New data on esketamine nasal spray for treating suicidal adolescents

Q&A

Data from a new study showing the use of esketamine among adolescents at imminent risk of suicide were presented at the American College of Neuropsychopharmacology (ACNP) 2023 Annual Meeting. era of psychiatry Sit down with Carla Canuso, MD, to discuss key findings and more.

PT: Can you talk about the worrying trend of teen suicide? What did this question teach you and your co-authors?

Canuso: Suicide is the leading cause of death among adolescents worldwide.1 As of 2020, 18.8% of high school students reported seriously considering suicide and 8.9% had attempted it, according to the Centers for Disease Control and Prevention.2 Up to 80% of adolescents who attempt suicide meet criteria for major depressive disorder (MDD) at the time of the attempt3-6 Up to 60% of teenagers who commit suicide suffer from depression.7,8 There are currently no approved pharmacological treatments for adolescents who urgently need rapid relief from depressive symptoms. Studies of adults with major depression who experience acute suicidal ideation and behavior show that adding esketamine nasal spray to an SSRI or SNRI oral antidepressant can significantly reduce depressive symptoms within 24 hours of treatment.9 These results inspired us to study esketamine in suicidal adolescents with major depression, a vulnerable and understudied population with large unmet medical needs.

Our interest in studying esketamine nasal spray in adolescent populations is also consistent with regulatory requirements in the United States and the European Union.

PT: Your data evaluate the safety and effectiveness of esketamine nasal spray in the treatment of major depression in adolescent patients. Can you share some highlights from the data above?

Canuso: On average, pooled data from adolescent patients who received 56 mg and 84 mg of esketamine nasal spray added to an SSRI showed fewer depressive symptoms 24 hours after the first dose compared with patients who received a psychoactive comparator (midazolam). Clinically meaningful and statistically significant improvements were achieved. ) added to SSRI.

On average, patients in all treatment groups experienced a reduction in the severity of suicidality within 24 hours of their first dose of study drug. However, the difference between groups did not reach statistical significance.

No new or unexpected safety concerns were observed in adolescents, which is consistent with results observed in previous trials of adults with major depression who had suicidal ideation or behavior.

PT: How does esketamine compare to other treatments in terms of safety, effectiveness, and response time?

Canuso: Esketamine nasal spray is approved in the United States for the treatment of adult patients with treatment-resistant depression (TRD) and major depressive disorder (MDD) with acute suicidal ideation and behavior (MDSI). The effectiveness of esketamine nasal spray in preventing suicide or reducing suicidal ideation or behavior has not been proven. Esketamine nasal spray is the only treatment approved to treat depressive symptoms within 24 hours of the first dose and is the only treatment approved for MDSI.

The Phase 2 study of esketamine in adolescents presented at ACNP is the first multicenter, global study of this important patient population. There are no comparative studies of esketamine nasal spray in adolescents. A recently published study comparing esketamine nasal spray and quetiapine (added to an SSRI/SNI, respectively) in the treatment of adults with TRD found that esketamine nasal spray significantly improved remission rates of depressive symptoms at 8 weeks, and at Among study participants who were in remission, the rate of remission of depressive symptoms was significantly reduced. Relapse occurred at 32 weeks.

Esketamine has a distinct adverse effect profile that is generally consistent in adults and adolescents. Dissociation, or the feeling of being disconnected from oneself, is a unique adverse effect that is transient (peaks approximately 40 minutes after treatment and usually subsides within 1.5 hours of treatment). Other transient adverse reactions include dizziness, drowsiness, nausea and a bitter taste.

PT: How do adolescent patients feel about nasal sprays compared to oral medications? Should clinicians be concerned about issues related to compliance?

Canuso: Esketamine nasal spray is used under the direct supervision of a healthcare provider, whether in clinical practice or in a research setting. In studies of adolescents with suicidal ideation or behavior, participants were initially hospitalized for severe psychiatric conditions. Study participants were able to self-administer the nasal spray, and nearly all (approximately 95%) were able to complete treatment, which consisted of two doses per week for four weeks.

PT: According to research, who is the ideal patient? Under what circumstances might it be contraindicated?

Canuso: In our study, adolescent patients had moderate to severe depression at baseline, and most were assessed as having significant or severe suicidality. All patients required hospitalization, and more than two-thirds had attempted suicide in the past month. When selecting a drug, clinicians consider each patient’s benefit-risk equation, including severity of symptoms and risks of the condition.

