A Beacon of Hope: Esketamine's Rapid Impact on Suicidal Adolescents

When a young person is struggling with severe depression and thoughts of suicide, time is of the essence. The pain can be overwhelming, and the need for effective, fast-acting treatment is critical. For families and individuals navigating this terrifying landscape, the search for hope can feel desperate. It is in this context that emerging research into treatments like esketamine nasal spray offers a potential beacon, a new avenue for rapidly alleviating depressive symptoms in adolescents at imminent risk for suicide. If you are exploring options for psychedelic psychotherapy, or are simply seeking to understand the latest advancements in mental health care for young people, this information is vital. Adolescent depression is a serious and unfortunately common mental health challenge. Major Depressive Disorder (MDD) is a leading cause of disability among young people and is tragically the condition most frequently linked to suicide (Kosik-Gonzalez et al., 2025; Pardossi et al., 2024). Statistics paint a grim picture: a significant percentage of high school students report seriously considering suicide, and many have made an attempt (Canuso, 2023). For those who attempt suicide, up to 80% meet the criteria for MDD at that time (Canuso, 2023; Kosik-Gonzalez et al., 2025). The urgency is compounded by the fact that the window between the onset of suicidal thoughts and an attempt can be terrifyingly short (Kosik-Gonzalez et al., 2025).

The Challenge of Treating Acute Suicidality in Youth

Traditionally, treating adolescents with MDD who are at immediate risk of suicide involves a combination of hospitalization for safety, standard antidepressant medications, and evidence-based psychotherapy (Kosik-Gonzalez et al., 2025). While these interventions are crucial, they each have limitations. Standard antidepressants, for example, can take four to six weeks to reach their optimal effect in improving mood – a dangerously long time for someone in acute crisis (Kosik-Gonzalez et al., 2025). Access to specialized psychotherapy can also be a hurdle, and even hospitalization, while providing immediate safety, doesn't eliminate the risk, which can remain high even after discharge (Kosik-Gonzalez et al., 2025).Furthermore, there has been a significant gap in pharmacological treatments specifically approved for adolescents with MDD at imminent suicide risk. Often, individuals with acute suicidal thoughts or behaviors are excluded from antidepressant clinical trials, leaving a critical unmet need for this vulnerable population (Canuso, 2023; Kosik-Gonzalez et al., 2025).

Esketamine: A New Approach Offering Rapid Relief

This is where esketamine, a nasal spray formulation of a compound related to ketamine, is showing promise. Esketamine works differently than traditional antidepressants. It is an N-methyl-D-aspartate (NMDA) receptor antagonist. Studies in adults with MDD and acute suicidal ideation or behavior have already demonstrated that esketamine, when used alongside an oral antidepressant, can lead to a rapid reduction in depressive symptoms, often within 24 hours of the first dose (Canuso, 2023; Kosik-Gonzalez et al., 2025).A pivotal phase 2b study, published in the Journal of the American Academy of Child & Adolescent Psychiatry, specifically investigated the efficacy and safety of esketamine nasal spray in adolescents (ages 12 to <18 years) with MDD who were at imminent risk for suicide (Kosik-Gonzalez et al., 2025). This double-blind, psychoactive-controlled study (meaning it was compared against midazolam, a substance with some sedative effects, to help ensure the blinding" of the study was maintained) randomized 147 adolescents to receive either esketamine (at doses of 28mg, 56mg, or 84mg) or midazolam, administered twice weekly for four weeks. Crucially, all participants also received comprehensive standard of care, which included initial hospitalization, an oral antidepressant, and evidence-based psychotherapy (Kosik-Gonzalez et al., 2025).The primary goal was to see if esketamine could rapidly reduce depressive symptoms, measured by the Children’s Depression Rating Scale–Revised (CDRS-R), within 24 hours after the first dose. The results were significant. The pooled esketamine doses (specifically the 56mg and 84mg doses) showed superiority over midazolam in reducing these depressive symptoms at that critical 24-hour mark (Kosik-Gonzalez et al., 2025). While the severity of suicidality itself improved across all treatment groups (including the placebo group, likely due to the comprehensive standard of care everyone received), the rapid impact on depressive symptoms by esketamine is a key finding (Kosik-Gonzalez et al., 2025; Canuso, 2023).Dr. Carla Canuso, involved in the research, highlighted that this was the first global, multi-center pharmacological treatment trial in adolescent patients with MDD and acute suicidal ideation and behavior (Canuso, 2023). This is groundbreaking because, as mentioned, this population is often excluded from such research. The study not only showed promising results for esketamine but also demonstrated that such research can be conducted safely and ethically with appropriate monitoring and study design (Canuso, 2023).

