Use of selective serotonin reuptake inhibitors guided by pharmacogenetic testing may improve treatment response in depression

1. Genotype-guided prescribing of selective serotonin reuptake inhibitors (SSRIs) may improve treatment response in children and adults with depression.

Evidence Rating Level: 1 (Excellent)

Although SSRIs are the most prescribed pharmacotherapy for depression, discontinuation rates remain high, with some studies reporting up to 50% discontinuation due to ineffectiveness or adverse effects. Pharmacogenetic testing may provide individualized therapy by assessing CYP2D6 and CYP2C19 variation. This randomized clinical trial included patients 8 years or older with at least 3 months of depressive symptoms. The authors used Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines to interpret CYP activity, defining an actionable pharmacogenomic phenotype as one for which CPIC guidelines recommend alternative medication selection or dose adjustment. 1460 total patients were randomized to receive either genotype-guided treatment (n = 727) or usual care (n = 733). 341 patients (48 patients aged 8-17 years, mean [SD] age, 14.5 [1.6] years; 293 patients aged 18+ years, mean [SD] age, 41.0 [16.3] years; 72.7% female) had actionable pharmacogenic phenotypes in the usual care group. 351 patients (49 patients aged 8-17 years, mean [SD] age, 14.4 [1.7] years; 302 patients aged 18+ years, mean [SD] age, 40.2 [16.1] years; 75.8% female) had actionable pharmacogenic phenotypes in the genotype-guided group. At 3 months, there were no significant differences in change in Patient-Reported Outcomes Measurement Information System (PROMIS) depression T scores between the genotype-guided and usual-care groups (mean [SD] change, –4.3 [8.4] vs –4.0 [8.1]; P = .68). There were no significant differences in Patient Health Questionnaire-8 score change (mean [SD] change, –3.3 [5.2] vs –2.7 [4.8]; P = .13) or medication adverse effect burden. However, at 6 months, the intervention group had significantly higher PROMIS depression T-score remission rates, defined as score ≤16 (153 of 317 patients [48.3%] vs 122 of 310 patients [39.4%]; P = .02).

Click here to read the study in JAMA Network Open

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