Clinical trial NCT02094898: Ketamine for Depression and Suicide Risk
Official title: Acute and Maintenance Intravenous Ketamine for Treatment Resistant Major Depression With Suicidal Ideation/Attempt
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Depression
Suicide
Keywords: Depression
Unipolar
Bipolar
Suicidal
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2014-03-24
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this research study was to find out if the medication known as ketamine could help the symptoms of depression. This drug is approved by the U.S. Food and Drug Administration (FDA) as an anesthetic agent; however, it is not approved for use in depression treatment. The FDA allowed the use of this drug in this research study.

Detailed description: This was a single-arm, open-label trial conducted in two phases. During the acute-phase, i.v. ketamine was administered thrice-weekly for up to 2 weeks.Those who achieved depressive symptom remission (Montgomery Åsberg Depression Rating Scale (MÅDRS)) total score less than or equal to 9 measured 24h after any acute-phase infusion) received continuation-phase treatment that consisted of once-weekly i.v. ketamine infusions for 4 additional weeks. Remission could occur after any of the 6 acute-phase infusions, at which point the next infusion was the first (of four) continuation-phase infusions. Individuals who remitted during acute-phase and completed continuation-phase treatment had 4 additional weekly post-continuation follow-up visits.Those who responded to i.v. ketamine (less than or equal to 50% reduction from baseline in MÅDRS total score) but did not remit during acute-phase were not eligible for continuation-phase treatment. Suicidal ideation was assessed clinically throughout the trial, supplemented by scores on the MÅDRS suicide item.

Eligibility criteria: Inclusion Criteria:

* Current psychiatric hospital inpatient at Mayo Clinic at time of initiation of treatment.
* Ability to provide informed consent
* Male/Female
* Age 18-65 yrs.
* Major Depressive Disorder or Bipolar Disorder I or Bipolar Disorder II with Patient Health Questionnaire-9 (PHQ 9) score ≥15 at hospital assessment
* Treatment resistant depression (TRD) as defined by at least two previous antidepressant or mood stabilizing treatments for depression in adequate dose for 8 weeks
* Patient reported overall suicide risk score ≥3 on the Suicide Status Form (SSF II-R) or score of ≥1on Item 9 of PHQ-9 (all at admission assessment)
* Ability to pass comprehension assessment test related to effects of ketamine and trial objectives and criteria
* Voluntary admission

Exclusion Criteria:

* Diagnosis of schizophrenia, schizoaffective disorder, or active psychosis
* Index episode of depression greater than 2 years
* Ongoing prescription of ≥4 mg lorazepam equivalents total daily or a.m. dosing of any benzodiazepine at time of assessment
* Currently undergoing electroconvulsive therapy, deep brain stimulation or transcranial magnetic stimulation as acute series or for maintenance
* Any active or unstable medical condition as judged by principal investigator
* Previous use or abuse of methamphetamine, cocaine, stimulants (prescribed and illicit) within past 12 months
* Any current abuse or dependence of alcohol or drugs (except nicotine) and abuse or dependence of drugs and alcohol only in full remission (\> 1 month, \< 12 months). Patients will be allowed to enroll if their drug and alcohol abuse / dependence is in full (complete, not partial) sustained (\> 1 year) remission.
* History of traumatic brain injury
* Developmental delay and intellectual disorder
* Encephalopathy (clinical diagnosis within prior 12 months of delirium)
* Cognitive disorder (mild and major)
* Previous participation in earlier Ketamine trial
* Pregnancy
* Prisoners
* Involuntarily hospitalized

Primary outcomes:
measure: MADRS Total Score at Baseline and Last Acute Phase Observation
timeFrame: baseline, last acute phase observation (approximately 2 weeks)
Secondary outcomes:
measure: MADRS Total Score, Percent Change From Baseline at Last Acute Phase Observation
timeFrame: baseline, last acute phase observation (approximately 2 weeks)
measure: MADRS Factor 1 Score at Baseline and Last Acute Phase Observation
timeFrame: baseline, last acute phase observation (approximately 2 weeks)
measure: MADRS Factor 1 Score, Percent Change From Baseline at Last Acute Phase Observation
timeFrame: baseline, last acute phase observation
measure: MADRS Factor 2 Score at Baseline and Last Acute Phase Observation
timeFrame: baseline, last acute phase observation (approximately 2 weeks)
measure: MADRS Factor 2 Score, Percentage Change From Baseline at Last Acute Phase Observation
timeFrame: baseline, last acute phase observation (approximately 2 weeks)
measure: MADRS Factor 3 Score at Baseline and Last Acute Phase Observation
timeFrame: baseline, last acute phase observation (approximately 2 weeks)
measure: MADRS Factor 3 Score, Percentage Change From Baseline at Last Acute Phase Observation
timeFrame: baseline, last acute phase observation (approximately 2 weeks)
measure: MADRS Factor 4 Score at Baseline and Last Acute Phase Observation
timeFrame: baseline, last acute phase observation (approximately 2 weeks)
measure: MADRS Factor 4 Score, Percentage Change From Baseline at Last Acute Phase Observation
timeFrame: baseline, last acute phase observation (approximately 2 weeks)
measure: MADRS Suicide Thoughts (Item 10) Score at Last Acute Phase Observation
timeFrame: baseline, last acute phase observation (approximately 2 weeks)
measure: MADRS Suicide (Item 10) Score, Percentage Change From Baseline at Last Acute Phase Observation
timeFrame: baseline, last acute phase observation (approximately 2 weeks)
measure: Clinical Global Impression-severity Subscale (CGI-S) at Baseline and Last Acute Phase Observation
timeFrame: baseline, last acute phase observation (approximately 2 weeks)
measure: CGI-S Score, Percentage Change From Baseline at Last Acute Phase Observation
timeFrame: baseline, last acute phase observation (approximately 2 weeks)
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Consultant - Psychiatry
name: William V Bobo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vande Voort JL, Morgan RJ, Kung S, Rasmussen KG, Rico J, Palmer BA, Schak KM, Tye SJ, Ritter MJ, Frye MA, Bobo WV. Continuation phase intravenous ketamine in adults with treatment-resistant depression. J Affect Disord. 2016 Dec;206:300-304. doi: 10.1016/j.jad.2016.09.008. Epub 2016 Sep 12.