GeneSight & Pharmacogenomics

How to Read Your GeneSight Report

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

A GeneSight report sorts more than 60 psychiatric medications into three columns, “Use as Directed,” “Moderate Gene-Drug Interaction” and “Significant Gene-Drug Interaction,” and then shows the genes behind each placement. The columns are predictions about how your genes may change a drug’s levels or action. They are not a ranking of which drug will work. The most useful habit is to read the small numbered notes beside each medication, then the gene pages that explain your metabolizer types. This guide walks through the report the way you might at your results visit.

The layout, page by page

GeneSight publishes a sample of its Psychotropic report (version 4.3, 15 pages). Yours may list slightly different medications, because the company revises the report over time, but the structure is usually the same:

1. Medication pages, grouped by class. Antidepressants; anxiety and sleep medications; antipsychotics; medications for tardive dyskinesia and mood stabilizers; and ADHD stimulants and non-stimulants. Each page has the three columns, and some have a box for medications the company cannot categorize.
2. Smoker and non-smoker versions. Several classes appear twice. The report defines smoking as daily inhalation of burning plant material, cigarettes or marijuana, and it excludes vaping. Read the version that matches your life, and tell your prescriber if that changes.
3. Pharmacodynamic genes. Genes tied to how a drug acts on its target, such as the serotonin transporter (SLC6A4) and a serotonin receptor (HTR2A), plus two HLA markers linked to serious skin reactions with certain mood stabilizers.
4. Pharmacokinetic genes. Your genotype and predicted metabolizer type for enzymes that clear drugs, including CYP2D6, CYP2C19, CYP2C9, CYP2B6, CYP3A4 and CYP1A2.
5. Additional genotypes. Results shown for information only, such as COMT, which the report says does not meet its criteria for categorizing medications.
6. The gene-drug interaction chart. A grid that shows which gene drove each placement, with an asterisk where the FDA or CPIC recognizes that interaction.
7. Test information. The variants tested, the laboratory, and the limitations, in small print worth reading once.

The three columns, and what they actually signal

The company’s own description is short: the report classifies over 60 mental health medications into three categories. In practice, it helps to keep two lists in your head for each column, what the placement suggests and what it does not.

GeneSight is plain about the limits. Its website says the results do not provide information on disease diagnosis, medication allergies, drug-drug interactions, or which medications will work best. Every page of the sample report also carries the line “Medications should not be changed based solely on the test results.”

Read the small numbers before the columns

Next to many medications sits one or more small numbers. These “clinical considerations” are the most informative part of the report, because they give the reason for the placement. In the sample report they read:

• 1: serum level may be too high; lower doses may be required.
• 2: serum level may be too low; higher doses may be required.
• 3: difficult to predict dose adjustments, because of conflicting variations in metabolism.
• 4: genotype may affect the drug’s mechanism of action and moderately reduce efficacy.
• 6: use of this drug may increase the risk of side effects.
• 7: smoking status changes the result for this medication.
• 8: the FDA label identifies a potential gene-drug interaction.

Two medications in the same column can be there for opposite reasons. One may be flagged because levels could run high, which points toward a gentler start and closer watching. Another may be flagged because levels could run low, which can explain a drug that “did nothing.” A note 4 is a different kind of flag again, based on a pharmacodynamic gene with weaker evidence. Asking “which number, and why?” for each drug you care about turns the report from a traffic light into an explanation.

Note 8 is the one with the firmest footing, since it points to the drug’s FDA labeling. For what that labeling and the expert guidelines do and do not say, see what FDA and CPIC guidance says about pharmacogenomic testing.

The gene pages: genotype first, then phenotype

Each enzyme gene shows two results. The genotype is written in “star” shorthand, such as *1/*2, one entry for each of your two copies. The phenotype is the lab’s prediction of how active the enzyme is, using words like poor, intermediate, normal, rapid or ultrarapid metabolizer. For a plain-language walk through those five words, see CYP2D6 and CYP2C19 metabolizer types explained.

One wording quirk confuses people. The sample report labels a normal result “Extensive (Normal) Metabolizer.” The Clinical Pharmacogenetics Implementation Consortium (CPIC), which standardizes these terms, retired “extensive” in favor of “normal” because clinicians found it misleading. The two words mean the same thing: an enzyme working at the expected rate.

Treat the pharmacodynamic genes with more caution. CPIC’s 2023 antidepressant guideline reviewed SLC6A4 and HTR2A and made no prescribing recommendations, concluding that the evidence is “mixed and insufficient to support clinical utility.” COMT appears in a separate informational section of the report, and MTHFR is a separate GeneSight test. Our overview of genetic testing in psychiatry covers the background on those genes.

Why a medication in the “significant” column may still be used

Placement predicts how your genes may affect a drug. It does not weigh everything else a prescriber has to weigh. Common, legitimate reasons to use a flagged medication anyway:

• It has helped you before. Your own history on a drug is stronger evidence than a prediction about it.
• The issue is levels, and levels can be managed. For some antidepressants, CPIC’s options for poor metabolizers include a lower starting dose and slower increases, as an alternative to switching drugs.
• The alternatives have their own costs. A different drug may bring side effects you have already had, interactions with your other prescriptions, or concerns in pregnancy.
• The flag rests on weaker evidence. A note 4 placement comes from a pharmacodynamic gene, where the science is less settled than for drug-clearing enzymes.

The reverse happens too. A prescriber may pass over a “Use as Directed” medication because of your history, a family member’s bad reaction, or a clash with something else you take.

Why a “Use as Directed” medication can still fail

That column means no gene-drug interaction was found among the genes tested. It cannot account for whether the working diagnosis is right, whether a trial lasted long enough at an adequate dose, missed doses, alcohol, poor sleep, a thyroid problem, or the many reasons people respond differently that no current test measures. It also cannot see the medications you take alongside it, which can change enzyme activity enough to make your genetic result misleading; phenoconversion explains how.

The fine print adds technical limits. The report says your actual genotype may differ from what is reported because of untested variants and technical limitations, and that transplants, such as bone marrow or liver, may affect results. It also states that the test has not been cleared or approved by the FDA; it is a laboratory-developed test. None of that makes the report useless, but it is one more reason it sits beside your history rather than above it. For other reasons a well-chosen drug disappoints, see why antidepressants fail.

Questions to bring to your results visit

• Which of the medications I have already tried appear on the report, and does their placement match what happened to me?
• For each drug in the middle or right column that we might use: is the note about levels, side effects or mechanism?
• What are my CYP2D6 and CYP2C19 types, and do any of my non-psychiatric medicines rely on those enzymes?
• Does anything I take now, or my smoking status, change how we should read this?
• Should my pharmacist and primary care clinician have a copy?

At Willow & Stone, Dr. Stacey Forbes reviews results with you by telehealth or in person, alongside your history, symptoms, other medications and labs. The result is one data point; it never chooses a medication on its own. If you have not been tested yet, what getting a GeneSight test involves covers the swab and the wait, and our main GeneSight testing page explains how testing fits into care here. Until the results visit, keep taking your medications as prescribed.

Common Questions

Sources & Further Reading

• GeneSight — Psychotropic sample report (version 4.3)
• GeneSight — what the test does and does not report
• CPIC guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4 and HTR2A and antidepressants (Bousman et al., 2023)
• Caudle et al., Standardizing terms for clinical pharmacogenetic test results (Genet Med, 2017)
• FDA — Table of Pharmacogenetic Associations

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.