Effects of Ketamine vs. Midazolam in Adolescent Treatment Resistant Depression

<b>Background:</b> Adolescent treatment resistant depression (TRD) is increasing in recent years. While ketamine showed rapid antidepressant effects in adult TRD studies, research on its effectiveness in adolescents is limited. <b>Methods:</b> This study examines the effects of intravenous ketamine vs. midazolam on depressive and anxiety symptomatology assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), and Children's Depression Inventory (CDI) at two time points-2 h after initial infusion (T0+2h) and 24 h after the end of the treatment (Te+24h) in a sample of 55 adolescent TRD females (27 receiving ketamine, 28 midazolam). <b>Results:</b> At T0+2h, within-group comparisons revealed a significant reduction in MADRS and HAM-A scores compared to baseline in the ketamine and midazolam groups. At Te+24h, both groups demonstrated similar significant reductions in MADRS, HAM-A, and CDI scores compared to baseline. The MADRS assessment in the ketamine group showed 33% and 59% responders, and in the midazolam group, 14% and 46% responders at T0+2h and Te+24h, respectively. HAM-A evaluation in the ketamine group revealed 33% and 56% responders, and in the midazolam group, 11% and 39% responders at T0+2h and at Te+24h, respectively. CDI rating discovered 11% and 44% responders in the ketamine group and 4% and 21% responders in the midazolam group at T0+2h and Te+24h, respectively. Moreover, inner tension significantly decreased in ketamine compared to the midazolam group at Te+24h. <b>Conclusions:</b> Ketamine showed a reduction in depressive and anxiety symptoms during a short-term period with particular efficacy in alleviating inner tension over midazolam, suggesting its potential advantages in specific symptom relief in rarely studied adolescent TRD.