Hypersomnia as a predictor of response to intravenous ketamine/intranasal esketamine in treatment resistant depression.

Summary

Sleep disturbances affect 94% of patients with treatment-resistant depression, with middle and early insomnia being the most common. Patients who experience hypersomnia (excessive sleep) before treatment show higher response rates and greater improvement in depressive symptoms after receiving intravenous ketamine or intranasal esketamine. Additionally, 15% of patients have an atypical depression phenotype, and most of them also achieve a positive response with greater symptom reduction. A trend toward faster response is seen in both the hypersomnia and atypical depression groups. These sleep-related features may help predict which patients will benefit from ketamine-based treatments.

Study at a glance

Abstract

BACKGROUND Sleep disturbances are highly prevalent in depressive episodes and are linked to higher mood severity and suicidal behaviors. Slow wave sleep (SWS) and REM sleep are compromised in depression. Current evidence suggests that rapid antidepressant effects of intravenous (IV) ketamine in patients with treatment-resistant depression (TRD) is mediated by its effects on SWS and REM sleep. Sleep phenotypes may help predict ketamine response. METHOD In this observational study, we investigated differences in rates of response among sleep phenotypes defined by QIDS-SR in a cohort of patients with TRD (n = 52) treated with IV ketamine or intranasal (IN) esketamine. Also, we explored an atypical depression phenotype and its association between response and change in QIDS-SR following the treatment with IV ketamine/IN esketamine. RESULTS 94 % of patients reported sleep difficulties and 62 % reported more than one sleep phenotype with middle and early insomnia being the most prevalent. Individuals with baseline hypersomnia showed higher response rates and more pronounced improvements on their QIDS-SR score. Additionally, 15 % of patients presented with an atypical depression phenotype; the majority of whom achieved response and had higher reductions on QIDS-SR. A trend towards faster response was identified for hypersomnia and atypical depression phenotypes. LIMITATIONS Observational study design and lack of a placebo group. CONCLUSIONS Our data indicate that patients with TRD who have baseline hypersomnia and atypical depression features experienced a more substantial reduction in depressive symptoms and are more likely to achieve response with ketamine/esketamine. This could serve as a future predictor for clinical response.