Amitriptyline
Raw research findings for this medication. Mostly single studies, not curated or confirmed robust.
About Amitriptyline
What it is
Amitriptyline is a tricyclic antidepressant (TCA). At higher doses it is used for depression; much more often today it is used at low doses for nerve pain, to prevent migraine and tension headaches, and for some other long-lasting pain. It is sold as Elavil and Endep, among other names.
How genes come into it
CYP2C19 turns amitriptyline into nortriptyline, which is also an antidepressant, and CYP2D6 breaks both down further. People with little or no CYP2D6 activity can build up high levels with more side effects such as drowsiness, dry mouth and effects on the heart rhythm; people with extra CYP2D6 copies clear them quickly. CYP2C19 variants change the balance between the two. CPIC has published a guideline on both genes for amitriptyline, DPWG on CYP2D6, and the US FDA lists an effect on drug levels.
Published guidelines
Clinical guidelines that name a gene for Amitriptyline. They sort people into groups by the gene copies they carry.
CPIC guideline: CYP2C19, CYP2D6. CYP2D6: No Result, activity score 0.0, activity score 0.25, activity score 0.5, activity score 0.75, activity score 1.0, activity score 1.25, activity score 1.5, activity score 1.75, activity score 2.0, activity score 2.25, activity score 2.5, activity score 2.75, activity score 3.0, ≥3.0, ≥3.25, ≥3.5, ≥3.75, activity score 4.0, ≥4.0, ≥5.0, ≥6.0, n/a, xN combinations · CYP2C19: Ultrarapid Metabolizer, Rapid Metabolizer, Normal Metabolizer, Likely Intermediate Metabolizer, Intermediate Metabolizer, Likely Poor Metabolizer, Poor Metabolizer, Indeterminate, No Result. Strong. 2017.
DPWG guideline: CYP2D6. CYP2D6 activity score 0 to 6 or more. 2026.
US FDA: CYP2D6. CYP2D6 activity score 0 to 6 or more. Data that Demonstrate a Potential Impact on Pharmacokinetic Properties Only.
What research found
Every published finding on gene variants and Amitriptyline. Upload your DNA file to see which of these rows apply to you.
Rated evidence (15 rated variants)
PharmGKB weighs all studies of a variant and rates how strong the evidence is, from 1A (strongest) to 4.
CYP2D6 CYP2D6*1, CYP2D6*1xN, CYP2D6*2, CYP2D6*3, CYP2D6*4, CYP2D6*5, CYP2D6*6, CYP2D6*10, CYP2D6*41: Level 1A · replicated. Metabolism/PK: Depressive Disorder, Mental Disorders. 10.
CYP2C19 CYP2C19*1, CYP2C19*2, CYP2C19*3, CYP2C19*17: Level 1A · replicated. Metabolism/PK: Major Depressive Disorder, Mental Disorders. 9.
CYP2D6 CYP2D6*1, CYP2D6*1xN, CYP2D6*2, CYP2D6*3, CYP2D6*4, CYP2D6*5, CYP2D6*6, CYP2D6*10, CYP2D6*41: Level 1A · replicated. Toxicity: Depressive Disorder. 6.
ABCB1 rs2032583: Level 3. Efficacy: Depression, Depressive Disorder, Major Depressive Disorder. 3.
Metabolism (17 findings)
Studies of how quickly the body processes this medication.
CYP2C19 CYP2C19*1, CYP2C19*2: CYP2C19 *1/*2 is associated with increased concentrations of amitriptyline in people with Mental Disorders as compared to CYP2C19 *1/*1.
CYP2C19 CYP2C19*1, CYP2C19*2: CYP2C19 *1/*2 is associated with decreased metabolism of amitriptyline in people with Mental Disorders as compared to CYP2C19 *1/*1.
CYP2C19 CYP2C19*1, CYP2C19*2: CYP2C19 *2/*2 is associated with increased concentrations of amitriptyline in people with Mental Disorders as compared to CYP2C19 *1/*1.
