Baseline perceived stress as a predictor of ketamine/esketamine treatment response in treatment-resistant depression

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.