Clinical TrialTreatment-Resistant Depression (TRD)KetamineCompleted

Intranasal Ketamine in Ultra-REsistant Depression (SURE-ECT Non Responders) (SURE-ECT)

This open-label pilot trial (n=25) will assess the safety, tolerability, and clinical effects of intranasal ketamine (IN) treatment in patients with Ultra-Resistant Depression (URD) who have not responded to convulsive therapy.

Target Enrollment
25 participants
Study Type
Phase NA interventional
Design
Non-randomized

Detailed Description

Open-label, single-group proof-of-concept study testing intranasal ketamine in outpatients with ultra‑resistant major depressive disorder who did not respond to or could not tolerate an acute course of convulsive therapy.

Intervention consists of intranasal ketamine administered via MAD300 atomiser twice weekly for four weeks (up to 8 sessions) with weight-based titration; patients monitored for 2 hours post-dose with vitals every 30 minutes; labetalol available for transient hypertension.

Outcomes include safety/tolerability, depressive symptom change (HRSD-24), suicidal ideation and quality of life measures, and neurophysiological biomarkers using TMS-EMG and EEG to assess cortical excitation and inhibition.

Study Protocol

Preparation

sessions

Dosing

8 sessions
120 min each

Integration

sessions

Study Arms & Interventions

Intranasal Ketamine

experimental

Open-label intranasal ketamine administered twice weekly for four weeks with weight-based titration using MAD300 atomiser; 2‑hour monitoring per session.

Interventions

  • Ketamine
    via Other• twice weekly for 4 weeks• 8 doses total

    Intranasal administration via MAD300 atomiser; weight-based starting dose with titration; monitoring for 2 hours post-dose with vitals every 30 min; labetalol available for transient hypertension.

Participants

Ages
21 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Individuals with a diagnosis of non-psychotic MDD as confirmed by the Mini-International Neuropsychiatric Interview (MINI)
  • 2. Individuals meeting criteria for Ultra Resistant Major Depressive Disorder (URD) in current episode
  • URD is defined as:
  • a. those who received at least eight convulsive therapy treatment sessions and did not respond, or
  • b. those who were not able to tolerate convulsive therapy
  • 3. Individuals scoring 14 and above on the Hamilton Rating Scale for Depression-24 Items (HRSD-24)
  • 4. Individuals capable to provide consent who are receiving care as outpatients

Exclusion Criteria

  • Exclusion Criteria:
  • 1. History of substance use disorder (dependence or abuse) within the past month; lifetime history of ketamine substance use disorder as confirmed by the MINI
  • 2. Concomitant major unstable medical illness such as poorly controlled high blood pressure or urinary issues (e.g., enlarged prostate)
  • 3. Pregnancy, intention to become pregnant, or breastfeeding; females of reproductive potential must use effective contraception or abstinence
  • 4. Presence of cardiac decompensation/heart failure
  • 5. Diagnosis of any primary psychotic disorder, bipolar disorder, obsessive-compulsive disorder, or current PTSD as confirmed by the MINI
  • 6. Diagnosis of severe personality disorder as assessed prior to study entry
  • 7. Significant neurological disorder (e.g., space occupying lesion, stroke, aneurysm, seizure disorder, Parkinson's, Huntington's, MS)
  • 8. Medical condition, medication, or laboratory abnormality that could cause major depressive episode or significant cognitive impairment per investigator
  • 9. Requirement for benzodiazepine equivalent to lorazepam ≥2 mg/day; use of anticonvulsants (e.g., lamotrigine) and/or opioid medications
  • 10. Inability to communicate in spoken/written English sufficiently to complete assessments
  • 11. Cognitive or physical impairment that may interfere with intranasal administration or 2‑hr monitoring
  • 12. Any intracranial implant or metal object near the head that cannot be safely removed (TMS-EMG/EEG contraindication)
  • 13. Unable to secure an escort to accompany them home after sessions
  • 14. Known allergy to ketamine or any component of the preparation

Study Details

Locations

Centre for Addiction and Mental Health — Toronto, Ontario, Canada

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