Effect of CYP2D6 on Risperidone Pharmacokinetics and Extrapyramidal Symptoms in Healthy Volunteers: Results from a Pharmacogenetic Clinical Trial

• Ravyn D , RavynV, LowneyR, NasrallahHA. CYP450 pharmacogenetic treatment strategies for antipsychotics: a review of the evidence. Schizophr. Res.149 , 1–14 (2013).
   PubMed Web of Science ®Google Scholar
• Yasui-Furukori N , HidestrandM, SpinaE et al. Different enantioselective 9-hydroxylation of risperidone by the two human CYP2D6 and CYP3A4 enzymes. Drug Metab. Dispos. 29 , 1263–1268 (2001).
   PubMed Web of Science ®Google Scholar
• Kang RH , JungSM, KimKA et al. Effects of CYP2D6 and CYP3A5 genotypes on the plasma concentrations of risperidone and 9-hydroxyrisperidone in Korean schizophrenic patients. J. Clin. Psychopharmacol. 29 , 272–277 (2009).
   PubMed Web of Science ®Google Scholar
• Llerena A , BereczR, DoradoP et al. QTc interval, CYP2D6 and CYP2C9 genotypes and risperidone plasma concentrations. J. Psychopharmacol. 18 , 189–193 (2004).
   PubMed Web of Science ®Google Scholar
• de Leon J , SusceMT, PanRM et al. The CYP2D6 poor metabolizer phenotype may be associated with risperidone adverse drug reactions and discontinuation. J. Clin. Psychiatry 66 , 15–27 (2005).
   PubMed Web of Science ®Google Scholar
• Troost PW , LahuisBE, HermansMH et al. Prolactin release in children treated with risperidone: impact and role of CYP2D6 metabolism. J. Clin. Psychopharmacol. 27 , 52–57 (2007).
   PubMed Web of Science ®Google Scholar
• Barteček R , JuřicaJ, ZrůstováJ et al. Relevance of CYP2D6 variability in first-episode schizophrenia patients treated with risperidone. Neuro Endocrinol. Lett. 33 , 236–244 (2012).
   PubMed Web of Science ®Google Scholar
• Kobylecki CJ , JakobsenKD, HansenT et al. CYP2D6 genotype predicts antipsychotic side effects in schizophrenia inpatients: a retrospective matched case–control study. Neuropsychobiology59 , 222–226 (2009).
   PubMed Web of Science ®Google Scholar
• Locatelli I , KastelicM, KoprivsekJ et al. A population pharmacokinetic evaluation of the influence of CYP2D6 genotype on risperidone metabolism in patients with acute episode of schizophrenia. Eur. J. Pharm. Sci. 41 , 289–298 (2010).
   PubMed Web of Science ®Google Scholar
• Tonda ME , GuthrieSK. Treatment of acute neuroleptic-induced movement disorders. Pharmacotherapy14 , 543–560 (1994).
   PubMed Web of Science ®Google Scholar
• Kapur S , ZipurskyRB, RemingtonG. Clinical and theorical implications of 5-HT2 and D2 receptor occupancy of clozapine olanzapine and risperidone in schizophrenia. Am. J. Psychiatry156 , 286–293 (1999).
   PubMed Web of Science ®Google Scholar
• Mas S , BernardoM, GassóP et al. A functional variant provided further evidence for the association of ARVCF with schizophrenia. Am. J. Med. Genet. B Neuropsychiatr. Genet. 153 , 1052–1059 (2010).
   Google Scholar
• Mas S , GassòP, AlvarezS, ParelladaE, BernardoM, LafuenteA. Intuitive pharmacogenetics: spontaneous risperidone dosage is related to CYP2D6, CYP3A5 and ABCB1 genotypes. Pharmacogenomics J.12 , 255–259 (2012).
   PubMed Web of Science ®Google Scholar
• Crescenti A , MasS, GassoP, BaigetM, BernardoM, LafuenteA. Simultaneous genotyping of CYP2D6 *3,*4,*5 and *6 polymorphisms in a Spanish population through multiplex long-PCR and minisequencing multiplex single base extension (SBE) analysis. Clin. Exp. Pharmacol. Physiol.34 , 992–997 (2007).
   PubMed Web of Science ®Google Scholar
• Corripio I , FerreiraA, PortellaMJ et al. The role of striatal dopamine D2 receptors in the occurrence of extrapyramidal side effects: iodine-123-iodobenzamide single photon emission computed tomography study. Psychiatry Res. 201 , 73–77 (2012).
   PubMed Web of Science ®Google Scholar
• Simpson GM , AngusJW. A rating scale for extra-pyramidal side effects. Acta Psychiatr. Scand. Suppl.212 , 11–19 (1970).
   PubMedGoogle Scholar
• Barnes TR . A rating scale for drug-induced akathisia. Br. J. Psychiatry154 , 672–676 (1989).
   PubMed Web of Science ®Google Scholar
