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

Depression Clinical Trial

Official title: Safety and Clinical Effects of Intranasal Ketamine in Ultra-REsistant Depression (SURE-ECT Non Responders). Pilot Study

Status Completed

Clinical Trial Summary

Despite the known efficacy of pharmacotherapy (i.e. antidepressants) and psychotherapeutic interventions in treating depressive disorders, research evidence suggests that 20% to 40% of patients with major depressive disorder (MDD) do not respond adequately to such treatments. These patients are diagnosed with Treatment-Resistant Depression (TRD), and are sometimes treated with convulsive therapy. However, about 10-30% of TRD patients do not respond to convulsive therapy, and are thus diagnosed with Ultra-Resistant Depression (URD). Using an open label pilot study involving subjects, this trial aims to assess the safety, tolerability, and clinical effects of intranasal ketamine (IN) treatment in patients who do not respond to convulsive therapy. Intranasal ketamine (IN) treatment approach has shown promising therapeutic outcomes for patients with TRD, but has not yet been studied on patients with URD.

Clinical Trial Description

Ketamine is a fast-acting anesthetic that can have stimulant effects when taken at low doses. It acts as a non-competitive high-affinity N-methyl-d-aspartate (NMDA) receptor antagonist that stimulates synaptic glutamate release and blocks extra-synaptic NMDA receptors. This mechanism of action mediates excitatory synaptic transmission through the central nervous system and therefore results in robust antidepressant effects. Administering intravenous (IV) ketamine to patients with TRD has shown to produce rapid antidepressant effects. Nevertheless, delivering IV ketamine to patients can be challenging since it requires specialized expertise and equipment. A promising alternative that preserves IV ketamine's rapid onset of therapeutic action while minimizing inconvenience and discomfort is intranasal drug delivery (IN). This current proof-of-concept clinical trial is an open label pilot study on patients with treatment-resistant unipolar depression who did not respond to, or did not tolerate, an acute course of convulsive therapy. Using a combination of Transcranial Magnetic Stimulation (TMS) neurophysiological tools with electromyography (EMG) and electroencephalography (EEG), this trial also aims to explore biomarkers of ketamine's antidepressant effect by examining ketamine's action on NMDA neurotransmission. Investigating the impact of ketamine on cortical excitation and inhibition could provide insight into the role of NMDA receptors in cortical physiology, and therefore determine potential predictors of clinical response for depression.

Objective 1: To test the safety and tolerability of IN ketamine in patients with URD who did not respond to/tolerate an acute course of convulsive therapy

Hypothesis 1: IN ketamine will be safe and well tolerated in patients with URD

Objective 2: To test the clinical effects of IN ketamine patients with URD who did not respond to/tolerate an acute course of convulsive therapy

Hypothesis 2: IN ketamine will result in improvement in depressive symptoms, suicidal ideation, and quality of life measures (compared to scores from baseline)

Objective 3: To investigate the impact of ketamine on cortical excitation via intracortical facilitation (ICF) and cortical inhibition via short-interval cortical inhibition (SICI) paradigms

Hypothesis 3: IN ketamine will result in neurophysiological changes as measured by TMS-EMG and EEG ;

Related Conditions & MeSH terms

• Depression
• Depressive Disorder

• NCT number: NCT05137938
• Study type: Interventional
• Source: Centre for Addiction and Mental Health
• Status: Completed
• Phase: N/A
• Start date: October 25, 2021
• Completion date: July 24, 2023