title: Investigation of a possible interaction between quetiapine and armodafinil in patients with schizophrenia: an open-label, multiple-dose study.
abstract: The wakefulness-promoting medication armodafinil (R-modafinil) is being studied as an adjunctive treatment for patients with schizophrenia receiving antipsychotic therapy. This open-label study in 37 adults with schizophrenia evaluated whether a drug-drug interaction occurs between armodafinil (a moderate CYP3A4 inducer) and the atypical antipsychotic quetiapine (primarily metabolized by CYP3A4). Patients were required to be on a stable dose of quetiapine ≥300 mg once daily in the evening before enrollment. Steady-state quetiapine pharmacokinetics were determined following daily administration of quetiapine alone in the evening (day 5) and then following concomitant armodafinil administration (titrated to 250 mg) daily in the morning (day 38). In 25 evaluable patients, concomitant armodafinil resulted in a statistically significant decrease in mean AUC(0-24) and C(max) values of quetiapine by 42% and 45%, respectively, versus quetiapine alone. Adverse events occurred more frequently with combination therapy and were consistent with the known profiles of the 2 drugs. No significant changes in mean PANSS negative, positive, and total scores or SANS scores were observed. Although the data do not suggest that the observed decrease in systemic exposure to quetiapine was associated with a change in disease state, patients with schizophrenia should be monitored during combination therapy with quetiapine and armodafinil.
authors: Clinical Pharmacology Department, Cephalon, Inc., 41 Moores Road, Frazer, PA 19355, USA. mdarwish@cephalon.com
authors: Mona
authors: M
authors: Darwish
authors: Mary
authors: M
authors: Bond
authors: Edward T
authors: ET
authors: Hellriegel
authors: James M
authors: JM
authors: Youakim
authors: Ronghua
authors: R
authors: Yang
authors: Philmore
authors: P
authors: Robertson
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D011569:Psychiatric Status Rating Scales; D000069348:Quetiapine Fumarate; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D012565:Schizophrenic Psychology
chemical_list: D014150:Antipsychotic Agents; D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D000077408:Modafinil