Understanding Esketamine: Safety and Administration

Of course, with any potent medication, especially one used in a vulnerable population, safety is paramount. The study reported that common adverse events for esketamine included dizziness, nausea, dissociation (a feeling of detachment from oneself or reality), headache, altered taste, drowsiness, vomiting, and hypoesthesia (reduced sense of touch) (Kosik-Gonzalez et al., 2025). Importantly, Dr. Canuso noted that no new or unexpected safety concerns were observed in adolescents compared to what has been seen in adult trials (Canuso, 2023). Dissociation, a characteristic side effect, is typically transient, peaking around 40 minutes after treatment and usually resolving within 1.5 hours (Canuso, 2023).Esketamine nasal spray is administered under the direct supervision of a healthcare provider, both in clinical trials and in practice. In this study, participants, who were initially hospitalized, were able to self-administer the nasal spray under supervision, and adherence to the treatment regimen (two doses per week for four weeks) was very high, with approximately 95% completing the course (Canuso, 2023).It is also important to note that esketamine does have the potential for abuse and misuse. Therefore, clinicians must carefully consider the risks and benefits for any patient, particularly those with a higher risk of substance abuse. Studies typically exclude individuals with a recent history of moderate or severe substance or alcohol use disorder (Canuso, 2023).

A Window of Opportunity

The rapid reduction of depressive symptoms offered by esketamine can be seen as creating a crucial "window of opportunity." As a systematic review by Pardossi et al. (2024) on ketamine and esketamine for treatment-resistant depression and suicidality in adolescents suggests, these drugs can effectively treat symptoms, reduce self-harm and suicide risks, and provide a critical period for longer-term therapeutic interventions to take hold. While the immediate crisis is addressed, the comprehensive standard of care, including ongoing antidepressant medication and psychotherapy, remains essential for sustained recovery. The journey through adolescent depression, especially when accompanied by suicidal thoughts, is incredibly challenging. The emergence of treatments like esketamine nasal spray, demonstrating rapid efficacy in reducing depressive symptoms, offers a significant advancement and a source of hope. It underscores the importance of continued research and the development of innovative treatments tailored to the unique needs of young people in crisis. For those uncertain about psychedelic psychotherapy, understanding that some of these compounds, or their derivatives like esketamine, are being rigorously studied and integrated into mainstream psychiatric care under strict medical supervision can be reassuring. This research is not about unsupervised experimentation but about carefully harnessing the potential of these substances to save lives and alleviate profound suffering. As research progresses, likely moving into Phase 3 confirmatory trials for adolescents (Canuso, 2023), the hope is that more effective and rapidly acting treatments will become available, offering a brighter future for young people facing the darkest of times.

Disclaimer: Psychedelic Assisted Psychotherapy has not been approved by any regulatory agencies in the United States, and the safety and efficacy are still not formally established at the time of this writing.

References

Canuso, C. (2023, December 12). New Data on Esketamine Nasal Spray as Treatment for Adolescents Contemplating Suicide. Psychiatric Times. https://www.psychiatrictimes.com/view/new-data-esketamine-nasal-spray-as-treatment-for-adolescents-contemplating-suicide

Kosik-Gonzalez, C., Fu, D.-J., Chen, L. N., De Bruecker, G., Lavenstein, B., Bi, M., Singh, J., Pinter, C., Wilkinson, S. T., Van Der Gucht, K., Pathak, S., Fedgchin, M., DeJonghe, B. C., Moreno, C., Drevets, W. C., & Canuso, C. M. (2025). Effect of Esketamine on Depressive Symptoms in Adolescents With Major Depressive Disorder at Imminent Suicide Risk: A Randomized Psychoactive-Controlled Study. Journal of the American Academy of Child & Adolescent Psychiatry. Published online March 6, 2025. https://doi.org/10.1016/j.jaac.2025.01.019)

Pardossi, S., Fagiolini, A., Scheggi, S., & Cuomo, A. (2024). A Systematic Review on Ketamine and Esketamine for Treatment-Resistant Depression and Suicidality in Adolescents: A New Hope?. Children (Basel, Switzerland), 11(7), 801. https://doi.org/10.3390/children11070801  (https://pubmed.ncbi.nlm.nih.gov/39062250/ )