title: Effect of fluoxetine and imipramine on the pharmacokinetics and tolerability of the antipsychotic quetiapine.
abstract: The effects of fluoxetine and imipramine on the pharmacokinetics and nonpsychiatric side effect profile of quetiapine fumarate were investigated in 26 patients with schizophrenia, schizoaffective disorder, or bipolar disorder in a multicenter, two-period, multiple-dose, open-label, randomized trial. Over a 1- to 2-week period, patients were titrated to a 300-mg twice-daily dose of quetiapine. Patients treated for at least 7 days at the target dose entered a combination therapy period, receiving fluoxetine (60 mg daily) or imipramine (75 mg twice daily) for 8 days. Key assessments included pharmacokinetic analysis of quetiapine, the Udvalg for kliniske undersøgelser (UKU) Side Effect Rating Scale, and safety evaluations (e.g., adverse events, electrocardiograms, laboratory tests, and vital signs). Fluoxetine increased the quetiapine area under the plasma concentration time curve during a 12-hour interval (+12%), maximum plasma concentration during the dosing interval (C(ss)(max); +26%), and minimum plasma concentration at the end of the dosing interval (+8%), although it decreased oral clearance (-11%). The change in C(ss)(max) was statistically although not clinically significant. Imipramine did not affect the pharmacokinetics of quetiapine. Overall, scores on the UKU Side Effect Rating Scale improved during combination therapy with either agent, and no statistically significant deterioration was observed for any item. For safety assessments, the only clinically remarkable event was an imipramine-associated complete left bundle branch block in one patient. No unexpected side effects were reported. In conclusion, combination therapy with quetiapine and fluoxetine or imipramine had a minimal effect on quetiapine pharmacokinetics and was well tolerated.
authors.affiliation: Department of Psychiatry and Human Behavior, University of California, Irvine, Medical Center, Orange, USA. sgpotkin@uci.edu
authors.forename: Steven G
authors.initials: SG
authors.lastname: Potkin
authors.forename: Per T
authors.initials: PT
authors.lastname: Thyrum
authors.forename: Gustavo
authors.initials: G
authors.lastname: Alva
authors.forename: Danilo
authors.initials: D
authors.lastname: Carreon
authors.forename: Chiao
authors.initials: C
authors.lastname: Yeh
authors.forename: Amir
authors.initials: A
authors.lastname: Kalali
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Arvanitis
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001714:Bipolar Disorder / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D003987:Dibenzothiazepines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D007099:Imipramine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008875:Middle Aged; D011618:Psychotic Disorders / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D000069348:Quetiapine Fumarate; D012559:Schizophrenia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D005473:Fluoxetine; D000069348:Quetiapine Fumarate; D007099:Imipramine