of social and emotional responsiveness, communicativeness and cognitive processes. The only superiority of chlorpromazine seemed to be that patients felt less dysphoric on it than they did on haloperidol. Haloperidol also proved to be more rapid in its action. The data failed to support the clinical validity of the distinction often made between “sedative” and “activating” neuroleptics. Consistent with previous reports, benztropine had the effect of diminishing therapeutic response to both neuroleptics. However, haloperidol again proved less susceptible to this effect. The slowness and lesser therapeutic efficiency of chlorpromazine and its greater susceptibility to benztropine reversal were all considered to be due to its built-in anticholinergic properties acting in opposition to its antipsychotic activity. The low potency of chlorpromazine-like drugs was attributed to their inherent anticholinergic characteristics. It was suggested that one of the factors determining potency differences among neuroleptics may be the degree of built-in anticholinergic activity.

Key words

SchizophreniaPsychopharmacologyHaloperidolChlorpromazineAnti-Parkinsonism DrugsBenztropineDrug InteractionsAnticholinergic EffectsNeuroleptic Potency“Sedative” Neuroleptic“Activating” Neuroleptic

Copyright information

© Springer-Verlag 1975

Authors and Affiliations

  • Man Mohan Singh
    • 1
  • Stanley R. Kay
    • 1
  1. 1.Clinical Psychopharmacology ServiceBronx Psychiatric CenterBronx