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Interaction with neuroleptics

There are contradictory reports in the literature about the effects of anticholinergic drugs on the blood level of neuroleptic drugs. Some studies show no effect (Forsman & Ohman, 1979; Itoh et al, 1980; Linnoila et al, 1980; Simpson et al, 1980), while others show reduction in neuroleptic drug levels (Loga et al, 1975; Rivera-Calimlim et al, 1973; 1976; Gautier et al, 1977; Morselli et al, 1980). There are also a few reports suggesting an increase in neuroleptic blood levels with anticholinergic drug administration (e.g. Kolakowska et al, 1976).

Johnstone et al (1983) did not find significant reduction in blood levels of flupenthixol following the addition of procyclidine, whereas Loga et al (1975) found that orphenadrine decreased levels of chlorpromazine when drugs were given together for a period of weeks. Similarly, Rivera-Calimlim et al (1976) found that chlorpromazine levels fell following introduction of benzhexol therapy but rose following anticholinergic withdrawal. Gautier et al (1971) also found similar results with benztropine, benzhexol and procyclidine. Anticholinergic drugs may influence the absorption of drugs from the gut (Rivera-Calimlim et al, 1976), moreover, anticholinergic drugs reduce intestinal motility and induce hepatic enzymes and thus may increase intestinal biodegradation and increase metabolism of neuroleptic drugs.

Although it has not yet been established whether therapeutic response of a neuroleptic is directly related to neuroleptic plasma levels (Perry et al, 1988), a reduction in therapeutic effect of neuroleptics has been noted by several authors (e.g. Singh & Smith, 1973: Ayd, 1974).