• Middelkoop HA , van Dam EM, Smilde-van den Doel DA, van Dijk G. 45-hour continuous quintuple-site actimetry: relations between trunk and limb movements and effects of circadian sleep-wake rhythmicity. Psychophysiology34 , 199–203 (1997).
   PubMed Web of Science ®Google Scholar
• Ventura J , LukoffD, NuechterleinKH. Appendix 1: Brief Psychiatric Rating Scale Expanded Version (4.0) scales, anchor points, and administration manual. Int. J. Meth. Psychiatr. Res.3 , 227–243 (1993).
   Google Scholar
• Andreasen NC . Modified Scale for the Assessment of Negative Symptoms (SANS). University of Iowa Press, IA, USA (1984).
   Google Scholar
• Jaeger J , BitterI, CzoborP, VolavkaJ. The measurement of subjective experience in schizophrenia: the Subjective Deficit Syndrome Scale. Compr. Psychiatry31 , 216–226 (1990).
   PubMed Web of Science ®Google Scholar
• Bond AJ , JamesDC, LaderMH. Sedative effects on physiological and psychological measures in anxious patients. Psychol. Med.4 , 374–380 (1974).
   PubMed Web of Science ®Google Scholar
• Xiang Q , ZhaoX, ZhouY, DuanJL, CuiYM. Effect of CYP2D6, CYP3A5, and MDR1 genetic polymorphisms on the pharmacokinetics of risperidone and its active moiety. J. Clin. Pharmacol.50 , 659–666 (2010).
   PubMed Web of Science ®Google Scholar
• Jovanović N , BožinaN, LovrićM, MedvedV, JakovljevićM, PelešAM. The role of CYP2D6 and ABCB1 pharmacogenetics in drug-naïve patients with first-episode schizophrenia treated with risperidone. Eur. J. Clin. Pharmacol.66 , 1109–1117 (2010).
   PubMed Web of Science ®Google Scholar
• Scordo MG , SpinaE, FacciolàG, AvenosoA, JohanssonI, DahlML. Cytochrome P450 2D6 genotype and steady state plasma levels of risperidone and 9-hydroxyrisperidone. Psychopharmacology (Berl.)147 , 300–305 (1999).
   PubMed Web of Science ®Google Scholar
• Ono S , MiharaK, SuzukiA et al. Significant pharmacokinetic interaction between risperidone and carbamazepine: its relationship with CYP2D6 genotypes. Psychopharmacology (Berl.) 162 , 50–54 (2002).
   PubMed Web of Science ®Google Scholar
• Mihara K , KondoT, Yasui-FurukoriN et al. Effects of various CYP2D6 genotypes on the steady-state plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, in Japanese patients with schizophrenia. Ther. Drug Monit. 25 , 287–293 (2003).
   PubMed Web of Science ®Google Scholar
• Riedel M , SchwarzMJ, StrassnigM et al. Risperidone plasma levels, clinical response and side-effects. Eur. Arch. Psychiatry Clin. Neurosci. 255 , 261–268 (2005).
   PubMed Web of Science ®Google Scholar
• Vermeulen A , PiotrovskyV, LudwigEA. Population pharmacokinetics of risperidone and 9-hydroxyrisperidone in patients with acute episodes associated with bipolar I disorder. J. Pharmacokinet. Pharmacodyn.34 , 183–206 (2007).
   PubMed Web of Science ®Google Scholar
• Wang L , YuL, ZhangAP et al. Serum prolactin levels, plasma risperidone levels, polymorphism of cytochrome P450 2D6 and clinical response in patients with schizophrenia. J. Psychopharmacol. 21 , 837–842 (2007).
   PubMed Web of Science ®Google Scholar
• Novalbos J , López-RodríguezR, RománM, Gallego-SandínS, OchoaD, Abad-SantosF. Effects of CYP2D6 genotype on the pharmacokinetics, pharmacodynamics, and safety of risperidone in healthy volunteers. J. Clin. Psychopharmacol.30 , 504–511 (2010).
   PubMed Web of Science ®Google Scholar
• Walther S , HornH, KoschorkeP, MüllerTJ, StrikW. Increased motor activity in cycloid psychosis compared with schizophrenia. World J. Biol. Psychiatry10 , 746–751 (2009).
   PubMed Web of Science ®Google Scholar
• Kiang M , DaskalakisZJ, ChristensenBK, RemingtonG, KapurS. Actigraphic measurement of the effects of single-dose haloperidol and olanzapine on spontaneous motor activity in normal subjects. J. Psychiatry Neurosci.28 , 293–299 (2003).
   PubMed Web of Science ®Google Scholar
• Wang JS , RuanY, TaylorRM, DonovanJL, MarkowitzJS, DeVaneCL. The brain entry of risperidone and 9-hydroxyrisperidone is greatly limited by P-glycoprotein. Int. J. Neuropsychopharmacol.7 , 415–419 (2004).
   PubMed Web of Science ®Google Scholar

▪ Website

• APSEP clinical trial. http://clinicaltrials.gov/ct2/show/NCT01259973
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