Endogenous opioid modulation by ketamine

Principal Investigator: Brian Mickey
Keywords: Major Depressive Disorder , Rapid Antidepressant , Tissue Banking , MRI , Pain Testing , PET Department: Psychiatry
IRB Number: 00087544 Co Investigator: Jon-Kar Zubieta
Specialty: Psychiatry
Sub Specialties:
Recruitment Status: Not yet recruiting

Contact Information

Anna Hartvigsen
anna.arp@hsc.utah.edu
801-585-9450

Brief Summary

This study will test the hypothesis that the rapidly-acting antidepressant ketamine improves core depressive symptoms by acutely activating the brain's endogenous µ-opioid system.

Aim 1:  Demonstrate the acute effects of ketamine on endogenous µ-opioid neurotransmission in humans.

Aim 2:  Determine the extent to which individual differences in ketamine-induced µ-opioid system activation are associated with changes in core depressive symptoms.

Aim 3 (exploratory):  Discover brain connectivity and peripheral gene expression features at baseline that predict differential response to ketamine.

Inclusion Criteria

We will enroll forty (40) adults, age 18–65, with a current moderate-to-severe depressive episode, defined as PHQ-9 total ≥ 10 (including item scores ≥ 2 on "Little interest or pleasure" and "Feeling down, depressed, or hopeless" items) and medical documentation of depression for at least 2 months. A diagnosis of DSM-IV/DSM-5 major depressive disorder will be confirmed using the MINI structured interview (Sheehan et al., 1998) and review of medical records. Unless contraindicated with Ketamine, stable doses of concomitant non-opioid, non-sedative medications will be permitted but are not necessary for participation. Additional therapies will not be provided to participants.

Exclusion Criteria

Individuals with chronic depression (current episode duration >2 years) or high medication resistance (non-response to >3 adequate trials in the current episode, established with the Antidepressant Treatment History Form (Sackeim, 2001)) will be excluded because these individuals are less responsive to antidepressant therapies in general. To avoid potential confounding effects of comorbid DSM-5 diagnoses, we will exclude current (past year) moderate-to-severe substance use disorder, cognitive disorder, PTSD, OCD, or personality disorder.  For safety reasons, we will also exclude participants with a positive urine drug screen or a history of psychotic symptoms, mania, significant neurologic disorder or injury, breastfeeding, pregnancy, imminent suicide risk, contraindication to ketamine, or other unstable psychiatric or medical condition requiring a higher level of care.