TCAs

Tricyclic antidepressants and pharmacogenetics

Also known as: Tricyclics

7 medications 9 brand products CYP2D6CYP2C19

Why pharmacogenetics matter for tricyclic antidepressants

Tricyclic antidepressants (TCAs) predate SSRIs and remain in use for depression, chronic pain, migraine prevention, and some sleep conditions. Nearly all TCAs are cleared by CYP2D6 and CYP2C19, often in sequence: one enzyme produces an active metabolite, the other clears it. That means TCA dosing is uniquely sensitive to pharmacogenetic variation, and both CPIC and the FDA publish phenotype-based dose guidance.

TCAs have a narrower therapeutic window than SSRIs, so getting the dose right matters more. Poor CYP2D6 metabolizers can reach toxic plasma levels on doses that are routine for normal metabolizers, which is one of the main reasons TCAs have fallen out of first-line use despite generally being as effective as SSRIs for depression.

Key genes in this class

CYP2D6

Cytochrome P450 2D6

CYP2D6 is the most clinically important pharmacogene. It metabolizes around a quarter of all prescription drugs, including many antidepressants, opioids, and stimulants. The gene is unusually variable: roughly 7 percent …

CYP2C19

Cytochrome P450 2C19

CYP2C19 handles several SSRIs (citalopram, escitalopram, sertraline), proton pump inhibitors (omeprazole, esomeprazole), and the blood thinner clopidogrel. About 2 to 5 percent of people of European descent and 15 to …

Medications in this class with pharmacogenetic guidelines

Each link goes to the drug's full pharmacogenetics page with CPIC and FDA phenotype recommendations.

Amitriptyline CYP2C19 / CYP2D6 Clomipramine CYP2C19 / CYP2D6 Desipramine CYP2D6 Doxepin CYP2C19 / CYP2D6 Imipramine CYP2C19 / CYP2D6 Nortriptyline CYP2D6 Trimipramine CYP2C19 / CYP2D6

Brand products in the TCAs class

Combined products and brand names for the medications above. Each links to a pharmacogenetic breakdown.

Which tcas is right for your genetics?

This page covers the pharmacogenetics of tricyclic antidepressants in general. A Gene2Rx report tells you how your personal genotype interacts with every drug on this page.

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Informational only, not medical advice. Pharmacogenetic guidelines describe population-level patterns that inform prescribing decisions. Never start, stop, or change a medication without talking to your prescribing clinician.