Amitriptyline and CYP2C19

Haval Norman, Pharm.D. Candidate; Emily Loudermilk, Pharm.D. Candidate.

About the Drug

Amitriptyline (Elavil® and generic products) and other tricyclic antidepressants (TCAs) are used for patients with depression. Low levels of the chemicals norepinephrine and serotonin in the brain are connected to depression symptoms. These include loss of pleasure, loss of interest, and fatigue. Amitriptyline and other TCAs act to increase the levels of these chemicals in the brain. Consequently, these medications will help to resolve symptoms of depression.

About the Gene

The gene of interest is cytochrome P450-2C19 (CYP2C19; pronounced sip two see nineteen). CYP2C19 is involved in creating chemicals that break down amitriptyline. There are a number of different genes present in the population, and they can result in differences in how you break down this medication.

About the Drug-Gene Interaction

There is a relationship between the CYP2C19 gene, CYP2C19 function in an individual and amitriptyline efficacy and side effects. Individuals with high activity in this gene could need a dose increase for the medication to work; however, alternative drug therapy may be considered. Individuals with genes coding for decreased activity may develop higher concentrations of amitriptyline, and therefore a reduction of dosage may be required to prevent increased risk of side effects.

Provider Information

The links below provide access to important articles and information relative to amitriptyline. The links are to external websites and will be checked regularly for consistency.

Sources of Information

DailyMed [Internet]. Bethesda (MD): U.S. National Library of Medicine; c1993-2013. Amitriptyline Hydrochloride; [cited 2013 Dec 1]; [about 3 screens]. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e6d2c80-fbc8- 444e-bdd3- 6a91fe1b95bd/.

Hicks JK, Swen JJ, Thorn CF, Sangkuhl K, Kharasch ED, Ellingrod VL, Skaar TC, Muller DJ, Gaedigk A, Stingl JC. Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clinical Pharmacology & Therapeutics. 2013 May;93(5):402-8.

Jiang ZP, Shu Y, Chen XP, Huang SL, Zhu RH, Wang W, He N, Zhou HH. The role of CYP2C19 in amitriptyline N-demethylation in Chinese subjects. European Journal of Clinical Pharmacology. 2002 May;58(2):109-13.

Moret C, Briley M. The importance of norepinephrine in depression. Neuropsychiatric Disease and Treatment. 2011;7(Suppl 1):9-23.

Nutt DJ. Relationship of neurotransmitters to the symptoms of major depressive disorder. The Journal of Clinical Psychiatry. 2008:69(Suppl E1):4-7.