Is Amitriptyline and Chlordiazepoxide affected by genetics?
Partially. 1 of 2 ingredients has pharmacogenetic evidence.
Amitriptyline and chlordiazepoxide contains 2 active ingredients, and 1 of them has published pharmacogenetic guidelines. The relevant genes are CYP2C19, CYP2D6. Your genotype can change how that ingredient behaves in your body, while the other ingredients aren't affected by genetics in any clinically established way. 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 chlordiazepoxide, it's worth talking over with your prescriber or pharmacist. How we handle combination products.
What's in Amitriptyline and chlordiazepoxide
Amitriptyline Affected by CYP2C19, CYP2D6
Affected by CYP2C19, CYP2D6. Guidance from CPIC, strong evidence.
Read the full amitriptyline genetics guideChlordiazepoxide No known pharmacogenetics
No strong published pharmacogenetic guideline currently applies to chlordiazepoxide.
Considering GeneSight for Amitriptyline and chlordiazepoxide?
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.
See the comparisonAmitriptyline 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
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 CYP2C19CYP2D6 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 CYP2D6Browse the full drug class: Tricyclic antidepressants.
Related medications
Find out how your genetics affect Amitriptyline and chlordiazepoxide
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.