The Effect of Ketamine on Aesthetics and Role for Antidepressant Effects

Unraveling the Aesthetic Mind in Anhedonia, Insights From Pharmacological Imaging of the Human Brain: A Single-blind, Randomized, Placebo-controlled Cross-over Study

The aim of this study is to assess the impact of ketamine on aesthetic perception and processing. This study assesses the role of these effects in facilitating ketamine's antidepressant properties, with a focus on anhedonia. To address this aim, 25 patients with major depressive disorder and 35 healthy controls will be assessed twice with magnetic resonance imaging, once after administration of intravenous ketamine (subanesthetic dose) and once after administration of placebo.This study has a single-center, placebo-controlled, cross-over study design. During MRI, structural, resting state, and functional imaging will be performed. Functional imaging will comprise aesthetic processing, reward, and sexual arousal paradigms. In addition, various neuropsychological scales assessing depressive symptoms, anhedonia, and aesthetic processing will be performed. Eligibility for participation will be assessed during a screening visit, a follow up visit will end study participation.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Ketamine

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Rupert Lanzenberger, MD; Phone Number: 35760 0043 1 40400; Email: rupert.lanzenberger@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Contact: Rupert Lanzenberger, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• General health based on medical history and physical examination
• Psychiatric health based on structured clinical interview for DSM-5 (SCID) for healthy controls
• Major depressive episode (first or recurrent) based on structured clinical interview for DSM-5 and ICD-10 for patients
• Age 18 to 55 years
• Right-handedness (due to potential lateralization effects of lefthanded subjects)
• Willingness and competence to sign the informed consent form

Exclusion Criteria:

• Current or history of neurological disease
• Current medical illness requiring treatment
• Psychiatric diagnosis for healthy individuals
• Psychiatric comorbidity with the exception of anxiety disorders for depressed individuals
• Pregnancy or current breastfeeding
• Current or former substance abuse
• Previous ketamine use in lifetime
• Any contraindication for MRI (e.g., MR incompatible implants, etc.) including dental implants causing signal artifacts
• Failure to comply with the study protocol or to follow the instruction of the investigating team

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine first, then placebo; 0.5mg/kg bodyweight (or 0.25mg/kg bodyweight) ketamine, will be determined in pilot study, then placebo	Drug: Placebo; 0.9% NaCl; Drug: Ketamine; 0.5mg/kg bodyweight (or 0.25mg/kg bodyweight) ketamine, will be determined in pilot study
Experimental: Placebo frist, then ketamine; 0.9% NaCl, then ketamine	Drug: Placebo; 0.9% NaCl; Drug: Ketamine; 0.5mg/kg bodyweight (or 0.25mg/kg bodyweight) ketamine, will be determined in pilot study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BOLD signal assessed with fMRI during aesthetic paradigm	Difference in Blood Oxygen Level Dependent (BOLD) signal assessed with functional magnetic resonance imaging (fMRI) between ketamine and placebo condition during an aesthetic processing task	Change from baseline to up to 4 weeks
BOLD signal assessed with fMRI during reward paradigm	Difference in Blood Oxygen Level Dependent (BOLD) signal assessed with functional magnetic resonance imaging (fMRI) between ketamine and placebo condition during a reward processing task	Change from baseline to up to 4 weeks
BOLD signal assessed with fMRI during sexual arousal paradigm	Difference in Blood Oxygen Level Dependent (BOLD) signal assessed with functional magnetic resonance imaging (fMRI) between ketamine and placebo condition during a sexual arousal paradigm	Change from baseline to up to 4 weeks
Levels of pleasantness assessed during aesthetic fMRI task	Level of pleasantness (Numbered scale) of aesthetic stimuli during aesthetic paradigm task	Change from baseline to up to 4 weeks
Number of of chills assessed during aesthetic fMRI task	Number of chills in response to aesthetic stimuli during aesthetic paradigm task	Change from baseline to up to 4 weeks
BOLD signal assessed with fMRI during resting state	Difference in Blood Oxygen Level Dependent (BOLD) signal assessed with functional magnetic resonance imaging (fMRI) between ketamine and placebo condition during resting state	Change from baseline to up to 4 weeks

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): February 28, 2025

Study Registration Dates

• First Submitted: February 26, 2022
• First Submitted That Met QC Criteria: April 8, 2022
• First Posted (Actual): April 11, 2022

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: PSY-NIL-0010

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No