Burst Suppression Anesthesia for Treatment of Sever Depression

Principal Investigator: Brian Mickey
Keywords: Burst suppression , Major Depressive Disorder , Propofol , Treatment Resistant Depression , Deep Anesthesia Department: Psychiatry
IRB Number: 00090838 Co Investigator: Kelly Smith
Specialty: Psychiatry, Anesthesiology
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Andrea White
andrea.white@health.utah.edu
801-587-1288

Brief Summary

Study 1 will test the central hypothesis that high dose isoflurane anesthesia inducing EEG burst suppression (High ISO/BS+) is a more effective intervention for severe depression when compared to a low dose isoflurane anesthesia that does not induce EEG burst suppression (Low ISO/BS-). The proposed study is a randomized, double-blind trial that will evaluate 30 actively depressed patients with moderate to severe depression.  Depression outcomes will be compared between two groups of patients (n=15 per group) who have received 10 treatment applications over a period of three weeks of either High ISO/BS+ or Low ISO/BS- .

Aim 1. To determine whether High ISO/BS+ is more effective than Low ISO/BS- in producing either a treatment response (defined as 50% reduction in depression scores) or full remission of depressive symptoms. We hypothesize that significantly more depressed patients randomized to receive 10 treatments of High ISO/BS+ compared to Low ISO/BS- will show a positive treatment response or full remission by treatment end. Based on the STAR*D Trial 39, a responder is a patient showing 50% reduction in depression score and full remission is defined as a score of 0-10 on the HRSD-24 scale and score of 0-5 on the QIDS-SR16.

Aim 2. Preliminary data on neural and immune pathways that are differentially affected by the 2 treatments and associated with antidepressant effects will be explored by comparing changes from pre-treatment to post-treatment in full transcriptome leukocyte gene expression (using the RNA Seq method).

Aim 3.  To measure the central neurochemical effects of isoflurane treatment, we will quantify neurotransmitter levels (GABA and glutamate) using magnetic resonance spectroscopy.

Pilot Study 2 is designed to complement Study 1 in providing additional support for the hypothesis that burst suppression is an important mechanism for antidepressant treatment effects of anesthesia in moderate to severe depression. If Study 1 demonstrates that more patients receiving High ISO/BS+ undergo remission than those receiving Low ISO/BS-, this could be interpreted as a dose response effect for isoflurane that is not specifically a result of burst suppression. Demonstrating that a different anesthetic administered at doses producing 80% burst suppression for 10 treatment session is also effective in producing depression remission would add support for the hypothesis that the underlying mechanism is burst suppression. Therefore, Study 2 will be an open-label trial to provide preliminary data that propofol, an intravenous anesthetic with a favorable safety profile, administered for 10 treatment sessions at levels to induce 80% burst suppression, also is effective in producing depression remission in 50% or more of the pilot sample of 10 depressed patients.

Aim 4. To determine whether propofol anesthesia at a level to produce 80% EEG burst suppression is effective in producing remission of depressive symptoms. We hypothesize that the majority of depressed patients (n=10) receiving 10 treatments of propofol anesthesia will achieve remission of symptoms by treatment end.

Aim 5. Preliminary data on neural and immune pathways that are differentially affected by the 2 treatments and associated with antidepressant effects will be explored using full transcriptome leukocyte gene expression (RNA Seq).

Aim 6.  To measure the central neurochemical effects of propofol treatment, we will quantify neurotransmitter levels (GABA and glutamate) using magnetic resonance spectroscopy.

Inclusion Criteria

Age: 18-55 years

BMI: < 40

Diagnosis of Major Depressive Disorder (MDD) or Bipolar Disorder (I or II, most recent episode must be depression)

Must have had 2 failed anti-depressant treatments and no ECT in past 6 months

Hamilton Rating Scale for Depression (HSRD) score > 18 AND Quick Inventory of Depression Scale (QIDS) score >10

 

Exclusion Criteria

  • Diagnosis of other current and/or active DSM-5 disorders with the exception of anxiety disorders

  • Significant pre-morbid cognitive impairment

  • Hypertension and current use of ACE inhibitor or AR blocker medications

  • Symptomatic coronary artery disease or congestive heart failure

  • History of transient ischemic or neurologic signs during the past year

  • History of or susceptibility to malignant hyperthermia

  • Contraindication to isoflurane or propofol anesthesia (as determined by anesthesiologist)

  • Diabetes requiring insulin

  • Poor kidney function

  • Chronic use of benzodiazepines or opioids

  • Individuals incompetent to provide consent (e.g. catatonic, psychotic).