Residual Depressive Symptoms in Treatment-Resistant Bipolar Depression Following Short-Term Ketamine Administration.

After a course of ketamine infusions, many patients with bipolar depression still experience residual symptoms, even when their overall depression scores improve. In a real-world analysis of 22 patients receiving ketamine while continuing their usual medications, 14 responded to treatment. The most common lingering symptoms were sad mood (85.7% of responders), a pessimistic view of the future (78.6%), difficulty falling asleep, and low physical energy (both 71.4%). Difficulty falling asleep and sad mood were also rated as the most severe. These findings highlight that functional recovery may require targeting specific residual symptoms beyond overall mood improvement.

Study at a glance

Abstract

Residual symptoms are frequently observed in a significant number of patients with depression, indicating an unmet need for effective management strategies to achieve functional recovery. This observational study aimed to evaluate the impact of ketamine infusions on depressive symptoms in patients with bipolar disorder who continued their baseline psychotropic and chronic somatic treatments. Datasets of the two consecutive real-world registries (NCT04226963 for 2019-2022; NCT05565352 from 2023 onward) for the tertiary reference center for psychiatry at the Medical University of Gdańsk (Poland) for the safety and tolerability of ketamine use in mood and anxiety disorders were retrospectively analyzed. Depressive symptoms were assessed using the Inventory of Depressive Symptomatology Self-Report 30 (IDS-SR30). Residual symptoms were identified in patients who achieved a treatment response, defined as a 50% or greater reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline to the seventh infusion. Overall, 14 out of 22 patients met the criteria for response. The most commonly persistent depressive symptoms included sad mood (85.7%), view of my future (78.6%), difficulty falling asleep, and leaden paralysis/physical energy (both 71.4%), with the most severe being difficulty falling asleep (64.3%) and sad mood (42.9%). This observational post hoc analysis indicates that the most frequently observed residual depressive symptoms were low mood, altered view of future, sleep disturbances, and low energy levels. This study should be treated with caution as causality does not apply, however, it reports on a real-world population of subjects with treatment-resistant bipolar depression. Establishing standardized definitions for residual symptoms could enhance the quality and comparability of future research in this area.