Lower dosages of risperidone needed in older patients co-treated with perazine for ascariasis or pinworm?



If you have kept up with the pharmacokinetics of risperidone, your answer to the question in our title will likely be “Yes.” An anthelminthic prescribed for ascariasis and pinworm species in animals and man and an early (late Fifties era with some persistence to that of today), antipsychotic, perazine has been reported to inhibit CYPs 2D6 and 3A4, and therefore affords rationale for an affirmative expectation of interactivity between perazine and risperidone, a substrate of both CYPs 2D6 and 3A4.

A recently reported study by University of Groningen researchers (M. Paulzen and colleagues, British Journal of Clinical Pharmacology 83(8):1666-1675. 2017) provides the most recent corroboration. That by E. Molden and colleagues (Basic Clinical Pharmacology and Toxicology 119(5):470-475), reviewed elsewhere herein provides the same, apropos of risperidone, for an even less exceptionable inverse relationship between ageing and risperidone metabolism.

The recently reported study by Paulzen and colleagues (op. cit.) was a retrospective comparison of 40 patients receiving risperidone monotherapy and a group of 16 patients receiving perazine (for microbial infections) coadministered with risperidone for psychotic disorders. The patients co-treated with perazine and risperidone showed higher risperidone and active moiety (summed risperidone and 9-hydroxyrisperidone) bioavailabilities than did patients receiving risperidone monotherapy. Perazine-associated increases in risperidone and active moiety increments appeared unrelated to incommensuracy of older patients in the perazine-risperidone-treated group. (No patient treated with coadministered perazine or risperidone is reported to have suffered severe adverse effects of risperidone over the short duration of pharmacokinetic drug-drug interactivity.)

The authors’ findings suggest patients taking perazine for ascariasis or pinworm may need reduced dosages of risperidone to develop therapeutic antipsychotic bioavailabilities of risperidone (the pharmacokinetics of perazine, with less potent antipsychotic activity, is not reported affected by risperidone). (Their study represents one of numerous instances of polytherapy with pharmacokinetically interactive drugs, perforce required by the presence of more than one disease process. Perhaps it will help gainsay arbitrary and erroneous representation of clinicians prescribing “polypharmacy” as neglecting to weigh risks of drug-drug interactions with those of insufficiently treated illness. In psychiatry, the analogical equivalent of anthelminthic treatment and psychotic disorder is polytherapy for principal psychiatric diagnosis and psychiatric comorbidity, which, if insuffiently treated, eventuates in inferior global outcome and quality of life during follow-up of the principal psychiatric diagnosis.


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