slow wave induction by propofol to eliminate depression (swiped) i

Conditions: Treatment-resistant Depression

Summary: our hypothesis is that targeted propofol infusion in treatment-resistant depressed patients will induce slow wave activity during sedation and augment subsequent sleep slow wave activity. we will recruit 15 participants for this open label single arm phase i trial. all participants will undergo two propofol infusions 2-6 days apart, with each infusion maximizing expression of eeg slow waves. to minimize bias, there will be no specific gender or ethnic background consideration for enrollment. this will be a single site investigation at washington university medical center.

treatment-resistant depression (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 is designed to elucidate the relationships between trd and sleep disturbances 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 and enhancement of slow wave sleep. 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. study intervention propofol will be infused through a peripheral iv, with the assistance of target-controlled infusion software and pumps, with an anticipated infusion duration of 1-2 hours. concurrent high-density eeg will be acquired, but with an updated recording rig and sensor nets that use either elefix conductive gel or salt solution. an axis p3364lv network camera, synchronized to eeg recordings, will provide video for post-hoc analysis. participants will be discharged home after nurse monitoring and fulfillment of post-anesthetic care unit criteria. patients will be instructed by staff on operation of the dreem headband for at-home overnight sleep eeg recordings. patients will demonstrate ability to successfully wear the dreem and initiate recordings without assistance. the device, charger, instruction sheet, and a link to a 2-minute instructional video will be provided to patients. this paradigm has been successful in the acquisition of preoperative sleep recordings in over 150 geriatric cardiac surgical patients and eight patients who underwent ect for trd (clinicaltrials.gov nct04451135). dreem recordings will be obtained prior to the first propofol infusion and on evenings of propofol infusions. additionally, recordings will be obtained for up to 6 nights within a 2-week period after the final infusion, to evaluate persistence of restoration of sleep architecture. participants will exchange the device with staff during each in-person visit, to allow device examination and data download. planned subgroup analyses include stratification by sex and age. for the purposes of phase ii of the study, additional subgroup analyses will be performed based on baseline sleep structure (e.g. total sleep time and proportion of time in n3 sleep), and time interval separating the two infusions.

Eligibility criteria:
inclusion criteria: * provision of signed and dated informed consent form * stated willingness to comply with all study procedures and availability for the duration of the study * age 60 or greater * english speaking (as an interpreter will not be readily available should a participant need to convey any safety concerns during the propofol infusion sessions or require guidance on conducting at-home sleep recordings) * treatment-resistant depression (non-responsive to at least two adequate trials of oral antidepressants for current episode). exclusion criteria: * presence of symptomatic coronary artery disease * presence of marked congestive heart failure/cardiomyopathy (nyha \> class iii, lvef \<40%, greater than mild rv systolic dysfunction) * prior reaction to propofol * resting heart rate \< 50 bpm * treatment with electroconvulsive therapy/transcranial magnetic stimulation/vagal nerve stimulation within 6 weeks * body mass index \> 35 * c-ssrs of 4 or greater (active suicidal ideation with some intent and with/without a specific plan) * moca score \< 23 (at least mild dementia) * non-prescribed used of amphetamines, opioids, marijuana, cocaine, or phencyclidine * intake of \> 14 beers/week (or equivalent) * anesthetic exposure in the past 4 weeks * concurrent use of benzodiazepines \> 2 mg/day lorazepam or equivalent, trazodone \> 50 mg/day, or gabapentin \> 600 mg/day.