Your Profile Summary & GeneSight Findings
Your profile summary: Partial response to dopaminergic meds (Vyvanse, Wellbutrin). Minimal serotonergic response. ADHD evaluation pending. GeneSight (2017) reveals four findings that explain most of your medication history:
① CYP2D6 Poor Metabolizer (*5/*41) — The biggest finding. CYP2D6 breaks down a large portion of psychiatric drugs. You have one copy with zero activity (*5, a gene deletion) and one with reduced activity (*41). Most CYP2D6-metabolized medications accumulated to higher-than-intended blood levels — causing side effects, unpredictable responses, or paradoxical effects. Prozac, Remeron, Effexor, Cymbalta, Abilify, and more were all affected. (Note: Wellbutrin strongly inhibits CYP2D6, compounding the issue, but is not primarily metabolized by it). You were likely at supratherapeutic levels without knowing it.
② SLC6A4 L/S (Intermediate) — You carry the short allele of the serotonin transporter gene, reducing serotonin transporter expression. GeneSight explicitly flags "decreased likelihood of response to SSRIs." This is genetic — not a dosing issue — explaining why Prozac, Zoloft, Lexapro, Effexor, Cymbalta, and others underperformed.
③ HTR2A G/G (Increased Sensitivity) — Homozygous variant for the serotonin 2A receptor. Associated with increased adverse reactions to SSRIs at the receptor level. Compounds SLC6A4: SSRIs were less likely to work and more likely to cause side effects simultaneously.
④ HLA-A*3101 Present — Genetic marker for higher risk of serious hypersensitivity reactions (SJS, TEN, DRESS) specifically with carbamazepine and oxcarbazepine (CPIC-actionable). AUDIT CORRECTION: CPIC guidelines do NOT extend this marker to lamotrigine — studies examining HLA-A*3101 and lamotrigine SJS report non-significant findings. HLA-B*1502 is absent.
Bottom line: Your medication history wasn't bad luck or inadequate trials. Your genetics stacked the deck against most conventional approaches — making non-serotonergic, non-CYP2D6-metabolized options and non-drug interventions the most rational next steps.