CYP2C19 CYP2C19*1, CYP2C19*2: CYP2C19 *2 is associated with decreased metabolism of amitriptyline in people with Mental Disorders as compared to CYP2C19 *1/*1.
Response (9 findings)
Studies of how well it worked in people carrying a variant.
BDNF rs6265: Genotypes CT + TT is associated with increased clinical benefit to amitriptyline, clomipramine, duloxetine, imipramine, milnacipran or venlafaxine in people with Major Depressive Disorder as compared to genotype CC.
CYP2D6 CYP2D6 poor metabolizer phenotype: CYP2D6 poor metabolizer is associated with decreased response to amitriptyline in people with Phantom limb syndrome as compared to CYP2D6 normal metabolizer.
ABCB1 rs1045642: Allele A is not associated with response to amitriptyline, propranolol or valproic acid in people with Migraine without Aura or Migraine with Aura as compared to allele G.
ABCB1 rs2032583: Genotype GG is not associated with response to amitriptyline, citalopram, escitalopram, nortriptyline, paroxetine, Selective serotonin reuptake inhibitors, sertraline, trimipramine or venlafaxine in people with Bipolar Disorder as compared to genotypes AA + AG.
Dosing (5 findings)
Studies of how much of the drug people needed or tolerated.
CYP2D6 CYP2D6*1, CYP2D6*4: CYP2D6 *4/*4 is associated with decreased dose of amitriptyline, clomipramine, doxepin, imipramine, maprotiline, nortriptyline or Opipramol in people with Depression as compared to CYP2D6 *1/*1.
CYP2D6 rs3892097: Genotype TT is associated with decreased dose of amitriptyline, clomipramine, doxepin, imipramine, maprotiline, nortriptyline or opipramol in people with Depression as compared to genotype CC.
CYP2D6 CYP2D6 poor metabolizer phenotype: CYP2D6 poor metabolizer is not associated with dose of amitriptyline or tramadol in people with Phantom limb syndrome as compared to CYP2D6 normal metabolizer.
CYP2D6 CYP2D6*1, CYP2D6*3, CYP2D6*4, CYP2D6*5, CYP2D6*6: CYP2D6 *3 + *4 + *5 + *6 are not associated with dose of amitriptyline in people with Mental Disorders as compared to CYP2D6 *1/*1.
Side effects (4 findings)
Studies of side effects in people carrying a variant.
CYP2C19 CYP2C19*1, CYP2C19*2: CYP2C19 *2/*2 + *1/*2 are associated with decreased metabolism of amitriptyline in postmortem toxicology cases as compared to CYP2C19 *1/*1.
CYP2D6 CYP2D6*4: CYP2D6 *4/*4 is associated with decreased clearance of amitriptyline in one suicide case.
CYP2D6 CYP2D6 poor metabolizers: CYP2D6 poor metabolizer is not associated with discontinuation of amitriptyline or fluoxetine in people with Depressive Disorder, Major.
CYP2D6 CYP2D6*1, CYP2D6*4: CYP2D6 *4/*4 is not associated with discontinuation of amitriptyline, clomipramine, doxepin, imipramine, maprotiline, nortriptyline and opipramol in people with Depression as compared to CYP2D6 *1/*1.
Other findings (1 finding)
Studies that do not fall into the groups above.
CYP2C19 CYP2C19*1, CYP2C19*17: CYP2C19 *17/*17 is associated with increased discontinuation of amitriptyline or clomipramine in people with Bipolar Disorder as compared to CYP2C19 *1/*1.
Study findings and evidence levels: PharmGKB (CC BY-SA 4.0). Guidelines: CPIC and DPWG, as bundled in PharmCAT. Most studies were done mainly in people of European ancestry.
Related Drugs
More drugs from the same category
Anafranil (TCAs)
Norpramin (TCAs)
Opipramol (TCAs)
Not a prescribing recommendation. This page is educational information about pharmacogenomic research and clinical guidelines - it is not medical or dosing advice, and not a prediction of how any medication will work for you. Never start, stop, or change a medication or dose based on it; talk to your doctor or pharmacist, who can order clinical-grade testing if appropriate.
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Content updated September 2026.
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