Ketamine Infusion for Adolescent Depression and Anxiety

Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02579928
• Other study ID #: 1506016041
• Status: Completed
• Phase: Phase 4
• Start date: October 2015
• Est. completion date: September 2019

Study information

• Verified date: June 2020
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: September 2019
• Est. primary completion date: September 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anxiety Disorder
• Anxiety Disorders
• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Disease
• Major Depressive Disorder

Intervention

Drug:
• Ketamine
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
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.

Locations

Country	Name	City	State
United States	Hospital Research Unit at the Yale New Haven Hospital	New Haven	Connecticut
United States	Yale Child Study Center	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	American Academy of Child Adolescent Psychiatry.

Country where clinical trial is conducted

United States, 

References & Publications (5)

Ballard ED, Ionescu DF, Vande Voort JL, Niciu MJ, Richards EM, Luckenbaugh DA, Brutsché 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. — View 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. — View 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. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	1 day after the infusion