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

Inclusion Criteria:

1. Meeting the case-definition for PASC with depressive symptoms
2. Otherwise physically healthy
3. No adverse reactions to study medications
4. Capacity to consent and comply with study procedures, including sufficient proficiency in English
5. Sexually active participants must use an effective form of birth control (condom plus spermicide, diaphragm plus spermicide, or birth control pills) before and throughout their study participation.
6. Willingness to provide one or more emergency contacts to the study team

Exclusion Criteria:

1. Meeting the DSM-5 criteria for lifetime history of bipolar disorder, schizophrenia, or any psychotic illness.
2. Lifetime history of delirium, dementia, amnesia, or dissociative disorders
3. Current suicide risk or a history of suicide attempt within the past year
4. Pregnant or interested in becoming pregnant during the study period.
5. Any of the following cardiac conditions: clinically significant left ventricular hypertrophy, angina, clinically significant arrhythmia within 1 year of signing study consent form.
6. Unstable physical disorders which might make participation hazardous such as hypertension (\>160/90), anemia, active hepatitis or other liver disease (transaminase levels \<3 X the upper limit of normal will be considered acceptable), epilepsy, or untreated diabetes. Participants reporting HIV+ status will be asked to provide information about their current treatment, including all medications. Participants who are on the antiretroviral ritonavir (Norvir) will be excluded due to the possibility that ketamine in combination with this medication may increase the risk of drug-induced hepatitis.
7. Previous history of a substance use disorder with the study medications, and/or a history of an adverse reaction/experience with prior exposure to the study medications.
8. Recent history of significant violence (past 2 years) leading to an individual incurring physical harm, police involvement, or resulting in legal action.
9. On psychotropic or other medications whose effect could be disrupted by participation in the study.
10. Other personal circumstances and behavior judged to be incompatible with establishment of rapport or safe exposure to the study medications.
11. Physiologic dependence on a substance including benzodiazepines, alcohol, or opioids.