Ketamine Infusion for Adolescent Depression and Anxiety

Ketamine

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).

Intervention / Treatment

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.

Ketamine (DRUG)

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.
Midazolam (DRUG)

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.

Condition or Disease

Major Depressive Disorder
Anxiety Disorder

Phase

Phase 4

Study Design

Study type:	INTERVENTIONAL
Status:	Completed
Study results:	No Results Available
Age:	13 Years to 17 Years
Enrollment:	17 (ACTUAL)
Funded by:	Other
Allocation:	Randomized
Primary Purpose:	Treatment
Masking 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 QUADRUPLE: Participant Care Provider Investigator Outcomes Assessor

Clinical Trial Dates

Start date:	Oct 01, 2015
Primary Completion:	Sep 28, 2018	ACTUAL
Completion Date:	Sep 01, 2019	ACTUAL
Study First Posted:	Oct 20, 2015	ESTIMATED
Results First Posted:	Mar 16, 2020	ACTUAL
Last Updated:	Jun 29, 2020

Sponsors / Collaborators

Lead Sponsor: Yale University

Lead sponsor is responsible party

Responsible Party: N/A

Location

New Haven, Connecticut, USA

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.

Participant Groups

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),

Eligibility Criteria

Sex:	All
Minimum Age:	13
Maximum Age:	17
Age Groups:	Child
Healthy Volunteers:	Yes

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.

Primary Outcomes

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.

More Details

NCT Number:	NCT02579928
Other IDs:	1506016041
Study URL:	https://clinicaltrials.gov/study/NCT02579928

Last updated: Sep 29, 2023