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Ketamine Infusion for Adolescent Depression and Anxiety

Primary Purpose

Major Depressive Disorder, Anxiety Disorder

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Ketamine

Midazolam

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring Ketamine, Depression, Major Depressive Disorder, Anxiety, School refusal, Suicide, Generalized Anxiety, Suicidal Ideation

Eligibility Criteria

13 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion:

MDD Cohort:

Meet DSM-5 criteria for Major Depressive Disorder by structured interview (MINI-KID)
CDRS-R score >40.
Failure to achieve remission with at least 1 adequate prior antidepressant trial (e.g. SSRI, SNRI, or TCA), meaning at least 8 weeks at therapeutic dosing, including at least 4 weeks of stable dosing.

Anxiety Cohort:

Meet DSM-5 criteria for any of the following anxiety disorders: Social Anxiety Disorders, Generalized Anxiety Disorder, Separation Anxiety Disorder and/or Panic Disorder by structured interview (MINI-KID)
ADIS Clinical Severity Rating ≥4 (moderately severe) for any of the 4 included anxiety disorders
Failure to achieve remission with at least 1 adequate prior anxiolytic medication trial (e.g. SSRI, SNRI, or TCA), meaning at least 8 weeks at therapeutic dosing, including at least 4 weeks of stable dosing.
Failure to achieve remission with previous CBT or subject declines current CBT therapy

Both cohorts:

Stable psychiatric medications and doses for the month prior to enrollment. Subjects may continue to engage in any ongoing psychotherapy.
Medically and neurologically healthy on the basis of physical examination and medical history.
Parents able to provide written informed consent and adolescents must additionally provide assent.

Exclusion:

Current inpatient hospitalization or active suicidal ideation requiring referral for inpatient hospitalization for safety.
History of psychotic disorder or manic episode diagnosed by MINI-KID
History of substance dependence diagnosis by MINI-KID (excluding tobacco) or positive urine toxicology.
Pregnancy (urine pregnancy tests on the day of scans for menstruating girls).
Inability to provide written informed consent according to the Yale Human Investigation Committee (HIC) guidelines in English.

Sites / Locations

Hospital Research Unit at the Yale New Haven Hospital
Yale Child Study Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Ketamine

Midazolam

Arm Description

Participants were randomly be assigned to receive a dose of 0.5 mg/kg of Ketamine (administered intravenously over 40 minutes with a maximum total dose allowed in this study will be 50mg).

Participants were randomly assigned to receive a dose of 0.045mg/kg of Midazolam (administered Intravenously over 40 minutes with a the maximum total dose allowed in this study of 4.5mg),

Outcomes

Primary Outcome Measures

Montgomery-Asberg Depression Rating Scale Score 1 Day After Infusion

Depressive symptoms (measured by Montgomery-Asberg Depression Rating Scale, revised (MADRS) score) on 1 day after infusion, for the cohort of subjects enrolled in the MDD arm of this trial. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. Usual cutoff points are: 0 to 6 - normal /symptom absent. 7 to 19 - mild depression. 20 to 34 - moderate depression. >34 - severe depression.

Secondary Outcome Measures

Full Information

NCT ID

NCT02579928

First Posted

October 16, 2015

Last Updated

June 29, 2020

Sponsor

Yale University

Collaborators

American Academy of Child Adolescent Psychiatry.

1. Study Identification

Unique Protocol Identification Number

NCT02579928

Brief Title

Ketamine Infusion for Adolescent Depression and Anxiety

Official Title

Efficacy of Rapid-Acting NMDA Antagonist for Treatment of Adolescent Depression and Anxiety Disorders

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Completed

Study Start Date

October 2015 (undefined)

Primary Completion Date

September 28, 2018 (Actual)

Study Completion Date

September 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Yale University

Collaborators

American Academy of Child Adolescent Psychiatry.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to determine the tolerability and short-term efficacy of a single ketamine infusion for the treatment of adolescents with 1) medication-refractory major depressive disorder (MDD) and/or 2) medication-refractory anxiety disorders (social anxiety disorder, panic disorder, generalized anxiety disorder and/or separation anxiety disorder).

Detailed Description

We will conduct a crossover trial in which as many as 36 adolescents (18 with MDD and 18 with anxiety disorders) will be given a single infusion of ketamine (study drug) or midazolam (active control). MDD symptoms and anxiety symptoms will be monitored over a two-week period. If applicable, comorbid school refusal symptoms will also be monitored over a two-week period for both cohorts. A 2-week washout period will be required between infusion doses. Our primary outcomes will be 1) improvement in MDD symptoms (measured by Montgomery-Asberg Depression Rating Scale, revised (MADRS) score) 1 day after infusion, for the cohort of subjects enrolled in the MDD arm of this trial and 2) improvement in the anxiety symptoms (measured by the Multimodal Anxiety Scale for Children (MASC) acute physical symptoms subscale) for the cohort of subjects enrolled in the anxiety disorders arm of the trial.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Major Depressive Disorder, Anxiety Disorder

Keywords

Ketamine, Depression, Major Depressive Disorder, Anxiety, School refusal, Suicide, Generalized Anxiety, Suicidal Ideation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Model Description

Participants were randomly assigned the treatment order, with participants receiving a single infusion of either ketamine hydrochloride (0.5 mg/kg) or midazolam (0.045 mg/kg) on Day 1, and the alternate compound 2 weeks later.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Midazolam was chosen as an active placebo in keeping with its similar pharmacokinetic profile and precedent as a reasonable comparator for nonspecific behavioral effects of ketamine

Allocation

Randomized

Enrollment

17 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ketamine

Arm Type

Experimental

Arm Description

Participants were randomly be assigned to receive a dose of 0.5 mg/kg of Ketamine (administered intravenously over 40 minutes with a maximum total dose allowed in this study will be 50mg).

