Ketamine for Depression and Suicide Risk

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Depression, Suicide

Intervention / Treatment
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* Drug: Ketamine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine infusion<br>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<br>* 0.3 mg/kg/hr of ketamine infused for 100 minutes<br>* Other names: Ketalar;|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Unipolar, Bipolar, Suicidal