Adolescent major depressive disorder (MDD) is a leading cause of disability worldwide and a major, modifiable risk factor for suicide, which remains the second leading cause of death in this age group.1 For 30% to 50% of patients who fail to achieve remission despite multiple treatment steps, the clinical and psychosocial consequences are substantial.2 Although selective serotonin-reuptake...
Objective: To investigate neurobiological mechanisms through which esketamine produces rapid antidepressant effects in adolescents with major depressive disorder (MDD), focusing on structural changes in the rostral anterior cingulate cortex (rACC) and associated molecular pathways. Method: A total of 49 adolescents (13-18 years of age) with DSM-5 MDD were randomized to receive intravenous...
We read with interest the Commentary by Jeffrey et al. encouraging clinical research using psychedelics for adolescents.1 Throughout their commentary, the authors operate under the general presupposition that psychedelics have demonstrated a favorable safety profile in adults, and that therefore teenagers approaching an adult level of neurodevelopment can likely be safely treated with...
To evaluate the efficacy, safety, and tolerability of esketamine nasal spray vs psychoactive placebo (oral midazolam) in rapidly reducing depressive symptoms in adolescents with major depressive disorder at imminent risk for suicide. This double-blind, double-dummy, phase 2b study randomized (1:1:1:2) 147 adolescents (12 to <18 years old) to esketamine (28, 56, or 84 mg) or midazolam twice...
We read with great interest the commentary by Jeffrey et al. entitled "Clinical Research Trials of Psychedelic-Assisted Therapy in Adolescents Aged 16 to 17 Years: Rationale Balanced With Caution."1 We appreciate the efforts of the authors, the scholarship of this commentary, and the advocacy for research initiatives with psychedelic therapeutics such as psilocybin, lysergic acid diethylamide,...
We are writing in response to 2 Letters to the Editor, both of which discussed our commentary, entitled "Clinical Research Trials of Psychedelic-Assisted Therapy in Adolescents Aged 16 to 17 Years: Rationale Balanced With Caution."1 We appreciate the thoughtful responses to our commentary, and we invite further dialogue about this important subject. Both letters emphasized the importance in...
Youth today are burdened by significant mental health challenges. In 2022, 25% of adolescents aged 12 to 17 years experienced a mental illness, with 20% experiencing a depressive episode, 12.5% reporting serious thoughts of suicide, and 17% meeting criteria for a substance use disorder.1 Close to 5% of adolescents experience posttraumatic stress disorder.2 Impairing psychiatric symptoms remain...
Suicide continues to be a major cause of mortality in adolescents with limited treatment options.1,2 Effective treatments, both therapy and medication, are available for treating depression, but even with the best combination, treatment remission rates are low.3 The most common approach to treating suicidality, which includes suicidal ideation and suicidal behavior, is to address concomitant...
Suicide is a major cause of death in adolescents with limited treatment options. Ketamine and its enantiomers have shown rapid anti-suicidal effects in adults with major depressive disorder (MDD), but their efficacy in adolescents is unknown. We conducted an active, placebo-controlled trial to determine the safety and efficacy of intravenous esketamine in this population. A total of 54...
Amid rising national rates of childhood depression and anxiety,1,2 the development and accessibility of therapeutic psychosocial interventions for children have taken on paramount importance. Given the limited bandwidth of the existing clinical mental health services nationally, there is also an imperative to integrate therapeutic interventions within nonclinical, community-based settings (eg,...
Objective: Understanding the fluctuating emotional and cognitive states of adolescents with depressive symptoms requires fine-grained and naturalistic measurements. This study used ecological momentary assessment (EMA) to investigate the affective correlates and consequences of mind-wandering in adolescents with anhedonia (AH) and typically developing (TD) controls. In addition, we examined the...
This review of the scientific literature examines the potential adult sequelae of exposure to cannabis and related synthetic cannabinoids in adolescence. We examine the four neuropsychiatric outcomes that are likely most vulnerable to alteration by early cannabinoid use, as identified within both the clinical and preclinical research: cognition, emotional functioning, risk for psychosis, and...