FC33: Hilarious Gas for treatment resistant depression in older adults: is it really serious?

Nitrous oxide (N2O) shows promise as a fast-acting antidepressant for treatment-resistant depression (TRD), especially in older adults. Its mechanisms may include NMDA receptor antagonism and cerebral vasodilation, which could improve drug delivery and address resistance linked to poor cerebrovascular function. N2O is not metabolized by the kidney or liver, potentially making it safer for older adults. Review of available data on efficacy, safety, and pathophysiology is presented, along with results showing reduced anterior cingulate cortex connectivity and increased brain tissue pulsations during successful N2O treatment. Ongoing RCTs in older adults with TRD and neurocognitive disorders are discussed.

Study at a glance

Abstract

Nitrous oxide (N2O – also known as Hilarious Gas) has recently emerged has a potential fast-acting antidepressant, based on a number of randomized controlled trials (RCT) in young adults with treatment resistant depression (TRD). The antidepressant mechanisms of N2O are not fully understood but may include an antagonist action on NDMA receptors, similar to ketamine. N2O shows additional cerebral effects that may be particularly appropriate for TRD in older adults, including a significant cerebral vasodilatation that facilitates blood brain barrier opening and potentially limits resistance related to poor cerebrovascular functioning. Moreover, N2O may prove to be particularly well-tolerated in this potentially fragile population, notably because it is not metabolized by the kidney or liver which organs may be impaired with aging.In this talk, we will be reviewing the available data on the efficacy, safety and pathophysiology of N2O, with a specific focus on older adults. We will also present results from our group showing a significant reduction in cerebral connectivity in the anterior cingulate cortex (ACC - as measured with pre and post treatment resting state MRI) and large increase in brain tissue pulsations (as measured with Ultrasound) with a successful treatment with N2O compounds. Finally, perspectives on current studies in older adults from our group (one RCT in non-demented older adults with TRD and one RCT in neurocognitive disorders) will be discussed.Figure 1Changes in ACC connectivity after exposure to N2O compoundsFigure 1Changes Brain Tissue Pulsations as assessed with brain ultrasound during N2O exposure