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Home/Research/Esketamine/Older Adults

Esketamine for Older Adults

8 papers and 2 clinical trials exploring esketamine as a treatment for older adults.

Compounddissociative

Esketamine

Esketamine (Spravato) is the S-enantiomer of ketamine, approved as an intranasal treatment for treatment-resistant depression and MDD with acute suicidal ideation. It is administered under clinical supervision with post-dose monitoring and has reached over $1.6 billion in annual sales.

Full Esketamine profile
IndicationApproximately 300 million adults worldwide struggle with depression, many of whom are older adults.

Older Adults

Psychedelic research involving older adults is gaining traction, highlighting the potential therapeutic benefits of compounds such as psilocybin and MDMA. Recent studies suggest promising safety profiles and efficacy, paving the way for future clinical applications in this demographic.

Full Older Adults profile

Academic Research

8 papers
Open Accessmeta

Control Group Outcomes in Trials of Psilocybin, SSRIs, or Esketamine for Depression: A Meta-Analysis

This meta-analysis of 17 trials found that control-group participants in psilocybin depression trials showed markedly smaller improvements (SMC ≈ 0.50) on the MADRS than control participants in SSRI (SMC ≈ 1.00) or esketamine (SMC ≈ 1.12) trials. The authors conclude this disparity may indicate that psilocybin’s antidepressant efficacy is overestimated relative to SSRIs and esketamine, possibly because of functional unblinding and expectancy effects.

Published
July 30, 2025
Journal
JAMA Network Open
Authors
Hieronymus, F., López, E., Sjögren, H. W., Lundberg, J.
Paywallindividual

Esketamine nasal spray versus quetiapine XR in adults with treatment-resistant depression: a secondary analysis of the ESCAPE-TRD randomized clinical trial

In a secondary analysis of ESCAPE-TRD (n=636), esketamine nasal spray plus an oral antidepressant, dosed according to US prescribing information, produced significantly higher remission rates from week 8 to week 32 and greater, earlier reductions in MADRS scores (from day 8) than quetiapine XR, with fewer discontinuations due to adverse events.

Published
January 17, 2025
Journal
CNS Spectrums
Authors
McIntyre, R. S., Mattingly, G., Godinov, Y., Buyze, J., Turkoz, I., Cabrera, P., Patel, M., Martinez, L., Himedan, M., Lopena, O.
Paywallindividual

Effect of Repeated Intravenous Esketamine on Adolescents With Major Depressive Disorder and Suicidal Ideation: A Randomized Active-Placebo-Controlled Trial

This placebo-controlled trial (n=54) investigates the efficacy and safety of esketamine (iv, 17.5mg, 3x) in adolescents suffering from depression (MDD) and suicidal ideation (SI). It shows significant reductions in Columbia Suicide Severity Rating Scale (C-SSRS) Ideation and Intensity scores and Montgomery-Åsberg Depression Rating Scale (MADRS) scores in the esketamine group compared to the midazolam (placebo) group at day six, with maintained antisuicidal and antidepressant responses at four weeks post-treatment.

Published
May 1, 2024
Journal
Child and Adolescent Psychiatry
Authors
Zhou, Y., Lan, X-F., Wang, C., Zhang, F., Liu, H., Chao, Z., Ning, Y-P., Fu, L., Hu, Z., Li, W., Ye, Y.
Open Accessindividual

Short-term cognitive effects of repeated-dose esketamine in adolescents with major depressive disorder and suicidal ideation: a randomized controlled trial

In a randomised controlled trial of 51 adolescents with major depressive disorder and suicidal ideation, three subanaesthetic esketamine infusions (0.25 mg/kg) did not impair cognition and were associated with improved processing speed and some improvement in working memory by Day 12. Baseline cognitive performance did not predict antidepressant or antisuicidal response.

Published
September 14, 2023
Journal
Child and Adolescent Psychiatry
Authors
Lan, X-F., Wang, C-Y., Zhang, F., Liu, H., Mai, S., Ning, Y-P., Zhou, Y-L., Hu, Z., Li, W., Ye, Y.
Open Accessindividual

Esketamine vs Midazolam in Boosting the Efficacy of Oral Antidepressants for Major Depressive Disorder

In this single-centre pilot randomised, double-blind trial of 30 adults with major depressive disorder and fluctuating antidepressant response, a single subanaesthetic intravenous dose of esketamine (0.2 mg/kg) added to ongoing oral antidepressants produced markedly higher 2-week response rates (66.7% vs 6.7%) and greater reductions in MADRS scores than midazolam. No serious adverse events, psychotomimetic effects, or clinically significant manic symptoms were observed.

Published
August 14, 2023
Journal
JAMA Network Open
Authors
Xiao, C., Zhou, J., Zhu, X., Liu, J., Deng, Q., Wang, G., Wang, H., Hu, Y., Li, A.
Open Accessindividual

Efficacy and Safety of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression Who Completed a Second Induction Period: Analysis of the Ongoing SUSTAIN-3 Study

This subgroup analysis of SUSTAIN-3 (n=96) studies patients with treatment-resistant depression (TRD) who received a second induction and maintenance treatment with esketamine nasal spray (ESK) plus oral antidepressant (AD) after a relapse in SUSTAIN-1.

Published
August 9, 2023
Journal
CNS Drugs
Authors
Castro, M., Wilkinson, S. T., Al Jurdi, R. K., Petrillo, M. P.z, Sun, L., Zaki, N., Borentain, S., Turkoz, I., Brown, B., Cabrera, P., Fu, D. J.

Clinical Trials

2 trials
RecruitingPhase NA

Effect of Low-dose Esketamine on Delirium in High-risk Elderly Patients Undergoing Elective Surgery (ELEMENT)

Double-blind, placebo-controlled randomised trial (n=1670) testing low-dose intraoperative and postoperative esketamine versus placebo to prevent postoperative delirium in high-risk elderly patients undergoing major non-cardiac surgery.

Started
February 1, 2025
Type
interventional
Blinding
double
Randomized
Yes
Registry ID
NCT06817239
CompletedPhase III

A Study to Evaluate the Efficacy, Safety, and Tolerability of Intranasal Esketamine Plus an Oral Antidepressant in Elderly Participants With Treatment-resistant Depression (TRANSFORM-3)

Randomized, double-blind, active-controlled Phase III study (n=139) in elderly participants with TRD testing intranasal esketamine (flexible 28–84 mg, twice weekly for 4 weeks) plus a new oral antidepressant versus intranasal placebo plus a new oral antidepressant.

Started
August 20, 2015
Type
interventional
Blinding
double
Randomized
Yes
Registry ID
NCT02422186

Explore further

Search all Esketamine papers Search all Older Adults trials Full Esketamine profile Full Older Adults profile