Quetiapine and drug interactions: evidence from a routine therapeutic drug monitoring service.
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.


METHODS
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 >or= 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 >or= 70 years (+67%), and carbamaze-pine (-86%). In 18% of the samples, the daily dose exceeded the currently recommended maximum of 800 mg/day.


CONCLUSIONS
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.
Castberg
Ingrid
I
Department of Clinical Pharmacology, St. Olav University Hospital, Norway. ingrid.castberg@stolav.no
Skogvoll
Eirik
E
Spigset
Olav
O
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002220:Carbamazepine / Q000493:pharmacokinetics / Q000627:therapeutic use; D003987:Dibenzothiazepines / Q000378:metabolism* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D016666:Fluvoxamine / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008728:Methotrimeprazine / Q000493:pharmacokinetics / Q000627:therapeutic use; D008875:Middle Aged; D010076:Oxazepam / Q000493:pharmacokinetics / Q000627:therapeutic use; D011618:Psychotic Disorders / Q000188:drug therapy*; D000069348:Quetiapine Fumarate; D014227:Triazines / Q000493:pharmacokinetics / Q000627:therapeutic use
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D014227:Triazines; D000069348:Quetiapine Fumarate; D002220:Carbamazepine; D010076:Oxazepam; D008728:Methotrimeprazine; D016666:Fluvoxamine; D000077213:Lamotrigine