Therapeutic Reversal With Benztropine in Schizophrenics

Trade names of drugs mentioned in this paper: haloperidol, Haldol (McNeil Laboratories, Fort Washington, Pa.); ehlorpromazine, Thorazine (Smith Kline and French, Philadelphia, Pa.); benztropine, Cogentin (Merck Sharp and Dohme, West Point, Pa.); diphenhydramine, Benadryl (Parke-Pavis, Detroit, Mich.). The effect of an anticholinergic antiparkinsonism drug, benztropine, on the therapeutic course of neuroleptie treatment in 18 schizophrenics was investigated in a double blind cross-over study involving haloperidol and ehlorpromazine. Significant therapeutic reversal was observed with benztropine in terms of the social, affective, and cognitive dysfunctions characteristically seen in schizophrenic psychosis. The hallucinatory behavior and disturbed attention were not so affected. The aspects of the clinical picture to show significant nontherapeutic change with benztropine differed with the stage of treatment and seemed to be determined by the kinetics of the therapeutic process. The effect was one of exacerbation of the disorder and not a toxic confusional state sometimes associated with anticholinergic drugs. The practical and theoretical significance of these findings was discussed. It was suggested that the benztropine reversal of therapeutic changes provided a valuable pharmacological model for understanding the neurobiological basis of schizophrenic decompensation and its restitution with neuroleptics. The reported data were considered as indirect evidence suggesting that cholinergic neuronal mechanisms are involved in both of these processes. It was speculated that these mechanisms may well be the cholinergic suppressor systems, such as the periventricular system, which function in reciprocal relationship with the facilitatory catecholamine pathways in the limbic organization and basal ganglia known to be affected by neuroleptics.