Risperidone metabolism

Spina E, Avenoso A, Scordo MG, Ancione M, Madia A, Gatti G, Perucca E. Inhibition of risperidone metabolism by fluoxetine in patients with schizophrenia a clinically relevant pharmacokinetic drug interaction. J Clin Psychopharmacol 2002 22(4) 419-23. 

Bork JA, Rogers T, Wedlund PJ, de Leon J. A pilot study on risperidone metabolism the role of cytochromes P450 2D6 and 3A. J Clin Psychiatry 1999 60(7) 469-76. 

Nakagami T, Yasui-Furukori N, Saito M, Mihara K, De Vries R, Kondo T, Kaneko S. Thioridazine inhibits risperidone metabolism a clinically relevant drug interaction. J Clin Psychopharmacol 2005 25 89-91. 

Suzuki Y, Fukui N, Watanabe J, Ono S, Sugai T, Tsuneyama N, Inoue Y, Someya T. Gender differences in the relationship between the risperidone metabolism and the plasma prolactin levels in psychiatric patients. Prog Neuropsycho-pharmacol Biol Psychiatry 2010 34 1266-8. 

Suzuki Y, Fukui N, Tsuneyama N, Watanabe J, Qno S, Sugai T, et al. Effect of the cytochrome P450 2D6 10 allele on risperidone metabolism in Japanese psychiatric patients. Hum Psychopharmacol 2012 27(l) 43-6. 

Aripiprazole shares a similar metabolic profile to risperidone, being metabolized by CYP2D6 and 3A4 (Kubo etal, 2005). Few studies exist to compare and contrast aripiprazole effects in different ethnic groups. A recent study indicated that Chinese... 

Risperidone and its active metabolite 9-OH-resperidone are metabolized by CYP2D6. Polymorphic metabolism should be considered in those with side effects at low doses (approximately 40% of African Americans and Asians can have increased side effects from risperidone and other drugs metabolized through CYP2D6). 

This group includes risperidone, quetiapine, olanzapine, ziprasidone, and aripiprazole. But all these agents cause dose-related EPS and appear in general more likely to cause diabetes and other metabolic problems than some of the older drugs (see Duggan et ah, 2005). 

Risperidone is metabolized primarily by CYP 2D6 (Byerly and De-Vane 1996). Medications that inhibit this enzyme, such as many of the SSRls, cause increases in plasma risperidone levels. Pharmacodynamic interactions may occur when risperidone is combined with medications that share a similar physiological effect, such as orthostatic hypotension. 

The receptor properties of quetiapine are similar to those for olanzapine and risperidone. This medication is rapidly absorbed, reaching peak plasma concentrations in 1.5 hours. It is metabolized by the liver. 

Phenytoin, an enzyme inducer, can reduce clozapine plasma levels. There have been two reported cases of risperidone causing an increase in clozapine plasma levels however, because this agent is not an inhibitor of 1A2, the mechanisms for this increase are unclear. Nefazodone administered with clozapine has had minimal effects on clozapine s metabolism (329). 

Insulin resistance is a major but not necessary risk factor for type 2 diabetes. Glucose metabolism in 36 out-patients with schizophrenia aged 18-65 years taking clozapine (n — 12), olanzapine (n — 12), or risperidone (n = 12) has been examined in a cross-sectional study... 

Meyer JM. A retrospective comparison of weight, lipid, and glucose changes between risperidone- and olanzapine-treated inpatients metabolic outcomes after 1 year. J Clin Psychiatry 2002 63(5) 425-33. 

Cyt 2D6 metabolizes haloperidol, risperidone, thioridazine, sertindole, olanzapine and clozapine common substrates - fluoxetine, paroxetine, sertraline, venlafaxine, amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, propranolol, metoprolol, timolol, codeine, encainide, flecanide. Common inhibitors - paroxetine, sertraline, fluoxetine. 

Peter Liddle and his colleagues (2000) used positron emission tomography (PET) to study the effects of risperidone on the rate of metabolism on the ventral striatum, thalamus, and frontal cortex. Their subjects were eight neuroleptic-naive patients diagnosed with their first episodes of schizophrenia. 

Moreover, according to Fiddle et al. (2000), after six weeks treatment with risperidone, the decreases in frontal lobe metabolism were more extensive. In other words, the risperidone produced a progressive chemical lobotomy with suppression of frontal lobe function. 

---