What do red, yellow, and green results mean in GeneSight (Genetic Sensitivity Testing) testing?

Understanding GeneSight Testing Results: Red, Yellow, and Green Categories

GeneSight testing categorizes psychiatric medications into three color-coded bins—green ("use as directed"), yellow ("use with caution"), and red ("use with increased caution and more frequent monitoring")—based on how your specific genetic variants in CYP450 enzymes (primarily CYP2D6 and CYP2C19) and serotonin-related genes affect medication metabolism and response. 1, 2

How the Color Categories Work

Green Bin: "Use as Directed"

• Medications in the green bin have minimal predicted gene-drug interactions based on your specific genetic profile 2, 3
• These drugs are expected to be metabolized normally by your body's enzyme systems 1
• Certain medications appear in the green bin for most patients (>90% of the time) simply because they don't rely heavily on CYP450 metabolism: desvenlafaxine, levomilnacipran (antidepressants), and asenapine, lurasidone, paliperidone, ziprasidone (antipsychotics) 2
• Patients on green-bin medications showed 28.5% improvement in depressive symptoms in clinical trials 4

Yellow Bin: "Use with Caution"

• Medications in this category have moderate gene-drug interactions that may require dose adjustments or closer monitoring 2, 3
• Your genetic variants suggest these drugs might be metabolized faster or slower than average, potentially affecting efficacy or side effects 1
• Patients on yellow-bin medications showed 32.5% improvement in depressive symptoms, which was significantly better than those on red-bin medications (p=0.002) 4

Red Bin: "Use with Increased Caution and More Frequent Monitoring"

• These medications have significant predicted gene-drug interactions based on your genetic profile 2, 3
• Critical finding: Patients who remained on red-bin medications showed only 0.8-12% improvement in depressive symptoms, far less than those switched to genetically suitable medications (33.1% improvement, p=0.06) 3, 4
• Common red-bin medications for many patients include: citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, paroxetine, sertraline (antidepressants), and chlorpromazine, thioridazine (antipsychotics)—these drugs heavily depend on CYP450 metabolism 2

Clinical Evidence and Limitations

Supporting Evidence

• Meta-analysis of 1,556 patients showed GeneSight-guided care resulted in 10.08% greater symptom improvement (p=0.019), 1.40-fold increased response rate (p<0.001), and 1.49-fold increased remission rate (p=0.001) compared to unguided treatment 5
• The number needed to treat for one additional clinical response was 6.07 patients 4
• GeneSight-guided patients had 2.3-fold increased odds of clinical response compared to treatment-as-usual (p=0.004) 4

Critical Limitations

• The EGAPP Working Group found insufficient evidence that CYP450 genetic testing improves clinical outcomes for depression treatment, with strength of evidence rated as low 1
• The American College of Medical Genetics notes that while genetic testing has high technical accuracy (94-100% analytic sensitivity), the link between genotype and actual clinical response remains complex and inconsistent 1
• A critical analysis revealed that GeneSight results can be predicted simply by knowing which drugs depend on CYP450 metabolism—newer drugs with non-oxidative clearance pathways consistently appear in green bins, while older CYP-dependent drugs appear in red bins 2
• Multiple factors beyond genetics significantly affect drug metabolism, including diet, drug interactions, and individual patient characteristics 1

Practical Clinical Application

When Results May Be Most Useful

• Patients with prior treatment failures or adverse reactions to multiple psychiatric medications 1
• Identifying the 30% of patients with severe gene-drug interactions who benefit most from medication switches 3
• For CYP2D6 poor metabolizers: reduce fluoxetine, paroxetine, and venlafaxine doses by 50% with mandatory therapeutic drug monitoring 1
• For CYP2C19 poor metabolizers: reduce citalopram and escitalopram doses by 50% 1

Common Pitfalls to Avoid

• Do not use GeneSight as a routine screening tool for all patients starting antidepressants—evidence does not support this approach 1
• Do not ignore clinical judgment in favor of genetic results alone—the test provides one piece of information among many factors 1
• Do not assume green-bin medications are automatically the best choice—clinical factors, comorbidities, and patient preferences remain essential 2
• Recognize that approximately 5-8% of Caucasians are CYP2D6 poor metabolizers and 1-7% are ultrarapid metabolizers, affecting how they process many psychiatric medications 1