Ketamine Infusion for Adolescent Depression and Anxiety

NCT02579928 | Completed Phase 4 Results

• 1 other identifier: 1506016041
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

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).

Conditions

Major Depressive Disorder; Anxiety Disorder

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Ketamine

EXPERIMENTAL

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).

Drug: Ketamine

Midazolam

EXPERIMENTAL

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),

Drug: Midazolam

Interventions

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.

Also known as: Ketalar

Ketamine

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.

Also known as: Versed

Midazolam

Eligibility Criteria

• Age: 13 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead
• American Academy of Child Adolescent Psychiatry.: collaborator

Study Sites (2)

Hospital Research Unit at the Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Yale Child Study Center

New Haven, Connecticut, 06520, United States

Location

Related Publications (7)

• 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.

  PMID: 8122957 BACKGROUND

• 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.

  PMID: 10686270 BACKGROUND

• 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.

  PMID: 16894061 BACKGROUND

• 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.

  PMID: 24318540 BACKGROUND

• 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.

  PMID: 25169854 BACKGROUND

• Lineham A, Avila-Quintero VJ, Bloch MH, Dwyer J. Exploring Predictors of Ketamine Response in Adolescent Treatment-Resistant Depression. J Child Adolesc Psychopharmacol. 2024 Mar;34(2):73-79. doi: 10.1089/cap.2023.0047. Epub 2024 Jan 3.

  PMID: 38170185 DERIVED

• Lineham A, Avila-Quintero VJ, Bloch MH, Dwyer J. The Relationship Between Acute Dissociative Effects Induced by Ketamine and Treatment Response in Adolescent Patients with Treatment-Resistant Depression. J Child Adolesc Psychopharmacol. 2023 Feb;33(1):20-26. doi: 10.1089/cap.2022.0086.

  PMID: 36799961 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Anxiety Disorders; Depression; Phobia, School; Suicide; Generalized Anxiety Disorder; Suicidal Ideation

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Phobic Disorders; Self-Injurious Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

The small sample size and the smaller number of subjects who were randomized to receive ketamine prior to midazolam.

Results Point of Contact

• Title: Dr. Michael H. Bloch
• Organization: Yale University

michael.bloch@yale.edu

2037374539

Study Officials

• Michael H. Bloch, MD MS

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 16, 2015
• First Posted: October 20, 2015
• Study Start: October 1, 2015
• Primary Completion: September 28, 2018
• Study Completion: September 1, 2019
• Last Updated: July 14, 2020
• Results First Posted: March 16, 2020

Record last verified: 2020-06

Locations

US (2)