Lecture 2
Learn How to Read a GeneSight Report
GeneSight Report
🧬 How to Read a GeneSight® Report: Teaching Guide
🔹 SECTION 1: What Is GeneSight and Why It Matters
Purpose: A pharmacogenomic test that helps personalize psychotropic medication choices by examining how genes affect metabolism and response.
Focus: Guides decisions on which meds to avoid, which may require dose adjustments, and which are likely to work best.
🧑🏫 “Think of it as a GPS for psychiatric prescribing—especially when past treatment failed.”
🔹 SECTION 2: Understanding the Traffic Light System
Each medication falls into one of three categories:
ColorMeaningAction🟢 GreenUse as DirectedStandard starting dose, routine monitoring.🟡 YellowModerate InteractionConsider dose change or monitoring side effects closely.🔴 RedSignificant InteractionUse caution or avoid unless there's no alternative.
🧑🏫 “This is your visual cue for how genetically compatible a drug is for the patient.”
🔹 SECTION 3: Clinical Considerations Tags
Look for small numbers next to meds:
1: May lead to high serum levels – lower dose may be needed.
2: May lead to low serum levels – higher dose may be needed.
4: Decreased medication efficacy.
6: Higher risk of side effects.
7: Smoking status changes metabolism.
10: No specific gene marker, but still clinically useful.
🧑🏫 “Tag numbers are your clinical context — they tell you why a drug ended up in red or yellow.”
🔹 SECTION 4: Smoking Status Matters
CYP1A2 enzyme is inducible by smoking.
A smoker with an “A” allele may rapidly metabolize drugs like clozapine, olanzapine, or duloxetine, lowering their effectiveness.
🧑🏫 “Always check the smoking box first—this can change the interpretation completely!”
🔹 SECTION 5: Pharmacokinetics (PK) – How the Body Handles the Drug
Each gene is linked to how drugs are metabolized:
GeneRoleCYP2D6 / CYP2C19 / CYP3A4Metabolize SSRIs, antipsychotics, mood stabilizers.UGT1A4 / UGT2B15Metabolize mood stabilizers like lamotrigine.CES1A1Involved in metabolism of stimulants.CYP1A2Affected by smoking, metabolizes antipsychotics & antidepressants.
🧑🏫 “Look for ‘intermediate’ or ‘ultrarapid’ phenotypes — these tell you how drug levels may rise or fall.”
🔹 SECTION 6: Pharmacodynamics (PD) – How the Brain Responds
These genes affect medication response:
GeneInterpretationSLC6A4 (L/S)Short allele = may reduce SSRI response.HTR2ANormal = typical serotonin receptor sensitivity.MTHFR (T/T)Reduced folate metabolism; may need L-methylfolate.COMT (Val/Met)Informational; relates to dopamine and stress resilience.
🧑🏫 “SLC6A4 short variant? SSRIs might not be first-line. MTHFR T/T? Consider folate support.”
🔹 SECTION 7: Clinical Application with Failed Medications
Use the GeneSight report in real-world context:
Match genetic results with past failures.
Avoid repeating ineffective meds.
Consider alternate mechanisms or augmentations.
📌 Example: This patient failed aripiprazole and has an intermediate CYP3A4 metabolism — this could have lowered drug effectiveness.
🔹 SECTION 8: Teaching Tips
✅ Always begin with the clinical picture — use the report to enhance, not replace, your judgment.
✅ Cross-reference failed meds to see if genetics explain why.
✅ Consider using L-methylfolate in patients with MTHFR T/T.
✅ Teach students to differentiate between PK and PD effects.