Induction interactions. Alternatively, there is an increased rate of drug breakdown and resulting decrease in effect when drugs that induce the activity of metabolizing enzymes are used with medications that are substrates of the same enzyme. Carbamazepine is commonly involved in this type of drug interaction because it is a strong inducer of CYP 1A2, 2B6, 2C19, 2C9, and 3A4, and the p-glycoprotein drug efflux pump.9 As a result of this rampant induction, carbamazepine can decrease the serum concentration of oral contraceptives below a reliably effective level. Therefore, it is recommended that women of childbearing potential use other contraceptive methods, such as a progestin implant or an intrauterine device.10
In addition, the polycyclic aromatic hydrocarbons found in cigarettes induce activity of CYP1A2. Patients who smoke and use medications metabolized by this enzyme, such as clozapine and olanzapine, may need a higher dosage.
Drug elimination interactions
The last drug−drug interaction discussed here returns the discussion to Mr. T and involves drug elimination.2 The NSAIDs Mr. T was using for pain likely caused decreased renal excretion of lithium. Because lithium is primarily excreted through the kidneys, Mr. T’s NSAID use, possibly in combination with dehydration caused by gastrointestinal distress, resulted in lithium toxicity. This class of analgesics should be avoided or used cautiously in patients taking lithium.
Clinical applications
The relatively common drug−drug interactions discussed here are just a fraction of the potential interactions mental health practitioners see on a daily basis. Understanding the basics of PD and PK interactions in the setting of patient-specific factors can help to clarify the information found in drug−drug interaction databases, such as Micromedex, Lexicomp, Facts and Comparisons, and Epocrates. Table 2 lists additional insights into drug interactions.
Related Resources
• CredibleMeds. Online resource on QT prolonging drugs. http://crediblemeds.org.
• Madhusoodanan S, Velama U, Parmar J, et al. A current review of cytochrome P450 interactions of psychotropic drugs. Ann Clin Psychiatry. 2014;26(2):120-138.
Drug Brand Names
Benztropine • Cogentin Olanzapine • Zyprexa
Bupropion • Wellbutrin Oxycodone • Oxycontin
Carbamazepine • Tegretol Paroxetine • Paxil
Clozapine • Clozaril Quetiapine • Seroquel
Diphenhydramine • Benadryl Sertraline • Zoloft
Duloxetine • Cymbalta Tamoxifen • Soltamox
Fluoxetine • Prozac Trazodone • Desyrel
Lithium • Eskalith, Lithobid Valproate • Divalproex
Haloperidol • Haldol Ziprasidone • Geodon
Hydrocodone • Vicodin
Disclosure
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.