Behavioral and Electrophysiological Effects of Ketamine in Treatment-Resistant Depression

The overarching goal of the present study is to evaluate the effect of a subanesthetic dose of ketamine 24-hour post-injection on resting state functional connectivity, cognitive control, and reward learning.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder

Detailed Description

Major Depressive Disorder (MDD) participants with treatment-resistant depression (TRD) will be recruited from McLean's Ketamine clinic. Suitability for Ketamine treatment will be determined as typically done by the service - through evaluation by the clinicians on the staff of the Ketamine Service who perform psychiatric consultations and assessments for Ketamine suitability. Potential subjects will be informed about the study only after they have received a positive consultation at the clinic and have already agreed to receive the treatment.

This study consists of a set of questionnaires, urine drug screen, and electroencephalogram (EEG) recordings.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: David Crowley, ALM; Phone Number: 617-855-4432; Email: djcrowley@mclean.harvard.edu
• Study Contact Backup: Name: Sarah Woronko, BA; Phone Number: 617-855-4431; Email: sworonko@mclean.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • Recruiting
      • McLean Hospital
      • Contact: Jason Scott, BA; Phone Number: 617-855-2247

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

We plan to recruit 30 TRD individuals with current MDD without psychotic features and 30 demographically matched healthy controls. All participants will be ketamine-naïve.

Description

Inclusion Criteria (MDD Subjects):

• All genders, races, and ethnic origins, aged between 18 and 70;
• DSM-5 diagnostic criteria for MDD (diagnosed with the use of the Structured Clinical Interview for DSM-5 (SCID-5));
• A score of ≥32 on the Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30).
• Capable of providing written informed consent, and fluent in English;
• Right-handed;
• Treatment Resistant (as assessed using the MGH Antidepressant Response Questionnaire)
• Have already decided to receive ketamine treatment as part of their standard clinical care

Inclusion Criteria (Control Subjects):

• All genders, races, and ethnic origins, aged between 18 and 70;
• Absence of medical, neurological, and psychiatric illness (including alcohol and substance abuse), as assessed by subject history and a structured clinical interview (SCID-I/NP);
• A baseline Quick Inventory of Depressive Symptomatology (QIDS) score ≤ 5;
• A baseline Hamilton Depression Rating Scale (HDRS) score ≤ 7;
• Capable of providing written informed consent, and fluent in English;
• Right-handed;
• No first-degree relative with mood or psychotic disorder.

Exclusion Criteria (All Subjects):

• Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease;
• History of seizure disorder;
• History or current diagnosis of any of the following DSM-5 psychiatric illnesses: schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, substance abuse disorder;
• Clinical or laboratory evidence of hypothyroidism, hyperthyroidism, or other thyroid disorder that is not controlled by medication;
• Substance use assessed by physician as dangerous for ketamine treatment;
• Untreated glaucoma;
• Complex post-traumatic stress disorder (PTSD) with dissociation;
• Patients with a lifetime history of electroconvulsive therapy (ECT).
• Participants with a lifetime history of ketamine use.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Healthy Controls; Subjects who have no history of clinical depression or other psychological disorder
Current MDD; Subjects experiencing a current episode of Major Depressive Disorder.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feedback-related positivity (FRP) amplitudes over frontocentral scalp regions in response to rewarded trials versus no-reward trials	Relative FRP response is the primary outcome measure for the probabilistic reward task (PRT).	Baseline
Event-related negativity (ERN) amplitudes over frontocentral scalp regions in response to correct trials versus incorrect trials.	Relative ERN response is the primary outcome measure for the flanker task.	Baseline
Behavioral Performance on the Probabilistic Reward Task (PRT)	The Probablilistic Reward Task operationalizes positive reinforcement learning	Baseline
Behavioral Performance on the Flanker Task	The Flanker Task is a cognitive task that measures response inhibition to assess the ability to suppress responses that are inappropriate in a particular context.	Baseline
Rumination	Severity of rumination will be assessed using the Rumination Response Scale (RRS). The RRS has a minimum score of 22 and a maximum score of 88. Higher scores indicate higher degrees of ruminative symptoms.	Baseline

Collaborators and Investigators

• Sponsor: Mclean Hospital
• Investigators: Principal Investigator: Diego Pizzagalli, PhD, McLean Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2020
• Primary Completion (Estimated): March 31, 2024
• Study Completion (Estimated): March 31, 2024

Study Registration Dates

• First Submitted: January 15, 2020
• First Submitted That Met QC Criteria: January 21, 2020
• First Posted (Actual): January 27, 2020

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: 2019P003371

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No