GeneSight — what his genes say about his meds

Patient: Paul Mederos Sr. (DOB 2/14/1963). Collected 6/8/2026, reported 6/16/2026. Ordered by Ms Ninoska Gaminara, NP-C, GNP-BC. GeneSight Psychotropic Test v5.0 + GeneSight MTHFR. Order #6813739.

Framing. This is Paul's lay reading for the family record. Not clinical advice, not a diagnosis. GeneSight is a decision aid: it predicts how Dad metabolizes psychiatric drugs, it does not tell anyone to start, stop, or change a medication. The report's own line: medications should not be changed based on the test alone. Hand the care team the original PDF; this page is the map to talk over it.

Why it was ordered

Per the medical-necessity page, the ordering clinician was considering a dosage adjustment to currently prescribed medication(s) — specifically Cymbalta (duloxetine) and Desyrel (trazodone), both listed as having failed to work. Diagnoses on file for the order: recurrent severe major depression (F33.2), Tourette's disorder (F95.2), and generalized anxiety disorder (F41.1).

The ordering clinician, Ninoska Gaminara (NP-C, GNP-BC), is not yet in our care-team log — worth confirming whether this is The Recovery Team or the Apollo Beach side, so results route to the right prescriber. GNP-BC = board-certified gerontological NP.

Headline takeaways

1. Duloxetine (the reason for the test): he runs it high, not low. Dad is a CYP2D6 intermediate metabolizer, so duloxetine levels tend to run relatively high for the dose. GeneSight flags it "serum may be too high, lower dose may be required." The genetics argue against simply pushing the dose up — if it failed at 80 mg/day, that points to lowering it (if the problem was side effects) or switching agents (if the problem was lack of response), not escalating.
2. Olanzapine is genetically fine ("use as directed"). No gene-drug red flag on his current antipsychotic at his (non-smoker) status. The metabolic risk from the 2025 labs is still the real watch-item — but that is not a pharmacogenomic problem.
3. Clopidogrel should work (answers an open cardiology question). Dad is a CYP2C19 ultrarapid metabolizer, so he activates clopidogrel (Plavix) fully. He is not the non-responder we flagged as a question — reassuring for his post-Watchman, post-stroke antiplatelet coverage.
4. Some benzos accumulate in him; two don't (a genuinely useful safety flag). He is a UGT2B15 poor metabolizer, so lorazepam (Ativan) and oxazepam clear slowly and build up — extra sedation and fall risk. But alprazolam (Xanax) and clonazepam (Klonopin) are gene-clean: if a benzo is ever clinically needed, those are the safer genetic choices for him.
5. No surprises that block other options. MTHFR is normal (no methylfolate needed on genetic grounds). The SJS/Stevens-Johnson risk genes (HLA-A*3101, HLA-B*1502) are both negative — so carbamazepine / lamotrigine are genetically lower-risk if an anticonvulsant is ever added for kindling.

His metabolizer profile

The pharmacokinetic genes — how fast he clears each drug class:

The pharmacodynamic genes — how his receptors respond:

What it means for his current meds

1. Duloxetine (Cymbalta) 80 mg/day — the core finding

CYP2D6 intermediate means higher exposure per milligram. GeneSight puts it in the moderate column: "serum level may be too high, lower doses may be required." Two ways to read "it failed," and they point opposite directions on dose:

• If it failed on side effects → consistent with it being effectively over-dosed for his metabolism → a lower dose may be the move.
• If it failed on lack of response despite adequate levels → he is already getting plenty of drug, so pushing higher is unlikely to help → favors a switch, not escalation.

If a switch is on the table, the report's gene-favorable antidepressants ("use as directed") are: desvenlafaxine (Pristiq), levomilnacipran (Fetzima), vilazodone (Viibryd), and vortioxetine (Trintellix). Desvenlafaxine is worth a star — it is the active metabolite of venlafaxine and largely bypasses CYP2D6, so it sidesteps exactly his slow pathway while covering the same mood + nerve-pain indication. And given the SLC6A4 short allele (lower SSRI response), an SNRI-class agent fits him better than an SSRI anyway. (Opinion / discussion point for the prescriber, not a recommendation to change anything.)

2. Olanzapine (Zyprexa) 10 mg — green

"Use as directed" at his non-smoker status. No genetic reason to change it. Keep the metabolic monitoring (glucose / A1c / lipids / weight) that the 2025 baseline calls for — that is the live concern with olanzapine, independent of genetics.

