Glutamatergic Modulation as a Treatment for Depressive Symptoms Among Patients With Post-acute Sequelae of COVID (PASC): A Pilot Trial

While PASC symptoms have been identified in nearly every organ system, the most common symptoms include fatigue, cognitive and attention deficits (known as 'brain fog'), shortness of breath, and post-exertional malaise. New-onset depression, anxiety, and even suicidal behavior have also been reported. Symptoms of PASC can exhibit daily variation; additionally PASC frequently demonstrates a relapsing and remitting course. This is mitigated by cognitive and emotional stress, physical exertion, diet, and alcohol consumption; therefore, measuring treatment response and the course of illness over time can be challenging. While there are many ongoing trials evaluating a variety of treatments for PASC, no clear treatment has emerged; additionally, there are no published data on psychotropic medications alleviating the inflammatory response and psychiatric symptoms in PASC. Alterations in the transmission between neurons of a neurotransmitter called glutamate are an important target of pharmacotherapy for PASC. Glutamate modulators have demonstrated promise in improving depressive symptoms and suicidality and can improve cognitive functioning among patients with these symptoms. The study team has recently developed a novel design that integrates a clinical trial involving serial infusions. The current trial will evaluate the effect of a sub-anesthetic infusion on individuals with PASC and depressive symptoms who complete a randomized, double-blind, placebo-controlled pilot study conducted over 5 weeks using a cross-over and counterbalanced design.