GeneSight & Pharmacogenomics

Poor, Normal and Ultrarapid Metabolizers: CYP2D6 and CYP2C19 Explained

By Dr. Stacey Forbes, DNP, APRN, PMHNP-BC · Updated October 12, 2026

Your metabolizer type describes how quickly one enzyme is predicted to clear certain drugs, based on the two copies of its gene you inherited. For CYP2D6 and CYP2C19, the two enzymes that matter most for psychiatric medications, the labels run from poor to intermediate, normal, rapid and ultrarapid. A poor metabolizer may build up higher levels of a drug; an ultrarapid metabolizer may clear it before it does much. This guide explains each label, which medications have formal FDA or CPIC guidance, and what a prescriber does differently in principle.

Genotype and phenotype, in plain terms

Every person carries two copies of the CYP2D6 gene and two of CYP2C19, one from each parent. Labs name the versions with “star alleles”: *1 is usually the reference version, and others, such as *4 for CYP2D6 or *17 for CYP2C19, have known effects. Each allele is assigned a function: none, decreased, normal or increased.

Your genotype is the pair you carry, for example CYP2C19 *1/*17. Your predicted phenotype is what that pair is expected to do, for example “rapid metabolizer.” The lab makes that translation using published rules, and the phenotype is the part your prescriber acts on. For CYP2D6, CPIC adds up an “activity score” for the two alleles; extra copies of the gene, called duplications, can push the total high enough to make someone an ultrarapid metabolizer.

The five labels

You may also see “likely intermediate,” “likely poor” or “indeterminate.” Those appear when an allele’s function is uncertain or unknown. “Indeterminate” means the lab could not assign a type, and guidelines make no recommendation for it.

CYP2D6 and psychiatric medications

CPIC’s 2023 guideline notes that CYP2D6 extensively metabolizes fluvoxamine, paroxetine, venlafaxine and vortioxetine. It also handles many antipsychotics and the ADHD medication atomoxetine. The FDA’s Table of Pharmacogenetic Associations sorts gene-drug pairs by how strong the evidence is:

• FDA Section 1 (data support management advice), CYP2D6 poor metabolizers: aripiprazole, brexpiprazole, iloperidone, pimozide, clozapine, vortioxetine, venlafaxine, atomoxetine, amphetamine, and the tardive dyskinesia drugs deutetrabenazine and valbenazine. Thioridazine is contraindicated in poor metabolizers.
• FDA Section 3 (effect on drug levels only; impact on safety or response not established): tricyclics such as amitriptyline and nortriptyline, paroxetine, fluvoxamine and risperidone.

CPIC sometimes goes further than the FDA table. For amitriptyline and nortriptyline, its tricyclic guideline recommends avoiding these drugs in CYP2D6 ultrarapid metabolizers because of potential lack of efficacy, and in poor metabolizers because of potential side effects, with an alternative not cleared by CYP2D6 preferred. For paroxetine, CPIC suggests an alternative for ultrarapid metabolizers and a reduced starting dose for poor metabolizers.

CYP2C19 and psychiatric medications

CPIC describes citalopram, escitalopram and sertraline as extensively metabolized by CYP2C19, which makes this gene the main one for those three common antidepressants.

• Citalopram: in the FDA table’s Section 1. Its label reports that in CYP2C19 poor metabolizers, peak levels rose 68% and overall exposure 107%, and it sets a lower maximum dose for them because higher exposure raises the risk of QT prolongation, a heart rhythm change. CYP2D6 status did not meaningfully change citalopram levels.
• Escitalopram: in the FDA table’s Section 3 for ultrarapid, intermediate and poor metabolizers. CPIC recommends choosing a non-CYP2C19 alternative for ultrarapid metabolizers, and an alternative or a lower start with slower titration for poor metabolizers.
• Sertraline: not in the FDA table. CPIC suggests a lower starting dose and slower titration, or an alternative, for CYP2C19 poor metabolizers, with a moderate strength of recommendation.
• Tricyclics: CPIC also gives CYP2C19 advice for amitriptyline, and the FDA added doxepin to Section 1 for CYP2C19 intermediate and poor metabolizers in its 10 September 2026 update.

What a prescriber does differently, in principle

Formal guidance boils down to a handful of moves. None of them is a reason to change a medication on your own.

One twist matters outside psychiatry. A few drugs are “prodrugs” that the enzyme must activate. For codeine, CYP2D6 ultrarapid metabolizers make more of the active form, and the FDA warns of life-threatening breathing problems; codeine is contraindicated in children under 12. For the heart drug clopidogrel, CYP2C19 intermediate and poor metabolizers make less active drug, and the FDA suggests considering another option. Here the usual logic flips, which is one reason your result belongs in your general medical record too.

What your metabolizer type cannot tell you

CPIC’s tricyclic guideline notes that no diseases or conditions have been convincingly linked to variants in CYP2D6 or CYP2C19. A metabolizer type is not a diagnosis and says nothing about your risk of depression or anxiety. It also does not predict whether a drug will help; it predicts how fast one enzyme will clear it.

Other influences sit on top of the gene. Age, liver and kidney function, pregnancy, and above all other medications can raise or lower enzyme activity. A strong CYP2D6 blocker can make a genetically normal metabolizer behave like a poor one, which is covered in when other medications change your genetic result.

Using your result well

Knowing your types is most useful when the people prescribing for you can see them. Give a copy to your pharmacist and primary care clinician, because CYP2D6 and CYP2C19 also handle pain medicines, heart drugs and acid reducers. Germline results do not change over your lifetime, though the way labs interpret them is updated; see whether pharmacogenomic results last a lifetime. If you are reading these words on your own report, how to read your GeneSight report shows where they appear.

At Willow & Stone, metabolizer types are read alongside what has actually happened on past medications. A poor metabolizer who did well on a drug is a reason for curiosity, not alarm. Dr. Stacey Forbes uses the result to plan a careful start and the right monitoring, as part of GeneSight-informed care, not as a list of forbidden drugs. If you are just starting out, choosing your first antidepressant covers the many other factors that shape the choice, and genetics and psychiatric medication gives the broader picture.

Common Questions

Sources & Further Reading

• CPIC guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4 and HTR2A and antidepressants (Bousman et al., 2023)
• CPIC guideline for CYP2D6 and CYP2C19 and tricyclic antidepressants (Hicks et al., 2017)
• FDA — Table of Pharmacogenetic Associations
• DailyMed — Celexa (citalopram) prescribing information
• Caudle et al., Standardizing terms for clinical pharmacogenetic test results (Genet Med, 2017)

This article is general education, not advice for your situation. Do not start, stop, or change a medication based on a genetic test result without talking to the clinician who prescribes it.