Baseline perceived stress as a predictor of ketamine/esketamine treatment response in treatment-resistant depression.
Stefanie Cavalcanti, Vanessa K Pazdernik, Jennifer L. Vande Voort, Simon Kung, Balwinder Singh
Journal of Affective Disorders August 15, 2025 DOI: 10.1016/j.jad.2025.04.117 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Historical cohort study Peer reviewed |
|---|---|
| Sample size | 39 |
| Population | Adult patients with treatment-resistant depression receiving intravenous racemic ketamine or intranasal esketamine |
| Interventions | Intravenous racemic ketamine Intranasal esketamine |
| Topics | Ketamine Depression Esketamine |
| Keywords | Mood disorders Ketamine therapy Stress response Depression treatment Mental health interventions |
| Citations | 3 |
| Key findings | Higher baseline perceived stress was associated with lower odds of remission and more treatments needed for remission in treatment-resistant depression patients receiving ketamine or esketamine. |
Abstract
Chronic stress is a risk factor for depression and may contribute to treatment resistance. This historical cohort study examined the association between baseline perceived stress, measured with the Perceived Stress Scale (PSS), and response to (es) ketamine in treatment-resistant depression (TRD). Adult TRD patients who received intravenous racemic ketamine or intranasal esketamine were included. Depression symptoms were evaluated using the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR). Baseline stress was assessed using the PSS, with scores categorized into low to moderate (PSS < 27) and high (PSS ≥ 27) stress. Statistical tests, including Pearson correlation, Fisher's exact test, and Kruskal-Wallis tests, were used to explore associations between baseline stress, remission (QIDS-SR ≤ 5), and the number of treatments required for remission. Firth's logistic regression model estimated odds ratios (ORs) and 95 % confidence interval (CI). Among 39 patients (median age 47, 61.5 % female), 66.7 % had high perceived stress. Patients with high PSS scores required more treatments for remission (median = 3 vs. 1, p = 0.04). Each 5-point PSS increase reduced remission odds by 60 % (OR = 0.40, 95 % CI: 0.14-0.81, p = 0.009), adjusting for stimulant use. Notably, these effects were independent of baseline depression severity. The study's observational design and lack of a placebo group limit the findings. TRD patients with high baseline perceived stress had lower odds of remission, and required more treatments to achieve remission. Further research should investigate whether stress-reduction strategies combined with ketamine could enhance treatment outcomes and whether responses differ between acute and chronic perceived stress.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cited by 3
- Clinical Predictors of Antidepressant Effects of Ketamine and Esketamine in Treatment-Resistant Unipolar and Bipolar Depression: A Systematic Review CNS Drugs July 1, 2026
- Early suicidal ideation change and suicidality-associated emergency department utilization after ketamine or esketamine treatment in treatment-resistant depression. Therapeutic Advances in Psychopharmacology May 22, 2026
- Hepatic Safety of Ketamine and Esketamine for Treatment-Resistant Depression: A Real-World Cohort Study. Journal of Clinical Psychopharmacology July 28, 2026
Cites 11
- Ketamine rapidly reverses stress-induced impairments in GABAergic transmission in the prefrontal cortex in male rodents Neurobiology of Disease November 7, 2019
- Comparative Effectiveness of Intravenous Ketamine and Intranasal Esketamine in Clinical Practice Among Patients With Treatment-Refractory Depression: An Observational Study. The Journal of Clinical Psychiatry February 1, 2023
- Evaluation of the Trajectory of Depression Severity With Ketamine and Esketamine Treatment in a Clinical Setting JAMA Psychiatry May 11, 2022
- Change in neurocognitive functioning in patients with treatment-resistant depression with serial intravenous ketamine infusions: The Bio-K multicenter trial. Psychiatry Research May 1, 2024
- Efficacy of Ketamine with and without Lamotrigine in Treatment-Resistant Depression: A Preliminary Report Pharmaceuticals August 1, 2023
and 6 more in the library