GeneSight & Pharmacogenomics

When Other Medications Change Your Genetic Result (Phenoconversion)

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

Phenoconversion means your body handles a drug differently from what your genetic result predicts, because something else you take is blocking or speeding up the same enzyme. Fluoxetine, paroxetine and bupropion, for example, are strong blockers of CYP2D6; while you take one, a person with normal CYP2D6 genes can clear certain drugs like a poor metabolizer. Smoking, St. John’s wort and grapefruit work on other enzymes. Your genes stay the same, but the practical answer changes, which is why a pharmacogenomic report always has to be read next to your current medication list.

Your genes predict; your medication list decides

A pharmacogenomic test reads the genes for your drug-clearing enzymes and predicts how active those enzymes should be. CPIC, the consortium that writes gene-drug guidelines, defines phenoconversion as the mismatch between that genetically predicted phenotype and the one actually observed, caused by an inhibitor or inducer of the enzyme. How big the shift is depends on your starting type and on the strength and duration of the other drug.

Inhibitors slow an enzyme down, so drugs it clears build up. Inducers speed an enzyme up, so drugs it clears fall. Neither changes your DNA. When the other drug is stopped, the enzyme drifts back toward its genetic baseline, sometimes quickly and sometimes over weeks.

CPIC also notes that agreed methods for adjusting a predicted phenotype for inhibitors and inducers have not been established. In other words, there is no simple formula; your prescriber has to reason it through. If you are new to the metabolizer labels themselves, start with CYP2D6 and CYP2C19 metabolizer types.

Strong CYP2D6 blockers, several of them psychiatric

The FDA keeps a reference list of drugs that inhibit or induce each enzyme. For CYP2D6, it lists bupropion, fluoxetine, paroxetine, quinidine and terbinafine as strong inhibitors, duloxetine as moderate, and escitalopram, sertraline and fluvoxamine among the weak ones. That means three commonly prescribed psychiatric medications can, on their own, change how CYP2D6 handles everything else you take.

The atomoxetine label shows how large the effect can be. In people who were not genetically poor metabolizers, adding paroxetine raised atomoxetine exposure about 6.5-fold and adding fluoxetine about 6- to 8-fold. Genetic poor metabolizers have roughly 10-fold higher exposure. The label gives the same dosing advice to both groups: people taking a strong CYP2D6 inhibitor and people who are poor metabolizers by genotype.

Two more details are worth knowing. CPIC’s atomoxetine guideline notes that fluoxetine’s effect may last up to two to three months after it is stopped in an average patient, and longer in some people. And paroxetine can partly block its own breakdown, so CPIC says it can shift normal metabolizers toward intermediate or poor metabolism as the dose and steady-state levels rise.

CYP2C19 blockers

The FDA lists fluconazole, fluoxetine, fluvoxamine and ticlopidine as strong CYP2C19 inhibitors. These matter for citalopram, escitalopram and sertraline, which CPIC describes as extensively metabolized by CYP2C19.

The citalopram label makes the parallel explicit. It sets the same lower maximum dose for people taking cimetidine or another CYP2C19 inhibitor as it does for CYP2C19 poor metabolizers, because higher exposure raises the risk of QT prolongation. So a report that says “normal CYP2C19” does not settle the question if a CYP2C19 blocker, such as a course of fluconazole for a yeast infection, has just been added.

Smoking and CYP1A2

Tobacco smoke is listed by the FDA as a moderate CYP1A2 inducer. CYP1A2 clears clozapine and olanzapine, among others. The clozapine label says tobacco smoke can lower clozapine levels, and it advises considering a dose reduction when a CYP1A2 inducer such as tobacco smoke is stopped; its patient information asks whether you plan to stop smoking.

GeneSight builds part of this in. Its report prints separate smoker and non-smoker pages for medications that depend on CYP1A2, defines smoking as daily inhalation of burning plant material including marijuana, and excludes vaping. Its test information adds that marijuana smoking is expected to act on CYP1A2 in a way similar to tobacco. If you quit, cut down or start smoking after you are tested, the other page may now apply.

St. John’s wort, grapefruit and other inducers

Two non-prescription items show up on the FDA list. St. John’s wort is a strong CYP3A inducer, in the same category as carbamazepine, phenytoin and rifampin. Grapefruit juice is a moderate CYP3A inhibitor, and the FDA notes that some preparations can act as strong ones. For CYP2C19, rifampin is the listed strong inducer, with efavirenz, phenytoin and others as moderate.

CYP3A4 is not the headline gene on most psychiatric panels, but it clears many psychiatric drugs, and inducers can lower levels enough that a drug seems to stop working. Our guide to supplement and psychiatric medication interactions covers St. John’s wort and grapefruit in more depth, and cannabis, CBD and psychiatric medication covers CBD.

Putting your genes and your medication list together

No table can capture every combination, and the FDA calls its own list a guide rather than a complete one. The point is the habit: whenever a medication is added or removed, the genetic result gets reread in that light.

What this means for your report and your visit

GeneSight says its results do not provide information on drug-drug interactions. So a placement on your report assumes the enzyme is running at its genetic setting. If you were already taking fluoxetine or bupropion when you swabbed, your report still shows your genes, but your body may currently be handling CYP2D6 drugs very differently. How to read your GeneSight report covers the parts of the report this affects.

• Bring a complete list: prescriptions, over-the-counter drugs, antifungals or antibiotics from the last few months, supplements, and whether you smoke tobacco or cannabis.
• Mention any recent stop of fluoxetine, since its blocking effect can linger for weeks.
• Ask your pharmacist to flag CYP2D6 and CYP2C19 inhibitors whenever a new drug is dispensed.
• Do not stop or swap anything on your own to “fix” a result; abrupt changes carry their own risks.

At Willow & Stone, Dr. Stacey Forbes reviews pharmacogenomic results against everything you actually take, which is often where the most useful finding turns up. That review is part of how GeneSight testing is used here, never a standalone printout.

Common Questions

Sources & Further Reading

• FDA — Drug development and drug interactions: examples of CYP inhibitors and inducers
• CPIC guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4 and HTR2A and antidepressants (Bousman et al., 2023)
• CPIC guideline for CYP2D6 and atomoxetine (Brown et al., 2019)
• DailyMed — Strattera (atomoxetine) prescribing information
• DailyMed — Clozaril (clozapine) prescribing information
• DailyMed — Celexa (citalopram) prescribing information

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.