ObjectiveThis study aimed to explore both impairments in attention function in patients with major depressive disorder (MDD) and the efficacy of escitalopram monotherapy or combination therapy with agomelatine.MethodsA total of 54 patients with MDD and 46 healthy controls (HCs) were included. Patients were treated with escitalopram for 12 weeks; those who presented with severe sleep impairments were also given agomelatine. Participants were evaluated using the Attention Network Test (ANT), which included tests of alerting, orienting, and executive control networks. Concentration, instantaneous memory, and resistance to information interference were tested using the digit span test, and the logical memory test (LMT) was used to evaluate abstract logical thinking. The Hamilton Depression Rating Scale−17 items, Hamilton Anxiety Rating Scale, and Pittsburgh Sleep Quality Index were used to assess depression, anxiety, and sleep quality, respectively. Patients with MDD were assessed at the end of weeks 0, 4, 8, and 12. HCs were assessed once at baseline.ResultsCompared with HCs, patients with MDD showed significantly different alerting, orienting, and executive control functions of attention networks. Treatment with escitalopram alone or combined with agomelatine significantly improved LMT scores at the end of weeks 4, 8, and 12 and restored scores to the level of HCs at the end of week 8. Total Toronto Hospital Test of Alertness scores in patients with MDD increased significantly after 4 weeks of treatment. The ANT executive control reaction time in patients with MDD decreased significantly after 4 weeks of treatment, with this decrease lasting until the end of week 12, but scores did not return to the levels of HCs. Combined treatment with escitalopram and agomelatine led to more improvement in ANT orienting reaction time and was accompanied by a greater reduction of total scores on the Hamilton Depression Rating Scale−17 items and Hamilton Anxiety Rating Scale compared with escitalopram monotherapy.ConclusionsPatients with MDD showed overall impairments in three domains of attention networks as well as the LMT and a test of subjective alertness. Escitalopram monotherapy significantly improved the LMT scores and the executive control function scores in the ANT at the end of the fourth week of treatment, and the improvement was more extensive with combined escitalopram and agomelatine treatment.