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

Abstract

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.

Nosological and Prognostic Distinctions in Schizophrenia: Pharmacological Validation in Terms of Therapeutic Antagonism between Anticholinergic Anti-Parkinsonism Drugs and Neuroleptics

“…All but one of the statistically significant findings indicated that AP inter ventions had been countertherapeutic and involved clinical parameters that would be recognized as being characteristic of schizophrenic psychosis and its response to neuroleptic treatment (4,22,23).…”

“…In studies II and III, a more detailed Psychopathology Rating Schedule was employed that included the previous items and used comparable criteria (22). A team o f specially trained raters, including psychologists, social workers and psychiatric nurses, gave the ratings (once a week in study 1 and once every other week in studies II and III) on the basis o f a semistructured clinical interview, usually lasting an hour or more.…”

Component structure of the Positive And Negative Syndrome Scale (PANSS) in patients with recent-onset schizophrenia and spectrum disorders

“…The PANSS, which includes a positive scale, a negative scale and a general psychopathology scale, is based on 18 items of the Brief Psychiatric Rating Scale (BPRS; Beller and Overall 1984) and 12 items of the Psychopathology Rating Schedule (PRS; Singh and Kay 1975).…”

Drug Interactions in Psychiatry

“…While antiparkinsonian drugs, by decreasing ab sorption and consequently serum levels, may interfere with the therapeutic ac tion of neuroleptics (Singh and Ray, 1975;Rivera-Calimlim, 1976), tricyclic antidepressants, by increasing serum levels, enhance their pharmacological ef fects. Nevertheless, simultaneous administration of an antiparkinsonian drug and a tricyclic antidepressant may intensify the anticholinergic action, of the neuro leptic such that confusional state, bladder atonia, or paralytic ileus may occur.…”