3. Benzodiazepines — UGT2B15 poor metabolizer

This is the most actionable safety finding. He clears the UGT2B15-dependent benzos slowly, so they accumulate:

• UGT2B15-driven, accumulate (significant flag): lorazepam (Ativan), oxazepam (Serax) — the two his slow UGT2B15 pathway clears.
• Also in the report's significant column, but a different mechanism: diazepam (Valium) — flagged via CYP2B6 + CYP2C19, not UGT2B15.
• Not flagged by the report: temazepam (Restoril) sits under "no proven genetic markers." It is a UGT2B15 substrate on paper, but GeneSight does not categorize it — so don't read it as a flagged accumulator (it is the closest thing to a gene-neutral sleep benzo here).
• Gene-clean (use as directed): alprazolam (Xanax), clonazepam (Klonopin), chlordiazepoxide, buspirone.

Given the benzo history and the fall-risk concern, this matters: if a benzo is ever indicated again, the gene-preferred choices are the ones he was historically on (Xanax / Klonopin), not Ativan. None of these are currently scheduled — this is for future decisions and as-needed dosing.

4. Clopidogrel (Plavix) — CYP2C19 ultrarapid

Clopidogrel is a prodrug that CYP2C19 has to switch on. As an ultrarapid metabolizer, Dad activates it fully — he is not the non-responder that a CYP2C19 poor metabolizer would be. That is reassuring for his antiplatelet coverage after the Watchman + stroke.

Caveats worth stating plainly: GeneSight is a psychiatric panel and does not issue a clopidogrel recommendation — this is reading his CYP2C19 phenotype across to the cardiology drug. Per CPIC, the implications of ultrarapid status are less certain than poor-metabolizer status, and the higher-bleeding-risk signal in the literature is inconsistent. Bottom line: this answers "is he a clopidogrel non-responder?" (no), and the rest is a conversation for cardiology — not a mandate.

5. Metoprolol — a low-priority footnote (CYP2D6 intermediate)

Also outside GeneSight's panel, but metoprolol is a CYP2D6 substrate, so the same intermediate status nudges his exposure up. CPIC still recommends standard dosing for intermediate metabolizers — the practical note is just to watch for bradycardia / fatigue, made slightly more relevant because duloxetine also inhibits CYP2D6 (gene + drug stacking). His BP running 160+ says he is clearly not over-beta-blocked today, so this is a back-pocket note, not an action.

If the tic regimen gets rebuilt

The neuro visit may add a dedicated tic agent. Genetic notes for that conversation:

• Antipsychotics "use as directed": cariprazine, lumateperone, lurasidone, quetiapine, ziprasidone (plus asenapine, clozapine, haloperidol, olanzapine at non-smoker status).
• Moderate (CYP2D6-driven, dose-aware): aripiprazole, brexpiprazole, risperidone, iloperidone.
• VMAT2 inhibitors for tics / tardive dyskinesia (valbenazine, deutetrabenazine) come up moderate — CYP2D6 intermediate means start-low and titrate.
• TCAs are the red column: amitriptyline, doxepin, imipramine all carry a significant gene-drug interaction (CYP2D6 + CYP2C19) — relevant if a tricyclic is ever floated for nerve pain or sleep.

Questions worth raising with the prescriber

1. Duloxetine: given CYP2D6 intermediate (levels run high), is the plan to lower the dose, or switch? If switching, is desvenlafaxine (Pristiq) — which bypasses CYP2D6 — a fit for the mood + nerve-pain indication?
2. Confirm the ordering clinician. Who is Ninoska Gaminara, NP-C — TRT or Apollo Beach? Make sure results land with whoever owns his psych meds.
3. Benzo safety on the chart: flag UGT2B15 poor metabolizer so any future as-needed benzo defaults to alprazolam / clonazepam over Ativan / oxazepam (the UGT2B15-cleared ones).
4. Share CYP2C19 ultrarapid + CYP2D6 intermediate with cardiology — clopidogrel is covered; metoprolol is a watch-for-bradycardia note, more so alongside duloxetine.
5. For the tic regimen: if a VMAT2 or atypical antipsychotic is added, dose with the CYP2D6 intermediate status in mind (start low).

The bottom line

Nothing here is alarming, and a couple of findings are quietly reassuring (clopidogrel works; olanzapine is genetically fine; no methylfolate gap). The test did its job on the duloxetine question and threw in two bonuses — the clopidogrel answer and the benzo-safety flag — that touch threads already open in his care. It is a conversation map, not a set of orders.

Source of truth: GeneSight Psychotropic + MTHFR report PDF (19 pages). Hand this to the care team, not the summary.