Slow Wave Induction by Propofol to Eliminate Depression (SWIPED): Phase I

Ben Palanca, MD, PhD, MSc, Associate Professor, Anesthesiology

Late life treatment-resistant depression (LL-TRD) in older adults is a leading cause of disability, excess mortality from suicide, and dementia. Cognitive problems and sleep disturbances are common, contributing to recurrence and poor long-term outcomes. Disrupted slow wave sleep is at the nexus of depression and cognitive dysfunction in older adults. Novel approaches to target this core pathophysiology are lacking. Our mechanistic project, Slow Wave Induction by Propofol to Eliminate Depression(SWIPED) Trial: A Pilot Study, is designed to elucidate the relationships between TRD, sleep disturbances, and cognitive impairments in older adults. Through personalized infusions targeting electroencephalographic (EEG) patterns, we aim for a systematic characterization of the relationships between the propofol-induced EEG slow waves, enhancement of slow wave sleep, and cognitive outcomes. Through the repurposing of propofol as a therapeutic probe, this innovative proposal will establish whether EEG slow waves are a viable therapeutic target for novel antidepressant approaches. We will enroll 15 individuals to receive a dose-finding propofol infusion, and then a second infusion at the dose determined to induce slow waves. This phase will establish that propofol both induces slow waves during the infusion and enhances slow wave sleep (SWS) on nights of sleep post-infusion. This work will lay the groundwork for a future randomized control trial aimed at enhancing our understanding of core deficits contributing to poor mood and cognition in a population at risk for Alzheimer’s disease and related dementias. With the rise in the aging population, we hope to provide translatable biomarkers and approaches for future precision medicine, with a long-term goal of improving public health and quality of life for those afflicted with TRD.