2026 ECNP Congress

PS04-4129

Ketamine effects on life engagement in treatment-resistant unipolar and bipolar depression: post hoc analysis of Inventory of Depressive Symptomatology Self-Report

Zofia Kachlik — M. Walaszek, K. Pastuszak, W.J. Cubała · Medical University of Gdańsk, Department of Psychiatry, Gdańsk, Poland

2026 ECNP Congress

Introduction

Treatment-resistant depression (TRD) and treatment-resistant bipolar depression (TRBD) are both associated with poor outcomes and insufficient response to conventional therapies[1,2]. Rapid-acting antidepressants such as ketamine have enhanced symptom relief, but increasing attention is being paid to broader dimensions of treatment response. Patient-reported outcomes can capture domains that are clinically important to patients yet often neglected by clinician-centred scales. Life engagement represents one such domain, reflecting life fulfilment, well-being, and participation in valued and meaningful activities[3].

Aims

This analysis investigated the effects of ketamine adjunct to antidepressant treatment on patient life engagement over the short term, using the 10-item Inventory of Depressive Symptomatology Self-Report Life Engagement subscale (IDS-SR 10 LE).

Methods

A retrospective analysis using data from naturalistic, observational registries including 65 inpatients, 34 with TRD and 31 with TRBD (NCT04226963 and NCT05565352). Treatment resistance was defined as a clinically unsatisfactory response following at least two adequate lines of treatment in terms of dose and duration. Patients received short-term ketamine (intravenous: 0.5 mg/kg; oral: 2.0–2.5 mg/kg) as add-on intervention over four weeks with a subsequent 7-day long follow-up. Life engagement-related outcomes were assessed using the IDS-SR 10 LE subscale prior to the first, third, and seventh ketamine administration. The IDS-SR 10 LE subscale composed of the following ten items from IDS-SR scale: response of your mood to good or desired events, concentration/decision making, view of myself, view of my future, general interest, energy level, capacity for pleasure or enjoyment (excluding sex), interest in sex, feeling slowed down, and interpersonal sensitivity[4]. Binary variables were analyzed using Fisher’s exact test. For categorical variables with more than two levels, Fisher’s exact test with the Freeman-Halton extension was applied. Groups were compared to sociodemographic and clinical variables. For statistical analysis, the normality of quantitative variables was assessed using the Shapiro-Wilk test. For normally distributed variables, comparisons were made using the t-test. Within-group change from baseline was tested using one-sample t tests when change scores were normally distributed and Wilcoxon signed-rank tests otherwise. A p-value of 0.05 was considered statistically significant.

Results

Over 4 weeks, patients with TRD and TRBD showed significant improvement in IDS-SR 10 LE scores. In the TRD group, the mean change was −5.12 (95% CI: −8.12, −2.10; p = 0.0101). In the TRBD group, the mean change was −5.81 (95% CI: −8.66, −2.95; p < 0.001). Although patients with TRBD showed a numerically greater improvement than those with TRD prior to the third ketamine administration (mean scores: 12.7 [95% CI: 9.93, 15.6] vs. 15.5 [95% CI: 13.3, 17.6]), this difference did not reach statistical significance (p = 0.123).

Conclusions

Adjunctive ketamine was associated with significant short-term improvements in life engagement in both TRD and TRBD. These effects appeared clinically meaningful and were comparable across diagnoses, suggesting benefits beyond core depressive symptoms in domains valued by patients. Life engagement represents a relevant patient-centred outcome and warrants further investigation in larger, prospective studies.

References

  1. McIntyre RS, Alsuwaidan M, Baune BT, Berk M, Demyttenaere K, Goldberg JF, et al. Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions. World Psychiatry 2023;22:394–412. https://doi.org/10.1002/wps.21120.
  2. Vieta E, McIntyre RS, Suppes T, Van Rheenen TE, Singh B, Miskowiak KW, et al. Defining Treatment‐Resistant Bipolar Depression: Recommendations From the ISBD Task Force. Bipolar Disord 2025;27:411–23. https://doi.org/10.1111/bdi.70048.
  3. McIntyre RS, Ismail Z, Watling CP, Weiss C, Meehan SR, Musingarimi P, et al. Patient-reported outcome measures for life engagement in mental health: a systematic review. J Patient Rep Outcomes 2022;6:62. https://doi.org/10.1186/s41687-022-00468-5.
  4. Thase ME, Ismail Z, Meehan SR, Weiss C, Regnier SA, Larsen KG, et al. Assessment of patient life engagement in major depressive disorder using items from the Inventory of Depressive Symptomatology Self-Report (IDS-SR). J Psychiatr Res 2023;161:132–9. https://doi.org/10.1016/j.jpsychires.2023.02.008.