Biomarkers of Fast Acting Therapies in Major Depression

• Status: Completed
• Trial end date: 2019-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, Los Angeles
• Collaborator: National Institute of Mental Health (NIMH)
• Treatments: Ketamine

Criteria

Inclusion Criteria:

• Age between 18 to 64 years, inclusive

• Diagnosis: DSM-IV TR criteria for non-psychotic major depression

• Hamilton Depression Rating Scale-17 item ≥ 18 or Montgomery Asberg Depression Scale ≥ 20

• A history of at least one previous major depressive episode prior to the current episode

• Recurrent Depression - in the current episode, have not responded to at least 2 adequate antidepressant trials (using Antidepressant Treatment History Form criteria)

• Have been continuously depressed for between 6-12 months

• Receiving approved monoaminergic antidepressant therapy

• No changes in antidepressant medication(s) in the past one (1) month

• Voluntary patient receiving ketamine

• Capacity to provide informed consent

• Have no contraindications to an adjunctive trial of ketamine infusion

• Be under the current care of a treating Psychiatrist

• If outpatient, a responsible driver available for transportation to and from scanning sessions

• Live locally, within travelling distance to UCLA

• Be available to participate for a 5-week research follow-up

Exclusion Criteria:

• Younger than 18 or older than 64

• Serious and imminent suicidal or homicidal risk (active suicidal ideations with or without a plan, HAM-D score ≥ 3 on item 3)

• Mental retardation or other developmental disorder

• Diagnosis of dementia of any type

• History of current substance abuse or dependence

• Psychotic reactions to medications, alcohol or illicit substances in the past

• Current or past history of psychosis, schizophrenia, bipolar disorder, delusional disorder or other psychotic disorder

• Treatment with medications with NMDA and NMDAR action

• Contraindication to ketamine

• Depression related to serious medical illness (i.e., mood disorder due to general medical condition)

• History of neurological disorder or other physical disorder (i.e. significant head injury) that could affect brain functioning

• Serious or unstable medical or neurological condition(s) that in the opinion of the treating physician or PI renders ketamine unsafe to administer

• Any condition that would contraindicate scanning (metal implants, claustrophobia or a breathing or movement disorder)

• Pregnancy (as confirmed by positive urine pregnancy test) or planning on becoming pregnant

• Non-English speaking (due to scales administered)

• Live outside of the Los Angeles area