None listed
Conditions
Brief summary
The proposed intervention involves a single subcutaneous injection of ketamine (0.75 mg/kg) or a matched placebo (0.9% saline) administered to participants with difficult-to-treat depression (DTD). The intervention is delivered under double-blind conditions at the Royal Melbourne Hospital Clinical Trials Centre. The ketamine dose is administered once only and is not part of any ongoing therapeutic protocol. The intervention is designed to investigate neural and clinical changes following ketamine administration, with a particular focus on the habenula (Hb) - a subcortical region implicated in reward processing and mood regulation. The intervention is embedded within a case-control, pre-post imaging study framework. Participants undergo ultra-high field 7-Tesla MRI scans before and 24-48 hours after the injection to assess changes in Hb activity and connectivity. Secondary behavioural and clinical assessments (e.g., MADRS, QIDS-C, SHAPS, GAD-7, actigraphy, and mobile sensing) will evaluate treatment response, mood, circadian regulation, and anhedonia. This intervention is not intended as a clinical treatment but rather as a mechanism-focused investigation. Participants are fully informed that the intervention is experimental and not part of routine care. Safety monitoring includes cardiorespiratory assessment, adverse event screening, and psychiatric review before and after the injection, following established ketamine research protocol.
Interventions
Participants with difficult-to-treat depression will receive a single subcutaneous injection of 0.75mg/kg ketamine. The intervention is administered under medical supervision in a controlled clinical setting. Neuroimaging assessments (7T fMRI) will be conducted pre- and 24-48 hours post-injection to evaluate changes in habenula activity and connectivity.
Sponsors
The University of Melbourne
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Clinical Participants • Age 18 – 65 at the time of informed consent; • Meets DSM-5 criteria for major depressive disorder (MDD), with a current major depressive episode (MDE), confirmed via the MINI • Insufficient response to at least 2 adequate trials of antidepressant medications, as determined by study doctor; • Ability to provide written informed consent (including adequate intellectual capacity and fluency in the English language), as determined by the, study doctor or delegate. Control Participants • Age 18-65; • Ability to provide written informed consent (including both adequate intellectual capacity and fluency in the English language) as determined by a study doctor or delegate; and • No diagnosis of major depressive disorder
Exclusion criteria
Clinical Participants • Severe disturbance such that the patient would be unable to comply with study requirements • History or current diagnosis of a psychotic or bipolar disorder as assessed using the MINI • Any unstable medical condition, or medical or pharmaceutical contraindication to ketamine • Any history of a ketamine use disorder of any severity or moderate-to-severe substance use disorder (for other drugs) within the past 6 months • Contraindications to MRI Control Participants (healthy controls) • Severe disturbances that the participant would be unable to comply with the requirements of informed consent or comply with the study protocol, as determined by a study doctor or delegate; • Any current or past mental health disorder diagnoses as assessed through the MINI; • Any unstable medical condition as determined by the study doctor that may be contraindicative to MRI (e.g., epilepsy); • Currently prescribed psychoactive medication; • Contraindications to MRI
Outcome results
None listed