Objective. A comparative evaluation of the efficacy and safety of different types of pharmacotherapy: antidepressant monotherapy (agomelatine or sertraline), mood stabilizer monotherapy (valproate) and combination therapy (valproate + sertraline) in bipolar II disorder patients with major depressive episode. Material and methods. A 6-week open randomized study included 89 inpatients and outpatients. Basic criteria of efficacy were ≥50% reduction of HAMD total score and remission (≤7 points) to the end of the study. Results. At the end of the study (day 42), the highest number of patients with 50% reduction of HAMD total score was noted in the sertraline (65%) and combination therapy (60%) groups, in the valproate group it was 57.1%, and the lowest — in agomelatine group (42.9%), but the differences were not statistically significant. Remission was observed in 45% patients in combination therapy group compared with 33.3% in valproate group, 32.1% in agomelatine group and only 20% in group of sertraline, but the differences between the groups also were not significant. Conclusion. Antidepressants (agomelatine and sertraline) have demonstrated fast but insufficient influence on the reduction of depression in the patients. Treatment with sertraline rarely led to remission and was frequently associated with high rate of switch into hypomania. Valproate therapy was moderately effective and well-tolerated without risk of switching. Combination of valproic acid with sertraline had the highest efficacy and was fairly well tolerated.