Suicide is the second leading cause of death in the United States among individuals aged 10-24, and severe youth depression is often refractory to the current standards of care. Many studies have demonstrated the efficacy of ketamine in reducing depressive symptoms in adults with treatment-resistant mood disorders, though few studies utilizing ketamine in youth populations exist. This systematic review examines the current state of evidence for ketamine use in children with treatment-resistant mood disorders. We conducted a search utilizing two electronic databases for English-language studies investigating the therapeutic effects and side effect profile of ketamine in youth ≤ 19 years of age with a diagnosis of a treatment-resistant mood disorder. Analysis included subjects with treatment-resistant depression with and without psychotic features and with bipolar disorder. Primary outcome measures included the following scales: Montgomery-Asberg Depression Rating Scale, Children's Depression Rating Scale, Children's Depression Rating Scale Revised, Child Bipolar Questionnaire, Overt Aggression Scale, Yale-Brown Obsessive-Compulsive Scale, and Scale for Suicidal Ideation. Four published studies were identified that investigated therapeutic ketamine use in youth for the primary purpose of treating a treatment-resistant psychiatric disorder. Three additional studies that did not meet eligibility criteria were identified and discussed. Ketamine was shown in youth to generally improve depressive symptoms, decrease acute suicidality, and reduce mood lability, though a number of subjects remained resistant to its treatment. These findings substantiate the need for further longitudinal studies investigating ketamine's long-term safety, its efficacy, and abuse potential in the youth.
Keywords: Esketamine; Ketamine; Treatment-resistant bipolar disorder; Treatment-resistant depression; Treatment-resistant psychiatric disorders.