Background Coexisting anxiety is common in major depressive disorder (MDD) and more difficult to treat than depression without anxiety. This analysis assessed the efficacy, safety, and tolerability of vortioxetine in MDD patients with high levels of anxiety (baseline Hamilton Anxiety Rating Scale [HAM-A] total score ≥20). Methods Efficacy was assessed using an aggregated, study-level meta-analysis of 10 randomized, placebo-controlled, 6/8-week trials of vortioxetine 5–20 mg/day in adults (18–75 years), with a study in elderly patients (≥65 years) analyzed separately. Outcome measures included mean differences from placebo in change from baseline to endpoint (Δ) in the Montgomery-Åsberg Depression Rating Scale (MADRS), HAM-A total, and HAM-A subscales. Safety and tolerability were assessed by treatment-emergent adverse events (TEAEs). Results A total of 1497 (48.6%) vortioxetine-treated and 860 (49.1%) placebo-treated patients had baseline HAM-A≥20. There were significant differences from placebo in MADRS (vortioxetine 5 mg/day, n=415, Δ−2.68, P=0.005; 10 mg/day, n=373, Δ−3.59, P<0.001; 20 mg/day, n=207, Δ−4.30, P=0.005) and HAM-A total (5 mg/day, n=419, Δ−1.64, P=0.022; 10 mg/day, n=373, Δ−2.04, P=0.003; 20 mg/day, n=207, Δ−2.19, P=0.027). There were significantly greater improvements versus placebo on the HAM-A psychic subscale for all doses. The most common TEAEs (≥5.0%) were nausea, headache, dizziness, dry mouth, diarrhea, nasopharyngitis, constipation, and vomiting. Incidence of serious TEAEs was 1.3% (placebo) and ≤1.3% (vortioxetine, across doses). Limitations Study heterogeneity limits this analysis. Patients with baseline HAM-A≥20 were not directly compared to baseline HAM-A<20 or total MDD population. Conclusions Vortioxetine was efficacious in reducing depressive and anxiety symptoms in patients with MDD and high levels of anxiety.
