Patient-reported Outcomes on Sleep Quality and Circadian Rhythm During Treatment with Intravenous Ketamine for Treatment-resistant Depression

Background: Intravenous (IV) ketamine is a rapid acting antidepressant used primarily for treatment-resistant depression (TRD). It has been suggested that IV ketamine's rapid antidepressant effects may be partially mediated improved sleep and changes to the circadian rhythm.

Objectives: This study explores IV ketamine's association with changes in patient-reported sleep quality and circadian rhythm in an adult population with TRD.

Methods: Adult patients (18-64 years) with TRD scheduled for IV ketamine treatment were recruited to complete patient rated outcomes measures on sleep quality using the Pittsburgh Sleep Quality Index (PSQI) and circadian rhythm using the Morningness-Eveningness Questionnaire (MEQ). Over a 4-week course of eight ketamine infusions, reports were obtained at baseline (T0), prior to second treatment (T1), prior to fifth treatment (T2), and 1 week after eighth treatment (T3).

Results: Forty participants with TRD (mean age = 42.8, 45% male) were enrolled. Twenty-nine (72.5%) had complete follow-up data. Paired tests revealed statistically significant improvements at the end of treatment in sleep quality (PSQI) ( = 0.003) and depressive symptoms (Clinically Useful Depression Outcome Scale-Depression,  < 0.001) while circadian rhythm (MEQ) shifted earlier ( = 0.007). The PSQI subscale components of sleep duration ( = 0.008) and daytime dysfunction ( = 0.001) also improved. In an exploratory analysis, ketamine's impact on sleep quality was more prominent in patients with mixed features, while its chronobiotic effect was prominent in those without mixed features.

Conclusion: IV ketamine may improve sleep quality and advance circadian rhythm in individuals with TRD. Effects may differ in individuals with mixed features of depression as compared to those without. Since this was a small uncontrolled study, future research is warranted.