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
anti-cholinergic 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 difference among
neuroleptics may be the degree of built-in
anticholinergic activity.