Because esketamine has the potential for abuse and misuse, the risks and benefits of this drug should be carefully considered in any patient who is at increased risk for abuse. Our studies of esketamine nasal spray generally excluded patients with a recent history of moderate or severe substance or alcohol use disorders, as well as patients with a lifetime history of ketamine or psychedelic drug-related (i.e., LSD, PCP, MDMA) use disorders.

Esketamine nasal spray is contraindicated in patients with a known aneurysm, arteriovenous malformation, or a history of intracerebral hemorrhage due to the risk of increased blood pressure.

PT: This study is the first trial of a drug treatment in this patient population. What does it mean to you to break ground in this way?

Canuso: To our knowledge, this is the first global trial of a pharmacological treatment in adolescent patients with acute suicidal ideation and behavior. Adolescent patients at risk for suicide are often excluded from clinical trials of antidepressant drugs. The findings not only hold promise that esketamine nasal spray can rapidly reduce depressive symptoms in this vulnerable and understudied population, but also that (with appropriate monitoring and study design) these patients can safely and ethically participate in clinical research . This could open the door to future treatments for this important group of patients.

PT: How do you think esketamine nasal spray should be further studied in treating adolescents with depression?

Canuso: Consistent with regulatory requirements and an agreed pediatric development plan, we will enter Phase 3 to generate validation data for esketamine nasal spray in adolescents with major depression experiencing acute suicidal ideation or behavior.

PT: How important is it to you that these findings were presented at the American College of Neuropsychopharmacology (ACNP) 2023 Annual Meeting?

Canuso: The ACNP Annual Meeting is the premier venue dedicated to advancing scientific understanding of and promoting communication about brain disease and behavior to advance their prevention and treatment. Presentation at this meeting will enable our data to reach basic, translational, and clinical researchers as we work together toward the collective goal of improving brain health.

This meeting provided the opportunity to share long-term safety data on esketamine nasal spray in more than 1,000 adult patients with TRD, some of whom were followed for up to 6.5 years of treatment.10

Dr. Canuso is vice president and head of neuropsychiatric clinical development at Johnson & Johnson Innovative Medicines.

refer to

1. Youth mental health. World Health Organization. November 17, 2021. Viewed December 8, 2023. https://www.who.int/news-room/fact-sheets/detail/adolescent-mental-health

2. Internet-based injury statistics query and reporting system. CDC. 2020. Date viewed: December 8, 2023. https://www.cdc.gov/injury/wisqars/index.html

3. Gould MS, King R, Greenwald S, et al. Psychopathology associated with suicidal ideation and attempts in children and adolescents. J Am Acad Child Adolescent Psychiatry. 1998;37(9):915-923.

4.Nock MK, Green JG, Hwang I, et al. Prevalence, correlates, and treatment of lifetime suicidal behavior in adolescents: Results from the National Comorbidity Survey Replication Adolescent Supplement. JAMA Psychiatry. 2013;70(3):300-310.

5. Beautrais AL, Joyce PR, Mulder RT. Psychiatric disorders in a New Zealand sample of young people with serious suicide attempts. New Zealand Medicine J. 1998;111(1060):44-48.

6. Goldston DB, Daniel SS, Reboussin BA, et al. Psychiatric diagnoses in previous suicide attempts, first-time suicides, and repeat suicides in adolescent inpatient psychiatry units. J Am Acad Child Adolescent Psychiatry. 1998;37(9):924-932.

7. Brent DA, Baugher M, Bridge J, et al. Age- and gender-related risk factors for adolescent suicide. J Am Acad Child Adolescent Psychiatry. 1999;38(12):1497-1505.

8. Shaffer D, Gould MS, Fisher P, et al. Psychiatric diagnosis of suicide in children and adolescents. Arch Gen Psychiatry. 1996;53(4):339-348.

9. Canuso CM, Ionescu DF, Li X, et al.. Esketamine nasal spray is used to rapidly reduce the depressive symptoms of major depression associated with acute suicidal ideation or behavior. Journal of Clinical Psychopharmacology.2021;41(5):516-524.

10. Fu DJ, Zaki N, Chen L, et al. ACNP2023. annual meeting. Poster T121.

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