Biomarkers of Fast Acting Therapies in Major Depression

Summary

The drug Ketamine, available in medical practice since the late 1960s, is currently used for inducing general anesthesia or sedation during medical procedures. When given slowly as an injection into a vein, ketamine is shown to produce a very rapid effect on depression and to improve depressive symptoms within hours to days. By studying patients who receive a ketamine IV infusion, as an add-on treatment for depression, investigators may start to understand how changes in the brain or in gene function relate to getting better over a very short period of time. In this study, the investigators will enroll 60 patients currently ill with major depression selected to receive IV ketamine therapy under medical supervision. To study neurobiological changes relating to symptom improvement, the investigators will use advanced brain scans to measure brain structure, chemistry and function. Blood samples will measure changes in gene regulation and immune system response. Although some people have a rapid antidepressant response to ketamine, others do not respond. Also, antidepressant effects after ketamine usually wear off within days to weeks. We will determine if up to four doses of ketamine delivered two to three times a week may prolong antidepressant response to ketamine therapy. To determine the durability of ketamine treatment for depression, patients will be monitored by phone and via electronic devices twice a week for up to five weeks and will return for a final assessment when their symptoms return. For this trial, brain and blood sample measurements will occur before and after a patient receives their first ketamine infusion. Patients who do not remit after an initial dose of ketamine, will receive up to three additional ketamine treatments. Mood will be measured 24-hours after each subsequent ketamine infusion and brain and blood measurements be repeated at the time of remission or after the fourth ketamine infusion if remission does not occur. Patients will return for a final brain scan and blood sample when their depressive symptoms return or at five weeks if they continue remission. Investigators will able to see how changes brain measurements, gene regulation and immune response relate to improvements and relapse of depressive symptoms with ketamine IV therapy. The ketamine infusion sessions will occur at a special research unit (CTRC) at UCLA.

Conditions

• Major Depressive Disorder

Interventions

DRUG

Ketamine

Approved FDA indications for ketamine include use as an adjunct in the induction and maintenance of general anesthesia and for procedural sedation. For general anesthesia, ketamine is given at dosages ranging from 1-2mg/kg and given either as bolus injection or run continuously (0.1 to 0.3mg/kg/min) in conjunction with another anesthetic or sedation agent. In this study, ketamine at a subanesthetic dose of 0.5mg/kg will be diluted in 60cc of normal saline and administered via a slow IV infusion over 40 minutes at each treatment session in patients while undergoing hemodynamic monitoring. When used in this manner, ketamine infusion does not induce general anesthesia or states of unconsciousness, and patients remain fully awake, responsive to commands, and do not lose respiratory drive.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH)

  collaborator NIH

• University of California, Los Angeles

  lead OTHER

Principal Investigators

• Katherine Narr, Ph.D. · Geffen School of Medicine, University of California, Los Angeles (UCLA)

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

64 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-06-30

Primary Completion

2019-08-31

Completion

2019-08-31

Countries

• United States

Study Locations