Quetiapine and Drug Interactions: Evidence From a Routine Therapeutic Drug Monitoring Service

Ingrid Castberg, M.D.; Eirik Skogvoll, M.D., Ph.D.; and Olav Spigset, M.D., Ph.D.

Objective: The objective of the present study was to investigate the effect of age, gender, and various comedications on the pharmacokinetics of quetiapine in a naturalistic setting.

Method: In total, 2111 serum samples analyzed for quetiapine during the period from June 2001 to December 2004 were included in the study. The samples had been collected for routine therapeutic drug monitoring purposes from 1179 patients treated with quetiapine. A log-linear mixed model was used to identify factors influencing the dose-corrected quetiapine serum concentration, expressed as the quetiapine concentration-to-dose (C/D) ratio. Variables included in the analysis were age, gender, and concomitant treatment with a total of 41 drugs most often used in combination with quetiapine.

Results: Age >= 70 years (p = .001) and comedication with alimemazine (p = .002), fluvoxamine (p = .001), citalopram/escitalopram (p = .041), or clozapine (p < .001) significantly increased the serum concentrations of quetiapine, while age < 18 years (p = .044) and comedication with lamotrigine (p = .024), levomepromazine (p = .011), oxazepam (p < .001), or carbamazepine (p < .001) significantly decreased the serum concentrations. The effects were most pronounced for fluvoxamine (+159%), clozapine (+82%), age >= 70 years (+67%), and carbamazepine (-86%). In 18% of the samples, the daily dose exceeded the currently recommended maximum of 800 mg/day.

Conclusion: Due to the increased serum levels of quetiapine, a lower dose than usual should be considered when quetiapine is administered to elderly patients and to patients comedicated with clozapine or fluvoxamine. As the inducing effect of carbamazepine on quetiapine metabolism is very potent, cotreatment with carbamazepine cannot be recommended. On the basis of our data and pharmacokinetic considerations, the majority of drugs commonly used in psychiatry can safely be given in combination with quetiapine.

(J Clin Psychiatry 2007;68:1540-1545)

Received Nov. 9, 2006; accepted Jan. 18, 2007. From the Departments of Clinical Pharmacology (Drs. Castberg and Spigset), Forensic Psychiatry Brøset (Dr. Castberg), and Anaesthesiology and Intensive Care (Dr. Skogvoll), St. Olav University Hospital; and the Department of Neuroscience (Dr. Castberg), the Unit for Applied Clinical Research, Faculty of Medicine (Dr. Skogvoll), and the Department of Laboratory Medicine, Children's and Women's Health (Dr. Spigset), Norwegian University of Science and Technology, Trondheim, Norway.

The authors report no financial affiliations or other relationships relevant to the subject of this article.

Corresponding author and reprints: Ingrid Castberg, Department of Forensic Psychiatry Brøset, P.O. Box 1803 Lade, NO-7440 Trondheim, Norway (e-mail: ingrid.castberg@stolav.no).