Major depressive disorder (MDD) is a prevalent and debilitating condition, affecting one in six individuals globally. Despite the key role of antidepressants in managing MDD, only ∼35% of patients achieve remission after initial treatment, and many develop treatment-resistant depression. Identifying factors associated with antidepressant outcomes could enhance clinical management and patient care. Utilising new data on self-reported antidepressant outcomes in the UK Biobank, we investigated the sociodemographic, clinical, and genetic predictors of response. In the UK Biobank, Mental Health Questionnaire 2, participants were asked if specific antidepressants had "helped you to feel better" with responses yes/no/other. We tested for associations between self-reported antidepressant response (yes/no) and sociodemographic, clinical, and genetic predictors, including polygenic scores (PGS). We analysed four selective serotonin reuptake inhibitors (SSRI) (N = 18,746), specifically citalopram (N = 8,043), fluoxetine (N = 8,161), paroxetine (N = 2,199) and sertraline (N = 5,605). Logistic regression analyses for risk factors were adjusted for age, sex, and six principal components. We used PGS analysis to evaluate whether genetic likelihood for depression, schizophrenia, bipolar, autism, ADHD, and antidepressant response (remission and percentage improvement), predicted self-reported antidepressant outcome. Across SSRIs, 71%-77% of participants responded positively ('yes') on antidepressant response. Sociodemographic and clinical factors were associated with self-reported antidepressant response, with consistent results across drugs. Lower income (logOR = 0.300, SE = 0.06, p = 4.22 × 10-07), being male (logOR = 0.225, SE = 0.04, p = 8.92 × 10-11), and self-medication with drugs and alcohol (logOR = 0.461, SE = 0.05, p = 2.23 × 10-20) were associated with negative antidepressant outcome responses. A worst episode lasting more than two years (logOR = 0.473, SE = 0.14, p = 4.57 × 10-04), and no brightening of mood in response to positive events during worst episode of depression (logOR = 0.340, SE = 0.66, p =2.57 × 10-06) were also associated with a negative antidepressant outcome. PGS for depression (p = 2.45 × 10-05), ADHD (p = 3.76 × 10-04), autism (p = 5.15 × 10-03), and schizophrenia (p = 1.16 × 10-03) were associated with negative self-reported antidepressant outcome (effect sizes 0.05-0.08 per s.d. of PGS). PGS for non-remission and percentage improvement were negatively associated but not significant, likely reflecting a lack of power in the discovery GWAS. Self-reported antidepressant response outcome in UK Biobank was influenced by sociodemographic, clinical characteristics and common genetic variation, similar to clinical response measures, despite the higher frequency of positive response outcomes. Further analyses using electronic health records are underway to explore the relationship between patient self-response and clinical measures. Nothing to disclose. [ABSTRACT FROM AUTHOR]