Pharmacokinetic considerations in antipsychotic augmentation strategies: How to combine risperidone with low-potency antipsychotics.

Paulzen, Michael; Schoretsanitis, Georgios; Stegmann, Benedikt; Hiemke, Christoph; Gründer, Gerhard; Schruers, Koen R J; Walther, Sebastian; Lammertz, Sarah E; Haen, Ekkehard (2017). Pharmacokinetic considerations in antipsychotic augmentation strategies: How to combine risperidone with low-potency antipsychotics. Progress in neuro-psychopharmacology & biological psychiatry, 76, pp. 101-106. Elsevier 10.1016/j.pnpbp.2017.03.002

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OBJECTIVES

To investigate in vivo the effect of low-potency antipsychotics on metabolism of risperidone (RIS).

METHODS

A therapeutic drug monitoring database containing plasma concentrations of RIS and its metabolite 9-OH-RIS of 1584 patients was analyzed. Five groups were compared; a risperidone group (n=842) and four co- medication groups; a group co-medicated with chlorprothixene (n=67), a group with levomepromazine (n=32), a group with melperone (n=46), a group with pipamperone (n=63) and a group with prothipendyl (n=24). Plasma concentrations, dose-adjusted plasma concentrations (C/D) of RIS, 9-OH-RIS and active moiety (RIS+9-OH-RIS; AM) as well as the metabolic ratios (9-OH-RIS/RIS; MR) were computed.

RESULTS

Differences in plasma concentrations were detected for AM and RIS. Pairwise comparisons revealed significant findings; RIS plasma concentrations were higher in co-medication groups than in monotherapy group. Chlorprothixene- and prothipendyl- medicated patients demonstrated no other differences. In the levomepromazine and melperone group plasma and C/D concentrations of AM and RIS were higher, while MRs were lower. For pipamperone, differences included higher C/D values of RIS and lower MRs.

CONCLUSIONS

Alterations of risperidone metabolism suggest pharmacokinetic interactions for levomepromazine and melperone. In the pipamperone-group, lower MRs as well as higher plasma and C/D levels of RIS suggest potential interactions.

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