Efficacy of repeated intravenous esketamine in adolescents with anxious versus non-anxious depression

Background Patients with anxious major depressive disorder(MDD)are more likely to have poorer outcomes than those with non-anxious MDD.However,the effect of esketamine on adolescents with anxious versus non-anxious MDD has remained unknown.Aims We compared the efficacy of esketamine in adolescents with MDD and suicidal ideation,both anxious and non-anxious.Methods Fifty-four adolescents with anxious(n=33)and non-anxious(n=21)MDD received three infusions of esketamine 0.25mg/kg or active-placebo(midazolam 0.045 mg/kg)over 5 days,with routine inpatient care and treatment.Suicidal ideation and depressive symptoms were assessed using the Columbia Suicide Severity Rating Scale and the Montgomery-Asberg Depression Rating Scale.Multiple-sample proportional tests were used to compare the differences between groups on treatment outcomes 24 hours after the final infusion(day 6,primacy efficacy endpoint)and throughout the 4-week post-treatment(days 12,19 and 33).Results In subjects who received esketamine,a greater number of patients in the non-anxious group than the anxious group achieved antisuicidal remission on day 6(72.7%vs 18.8%,p=0.015)and day 12(90.9%vs 43.8%,p=0.013),and the non-anxious group had a higher antidepressant remission rate compared with the anxious group on day 33(72.7%vs 26.7%,p=0.045).No significant differences in treatment outcomes were observed between the anxious and non-anxious groups at other time points.Conclusions Three infusions of esketamine as an adjunct to routine inpatient care and treatment had a greater immediate post-treatment antisuicidal effect in adolescents with non-anxious MDD than in those with anxious MDD;however,this benefit was temporary and was not maintained over time.