Ketamine Associated ACC GABA and Glutamate Change and Depression Remission


About this study

This feasibility study aims to better understand the neurobiology of major depression and how ketamine may therapeutically impact brain function. This research may provide important insights into the mechanism of ketamine response, thus, potentially increasing the likelihood of successful treatment interventions and decrease the number of ineffective treatments and/or risk for serious side effects.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Ability to provide informed consent.
  • Current psychiatric inpatient (voluntary only) or outpatient treatment.
  • Male or female.
  • Age 18-65 years.
  • Meets diagnostic criteria for major depressive disorder or bipolar depression without psychotic features per the SCID DSM-IV-TR.
  • PHQ-9 total score ≥ 15 at screening and at baseline (just prior to first acute phase ketamine infusion).
  • Treatment-resistant depression, as defined by failure of at least two previous antidepressant treatments within the current depressive episode.  Failed antidepressant treatments can include pharmacotherapy for depression at an adequate dose for at least 8 weeks, or an acute series of at least 6 administrations of electroconvulsive therapy (ECT).
  • Ability to pass a comprehension assessment test related to effects of ketamine and trial objectives and criteria.

Exclusion Criteria:

  • Inability to speak English.
  • Patients with a BMI > 40.
  • Any current psychiatric diagnosis other than anxiety disorders needing concurrent antidepressant therapy.
  • Personality disorder being the primary diagnosi.s
  • Diagnosis of schizophrenia, schizoaffective disorder, post-traumatic stress disorder, or active psychotic symptoms.
  • Ongoing prescription of > 4 mg lorazepam equivalents (total) daily, or morning dosing of any benzodiazepine at the time of assessment;
  • Medications known to affect glutamate (i.e., Riluzole, Carbamazepine) or GABA (zaleplon, zolpidem, zopiclone, Valproate, Gabapentin, Pregabalin, tiagabine, and vigabatrin) are prohibited within two weeks prior to administration of study drug.
  • Antidepressant Monoamine Oxidase Inhibitors (MAOIs) are prohibited two weeks prior to administration of study drug.
  • CYP3A4 inducers carbamazepine and modafinil are prohibited within two weeks prior to administration of study drug and at least 24 hours after last dose of study drug.
  • Currently undergoing transcranial magnetic stimulation, vagal nerve stimulation, or deep brain stimulation as either an acute or maintenance treatment of depression.
  • ECT in the past 12 months.
  • Any active or unstable medical condition judged by the study psychiatrist as conferring too great a level of medical risk to allow inclusion in the study.
  • Use of methamphetamine, cocaine, or cannabis. Abuse of stimulant(s) within the prior 12 months.
  • Any current substance use disorder (excluding nicotine and caffeine). 
    • Note:  Persons will be allowed to enroll in this study if their substance use is in complete (not partial) and sustained (> 1 year) remission.
  • History of traumatic brain injury that resulted in loss of consciousness;
  • Developmental delay, intellectual disability, or intellectual disorder.
  • Clinical or self-reported diagnosis of delirium, encephalopathy, or related clinical diagnosis within the prior 12 months.
  • Cognitive disorder (mild and major categories, per DSM-).
  • Received ketamine treatment for depression within the prior 2 months.
  • History of either poor antidepressive response to or poor tolerability of ketamine (any route of administration) when previously administered for treating symptoms of depression.
  • History of hypothyroidism unless taking a stable dose of thyroid medication and asymptomatic for 6 months.
  • Hepatic insufficiency (2.5 X ULN for AST or ALT) within 1 year of consent, past liver transplant recipient, and/or clinical diagnosis of cirrhosis of the liver.
  • Gastroesophageal reflux disease
  • A diagnosis of Complex Regional Pain Syndrome (CRPS).
  • Pregnancy, or nursing.
  • History of claustrophobia.
  • Any contraindication to MRI safety questionnaire.

Eligibility last updated 4/20/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Balwinder Singh, M.D.

Closed-enrolling by invitation

What is this? (?)
Not open to everyone who meets the eligibility criteria, but only those invited to participate by the study team.

Contact information:

Jose Rico M.B.A.

(507) 255-9352

More information


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