Ketamine for Depression and Suicide Risk (Ketamine)

Acute and Maintenance Intravenous Ketamine for Treatment Resistant Major Depression With Suicidal Ideation/Attempt

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.

Study Overview

• Status: Completed
• Conditions: Depression; Suicide
• Intervention / Treatment: Drug: Ketamine

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ketamine infusion; This trial was conducted in 2 phases. During the acute-phase, i.v. ketamine was administered thrice-weekly for up to 2 weeks.Those who achieved depressive symptom remission 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.

Drug: Ketamine; 0.3 mg/kg/hr of ketamine infused for 100 minutes; Other Names: Ketalar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MADRS Total Score at Baseline and Last Acute Phase Observation	The Montgomery Asberg Depression Scale (MADRS) is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed). For this study a score of less than or equal to 9 was considered clinical remission of depression.	baseline, last acute phase observation (approximately 2 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MADRS Total Score, Percent Change From Baseline at Last Acute Phase Observation	The Montgomery Asberg Depression Scale (MADRS) is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed). For this study a score of less than or equal to 9 was considered clinical remission of depression.	baseline, last acute phase observation (approximately 2 weeks)
MADRS Factor 1 Score at Baseline and Last Acute Phase Observation	The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. MADRS Factor 1 (Sadness) consisted of MADRS items 1 (Apparent Sadness) and 2 (Reported Sadness). The MADRS Factor 1 Score is derived by adding all the scores from the 2 items, meaning the lowest possible score is 0 and the highest possible is 12.	baseline, last acute phase observation (approximately 2 weeks)
MADRS Factor 1 Score, Percent Change From Baseline at Last Acute Phase Observation	The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. MADRS Factor 1 (Sadness) consisted of MADRS items 1 (Apparent Sadness) and 2 (Reported Sadness). The MADRS Factor 1 Score is derived by adding all the scores from the 2 items, meaning the lowest possible score is 0 and the highest possible is 12.	baseline, last acute phase observation
MADRS Factor 2 Score at Baseline and Last Acute Phase Observation	The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. MADRS Factor 2 (Negative Thoughts) consisted of MADRS items 9 (Pessimistic Thoughts) and 10 (Suicidal Thoughts). The MADRS Factor 2 Score is derived by adding all the scores from the 2 items, meaning the lowest possible score is 0 and the highest possible is 12.	baseline, last acute phase observation (approximately 2 weeks)
MADRS Factor 2 Score, Percentage Change From Baseline at Last Acute Phase Observation	The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. MADRS Factor 2 (negative thoughts) consisted of MADRS items 9 (Pessimistic Thoughts) and 10 (Suicidal Thoughts). The MADRS Factor 2 Score is derived by adding all the scores from the 2 items, meaning the lowest possible score is 0 and the highest possible is 12.	baseline, last acute phase observation (approximately 2 weeks)
MADRS Factor 3 Score at Baseline and Last Acute Phase Observation	The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. MADRS Factor 3 (Detachment) consisted of MADRS items 6 - 8 (Concentration Difficulties, Lassitude, and Inability to Feel). The MADRS Factor 3 Score is derived by adding all the scores from the 3 items, meaning the lowest possible score is 0 and the highest possible is 18.	baseline, last acute phase observation (approximately 2 weeks)
MADRS Factor 3 Score, Percentage Change From Baseline at Last Acute Phase Observation	The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. MADRS Factor 3 (detachment) consisted of MADRS items 6 - 8 (Concentration Difficulties, Lassitude, and Inability to Feel). The MADRS Factor 3 Score is derived by adding all the scores from the 3 items, meaning the lowest possible score is 0 and the highest possible is 18.	baseline, last acute phase observation (approximately 2 weeks)
MADRS Factor 4 Score at Baseline and Last Acute Phase Observation	The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. MADRS Factor 4 (Neurovegetative Symptoms) consisted of MADRS items 3-5 (Inner Tension, Reduced Sleep, and Reduced Appetite). The MADRS Factor 4 Score is derived by adding all the scores from the 3 items, meaning the lowest possible score is 0 and the highest possible is 18.	baseline, last acute phase observation (approximately 2 weeks)
MADRS Factor 4 Score, Percentage Change From Baseline at Last Acute Phase Observation	The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. MADRS Factor 4 (neurovegetative symptoms) consisted of MADRS items 3-5 (Inner Tension, Reduced Sleep, and Reduced Appetite). The MADRS Factor 4 Score is derived by adding all the scores from the 3 items, meaning the lowest possible score is 0 and the highest possible is 18.	baseline, last acute phase observation (approximately 2 weeks)
MADRS Suicide Thoughts (Item 10) Score at Last Acute Phase Observation	The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. Item 10 scores can range from 0 to 6 (with 0 indicating enjoying life, and 6 indicating explicit plans for suicide.)	baseline, last acute phase observation (approximately 2 weeks)
MADRS Suicide (Item 10) Score, Percentage Change From Baseline at Last Acute Phase Observation	The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. Item 10 scores can range from 0 to 6 (with 0 indicating enjoying life, and 6 indicating explicit plans for suicide.)	baseline, last acute phase observation (approximately 2 weeks)
Clinical Global Impression-severity Subscale (CGI-S) at Baseline and Last Acute Phase Observation	The Clinical Global Impression Severity Subscale is an observer rated scale that measures illness severity. It has a range of responses from 1 (normal) through to 7 (among the most extremely ill patients).	baseline, last acute phase observation (approximately 2 weeks)
CGI-S Score, Percentage Change From Baseline at Last Acute Phase Observation	The Clinical Global Impression Severity Subscale is an observer rated scale that measures illness severity. It has a range of responses from 1 (normal) through to 7 (among the most extremely ill patients).	baseline, last acute phase observation (approximately 2 weeks)

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: William V Bobo, MD, Consultant - Psychiatry

Publications and helpful links

General Publications

• 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. Erratum In: J Affect Disord. 2018 Aug 15;236:313.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: March 10, 2014
• First Submitted That Met QC Criteria: March 20, 2014
• First Posted (Estimate): March 24, 2014

Study Record Updates

• Last Update Posted (Actual): August 11, 2017
• Last Update Submitted That Met QC Criteria: August 10, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Depression; Bipolar; Unipolar; Suicidal
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Self-Injurious Behavior; Depression; Depressive Disorder; Suicide; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 13-005152

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No