Arm Title

Midazolam

Arm Type

Experimental

Arm Description

Participants were randomly assigned to receive a dose of 0.045mg/kg of Midazolam (administered Intravenously over 40 minutes with a the maximum total dose allowed in this study of 4.5mg),

Intervention Type

Drug

Intervention Name(s)

Ketamine

Other Intervention Name(s)

Ketalar

Intervention Description

A single dose of 0.5mg/kg of Ketamine will be administered Intravenously during 40 minutes in the Hospital Research Unit of YNHH. The subject will be monitored continuously during the procedure, and every hour for three hours after the infusion.

Intervention Type

Drug

Intervention Name(s)

Midazolam

Other Intervention Name(s)

Versed

Intervention Description

A single dose of 0.045mg/kg of Midazolam will be administered intravenously during 40 minutes in the Hospital Research Unit of YNHH. The subject will be monitored continuously during the procedure, and every hour for three hours after the infusion.

Primary Outcome Measure Information:

Title

Montgomery-Asberg Depression Rating Scale Score 1 Day After Infusion

Description

Time Frame

1 day after the infusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

13 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion: MDD Cohort: Meet DSM-5 criteria for Major Depressive Disorder by structured interview (MINI-KID) CDRS-R score >40. Failure to achieve remission with at least 1 adequate prior antidepressant trial (e.g. SSRI, SNRI, or TCA), meaning at least 8 weeks at therapeutic dosing, including at least 4 weeks of stable dosing. Anxiety Cohort: Meet DSM-5 criteria for any of the following anxiety disorders: Social Anxiety Disorders, Generalized Anxiety Disorder, Separation Anxiety Disorder and/or Panic Disorder by structured interview (MINI-KID) ADIS Clinical Severity Rating ≥4 (moderately severe) for any of the 4 included anxiety disorders Failure to achieve remission with at least 1 adequate prior anxiolytic medication trial (e.g. SSRI, SNRI, or TCA), meaning at least 8 weeks at therapeutic dosing, including at least 4 weeks of stable dosing. Failure to achieve remission with previous CBT or subject declines current CBT therapy Both cohorts: Stable psychiatric medications and doses for the month prior to enrollment. Subjects may continue to engage in any ongoing psychotherapy. Medically and neurologically healthy on the basis of physical examination and medical history. Parents able to provide written informed consent and adolescents must additionally provide assent. Exclusion: Current inpatient hospitalization or active suicidal ideation requiring referral for inpatient hospitalization for safety. History of psychotic disorder or manic episode diagnosed by MINI-KID History of substance dependence diagnosis by MINI-KID (excluding tobacco) or positive urine toxicology. Pregnancy (urine pregnancy tests on the day of scans for menstruating girls). Inability to provide written informed consent according to the Yale Human Investigation Committee (HIC) guidelines in English.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael H. Bloch, MD MS

Organizational Affiliation

Yale University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hospital Research Unit at the Yale New Haven Hospital

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06510

Country

United States

Facility Name

Yale Child Study Center

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06520

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

8122957

Citation

Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB Jr, Charney DS. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry. 1994 Mar;51(3):199-214. doi: 10.1001/archpsyc.1994.03950030035004.

Results Reference

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PubMed Identifier

10686270

Citation

Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. doi: 10.1016/s0006-3223(99)00230-9.

Results Reference

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PubMed Identifier

16894061

Citation

Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856-64. doi: 10.1001/archpsyc.63.8.856.

Results Reference

background

PubMed Identifier

24318540

Citation

Niciu MJ, Ionescu DF, Richards EM, Zarate CA Jr. Glutamate and its receptors in the pathophysiology and treatment of major depressive disorder. J Neural Transm (Vienna). 2014 Aug;121(8):907-24. doi: 10.1007/s00702-013-1130-x. Epub 2013 Dec 8.

Results Reference

background

PubMed Identifier

25169854

Citation

Ballard ED, Ionescu DF, Vande Voort JL, Niciu MJ, Richards EM, Luckenbaugh DA, Brutsche NE, Ameli R, Furey ML, Zarate CA Jr. Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depression and anxiety. J Psychiatr Res. 2014 Nov;58:161-6. doi: 10.1016/j.jpsychires.2014.07.027. Epub 2014 Aug 12.

Results Reference

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Ketamine Infusion for Adolescent Depression and Anxiety

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