Contains amitriptyline and perphenazineStrong evidence

Is Amitriptyline and Perphenazine affected by genetics?

Yes. All 2 active ingredients have pharmacogenetic evidence.

Genes CYP2C19 CYP2D6

Amitriptyline and perphenazine is affected by pharmacogenetics through the CYP2C19 and CYP2D6 genes. Your genotype for these genes can change how well Amitriptyline and perphenazine works for you or how well you tolerate it. The strongest evidence level on this page is Strong, from the published guidelines shown below.

Pharmacogenetic guidelines are written for one ingredient at a time, so the guidance below is for each ingredient on its own. What your genes mean for a combination product is less clear, because the dose and the other ingredients can change things. If you take Amitriptyline and perphenazine, it's worth talking over with your prescriber or pharmacist. How we handle combination products.

What's in Amitriptyline and perphenazine

Amitriptyline Affected by CYP2C19, CYP2D6

Affected by CYP2C19, CYP2D6. Guidance from CPIC, strong evidence.

Read the full amitriptyline genetics guide

Perphenazine Affected by CYP2D6

Affected by CYP2D6. Guidance from FDA, moderate evidence.

Read the full perphenazine genetics guide

Considering GeneSight for Amitriptyline and perphenazine?

Gene2Rx covers this medication using the same CPIC and FDA guidelines GeneSight uses, costs $35 with the Psychiatric Report or $50 with the Full Report instead of several hundred, and works with your existing 23andMe data. Already have a GeneSight report? Use your GeneSight results.

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Amitriptyline phenotype recommendations

Published guidance from CPIC on how amitriptyline should be dosed or substituted based on your CYP2D6, CYP2C19 phenotype.

Phenotype	What it means	Recommendation	Evidence
Ultrarapid MetabolizerCYP2D6	Your body breaks down this drug very fast, so it may not work well for you. A different drug is often suggested.	CPIC Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments.	Strong
Normal MetabolizerCYP2D6	You are not predicted to have an atypical response to amitriptyline.	CPIC Initiate therapy with recommended starting dose.	Strong
Intermediate MetabolizerCYP2D6	Your body breaks down amitriptyline somewhat more slowly than normal, which may lead to higher drug levels and an increased chance of side effects. A lower starting dose may be recommended.	CPIC Consider 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	Moderate
Poor MetabolizerCYP2D6	Your body breaks down this drug much more slowly, so it builds up and side effects are more likely. A different drug is often suggested.	CPIC Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider 50% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	Strong
IndeterminateCYP2D6	The impact of your genotype on response to this drug is unknown	CPIC Initiate therapy with recommended starting dose.	Not rated
Not availableCYP2D6	The impact of your genotype on response to this drug is unknown	CPIC Initiate therapy with recommended starting dose.	Not rated
Ultrarapid MetabolizerCYP2C19	Your body processes this drug faster than usual, so it may not work as well. A different antidepressant is often suggested.	CPIC Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Rapid MetabolizerCYP2C19	Your body processes this drug faster than usual, so it may not work as well. A different antidepressant is often suggested.	CPIC Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Normal MetabolizerCYP2C19	Your body processes amitriptyline at a normal rate through the CYP2C19 pathway. You are not expected to have an unusual response based on this gene.	CPIC Initiate therapy with recommended starting dose.	Strong
Intermediate MetabolizerCYP2C19	Your body breaks down this drug a little more slowly. The usual starting dose should still work.	CPIC Initiate therapy with recommended starting dose.	Strong
Poor MetabolizerCYP2C19	Your body breaks down this drug much more slowly, which can change how well it works. A different antidepressant, or a lower dose, is often suggested.	CPIC Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	Moderate
Likely Intermediate MetabolizerCYP2C19	Your body likely breaks down this drug a little more slowly. The usual starting dose should still work.	CPIC Initiate therapy with recommended starting dose.	Strong
Likely Poor MetabolizerCYP2C19	Your body likely breaks down this drug much more slowly, which can change how well it works. A different antidepressant, or a lower dose, is often suggested.	CPIC Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	Moderate
IndeterminateCYP2C19	The impact of your genotype on response to this drug is unknown	CPIC Initiate therapy with recommended starting dose.	Not rated
Not availableCYP2C19	The impact of your genotype on response to this drug is unknown	CPIC Initiate therapy with recommended starting dose.	Not rated

Source: CPIC

Perphenazine phenotype recommendations

Published guidance from FDA on how perphenazine should be dosed or substituted based on your CYP2D6 phenotype.

Phenotype	What it means	Recommendation	Evidence
Ultrarapid MetabolizerCYP2D6	Your body processes perphenazine faster than most people, but there is no specific FDA guidance for your genotype. The standard dose is typically used.	FDA Initiate therapy with recommended starting dose.	Not rated
Normal MetabolizerCYP2D6	Your body processes perphenazine at a normal rate. The standard dose should work as expected.	FDA Initiate therapy with recommended starting dose.	Not rated
Intermediate MetabolizerCYP2D6	Your body processes this drug a bit slower than average. The FDA gives no dose change for your result, so the usual dose is used.	FDA Initiate therapy with recommended starting dose.	Not rated
Poor MetabolizerCYP2D6	Your body breaks down perphenazine much more slowly than normal, causing the drug to build up in your system. This increases your risk of side effects.	FDA No specific dosing change in the FDA table. Refer to FDA labeling.	Moderate
IndeterminateCYP2D6	The impact of your genotype on response to this drug is unknown	FDA Initiate therapy with recommended starting dose.	Not rated
Not availableCYP2D6	The impact of your genotype on response to this drug is unknown	FDA Initiate therapy with recommended starting dose.	Not rated

Source: FDA

The genes behind the guidance

CYP2C19 Cytochrome P450 2C19

CYP2C19 handles several SSRIs (citalopram, escitalopram, sertraline), proton pump inhibitors (omeprazole, esomeprazole), and the blood thinner clopidogrel. About 2 percent of people of European ancestry and 13 percent of people of East Asian ancestry are poor metabolizers, and about 30 percent of people of European ancestry are rapid or ultrarapid metabolizers.

For most CYP2C19 drugs, such as the SSRIs and proton pump inhibitors, poor metabolizers build up more drug and rapid or ultrarapid metabolizers clear it faster. Clopidogrel works the other way: it needs CYP2C19 to become active, so poor and intermediate metabolizers get less benefit from it.

See all drugs affected by CYP2C19

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 of people are poor metabolizers (they barely activate CYP2D6), and another 1 to 3 percent are ultrarapid metabolizers (their enzyme is overactive).

The v4 report preserves the activity score used in its interpretation. Some medicines use a combined CYP2D6/CYP2C19 recommendation. CYP2D6 inhibitors can change functional metabolism; a genotype alone does not capture that effect.

See all drugs affected by CYP2D6

Browse the full drug classes: Tricyclic antidepressants, Antipsychotics.

Related medications

Find out how your genetics affect Amitriptyline and perphenazine

This page describes the general pharmacogenetics. A Gene2Rx report analyzes your own DNA to tell you which metabolizer group you fall into, across every medication.

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Informational only, not medical advice. Pharmacogenetic guidance describes population-level patterns; your individual response depends on many factors. Never start, stop, or change a medication without talking to your prescribing clinician.