In major depressive disorder (MDD), only ~35% achieve remission after first-line antidepressant therapy. Using UK Biobank data, we identify sociodemographic, clinical, and genetic predictors of antidepressant response through self-reported outcomes, aiming to inform personalized treatment strategies.

In UK Biobank Mental Health Questionnaire 2, participants with MDD reported whether specific antidepressants helped them. We tested whether retrospective lifetime response to four selective serotonin reuptake inhibitors (SSRIs) (N = 19,516) – citalopram (N = 8335), fluoxetine (N = 8476), paroxetine (N = 2297) and sertraline (N = 5883) – was associated with sociodemographic (e.g. age, gender) and clinical factors (e.g. episode duration). Genetic analyses evaluated the association between CYP2C19 variation and self-reported response, while polygenic score (PGS) analysis assessed whether genetic predisposition to psychiatric disorders and antidepressant response predicted self-reported SSRI outcomes.

71%–77% of participants reported positive responses to SSRIs. Non-response was significantly associated with alcohol and illicit drug use (OR = 1.59, p = 2.23 × 10−20), male gender (OR = 1.25, p = 8.29 × 10−08), and lower-income (OR = 1.35, p = 4.22 × 10−07). The worst episode lasting over 2 years (OR = 1.93, p = 3.87 × 10−16) and no mood improvement from positive events (OR = 1.35, p = 2.37 × 10−07) were also associated with non-response. CYP2C19 poor metabolizers had nominally higher non-response rates (OR = 1.31, p = 1.77 × 10−02). Higher PGS for depression (OR = 1.08, p = 3.37 × 10−05) predicted negative SSRI outcomes after multiple testing corrections.

Self-reported antidepressant response in the UK Biobank is influenced by sociodemographic, clinical, and genetic factors, mirroring clinical response measures. While positive outcomes are more frequent than remission reported in clinical trials, these self-reports replicate known treatment associations, suggesting they capture meaningful aspects of antidepressant effectiveness from the patient’s perspective.

To examine the incidence of asthma in adult patients with major depressive disorder (MDD).

From the National Health Insurance database of Taiwan, we identified 30 169 adult patients who were newly diagnosed with MDD between 2000 and 2010. Individuals without depression were randomly selected four times and frequency matched for sex, age and year of diagnosis. Both cohorts were followed-up for the occurrence of asthma up to the end of 2011. Adjusted hazard ratios (aHRs) of asthma were estimated using the Cox proportional hazards method.

The overall incidence of asthma was 1.91-fold higher in the MDD cohort than in the non-depression cohort (7.55 v. 3.96 per 1000 person-years), with an aHR of 1.66 (95% confidence interval (CI) 1.55–1.78). In both cohorts, the incidence of asthma was higher in patients and controls who were female, aged, with comorbidities and users of aspirin or beta-adrenergic receptor blockers. No significant difference was observed in the occurrence of asthma between patients with MDD treated with selective serotonin reuptake inhibitors (SSRIs) and those treated with non-SSRIs (SSRIs to non-SSRIs aHR = 1.03, 95% CI 0.91–1.17).

Adult patients with MDD are at a higher risk of asthma than those without depression are.

Antidepressants are frequently associated with treatment-emergent sexual dysfunction (TESD). Vortioxetine, which was approved for patients with major depressive disorder (MDD), has a receptor profile that suggests limited impact on sexual functioning.

Arizona Sexual Experiences Scale (ASEX) patient-level data were pooled from 7 short-term vortioxetine trials (6 in MDD, 1 in generalized anxiety disorder) and analyzed for incidence of TESD at any post-baseline visit in patients without sexual dysfunction at baseline (defined as ASEX total score ≥19; individual ASEX item score ≥5; or a score ≥4 on any 3 ASEX items). The primary objective was to confirm the non-inferiority of vortioxetine 5–20 mg/day to placebo on the incidence of TESD. Comparisons were based on the common risk difference (95% confidence interval). Additional analyses compared vortioxetine to duloxetine and duloxetine to placebo. A sensitivity analysis, defined as TESD at 2 consecutive post-baseline visits, was conducted.

TESD incidence, relative to placebo, generally increased with vortioxetine dose with vortioxetine 5 mg non-inferior to placebo. Vortioxetine 10, 15, and 20 mg did not meet the non-inferiority criterion, but no dose had a significantly higher risk of developing TESD versus placebo. Changes in ASEX individual item scores supported the similarity of vortioxetine doses to placebo. Significantly higher TESD risk occurred with duloxetine 60 mg/day versus placebo and versus vortioxetine 5 or 10 mg. The sensitivity analysis was generally consistent with the primary analysis. Rates of spontaneously reported sexual adverse events were low.

Vortioxetine was associated with rates of TESD that were not significantly different from placebo in short-term clinical trials.