i-CBT and IV Ketamine for Suicidality in Treatment-Resistant Depression: A Randomized, Midazolam-Controlled Clinical Trial

Summary

Approximately four thousand Canadians die by suicide every year, and suicide is the second leading cause of death in youth and young adults (15-34 years). Most people with depression experience thoughts of suicide and many will also plan and/or attempt suicide at some time in their life. There is an urgent need for new scalable treatments that can effectively reduce suicidality in people with depression.

Cognitive behavioural therapy (CBT) reduces suicidal thoughts and behaviours, and can be delivered through the internet (i-CBT) making it more accessible and scalable. However, i-CBT has not been shown to rapidly reduce suicidal thoughts and behaviours (suicidality), such as within 24 hours. IV ketamine on the other hand has been shown to rapidly reduce thoughts of suicide, but not suicidal behaviours.

Therefore, combining i-CBT with IV ketamine may be more effective reducing suicidality than i-CBT treatment with a control treatment.

The investigators propose a 13-week, multi-site, study that looks at how combining i-CBT and IV ketamine treatment will affect suicidality in individuals with depression who have recently experienced suicidal thoughts and/or behaviours, but have not responded to previous treatment. All 110 participants will receive a weekly session of i-CBT for 13 weeks, but half will be randomly assigned to also receive six IV ketamine treatments or six IV midazolam treatments (control treatment) over the first initial 30 days. The investigators will measure changes in suicidal thoughts and behaviours before drug treatment and at the primary endpoint (i.e.,day 30), and after 3 months (i.e. Day 91) of the starting treatment.

Conditions

• Major Depressive Disorder
• Suicide
• Treatment Resistant Depression

Interventions

DRUG

Ketamine hydrochloride

55 patients will receive ketamine hydrochloride, over six infusions, flexibly dosed between 0.5 mg/kg to 0.85 mg/kg.

BEHAVIORAL

i-CBT (Internet-based Cognitive Behavioural Therapy)

Each week for 13 weeks, participants will watch an online module that last approximately 45-50 mins each, with homework at the end of each module. Homework is submitted and reviewed by a therapist, who will provide personalized feedback before progression to the next module.

DRUG

Midazolam Hydrochloride

55 patients will receive midazolam hydrochloride, over six infusions, flexibly dosed between 0.02 mg/kg to 0.035 mg/kg.

Sponsors & Collaborators

• Ontario Shores Centre for Mental Health Sciences

  collaborator OTHER

• University Health Network, Toronto

  lead OTHER

Principal Investigators

• Rodrigo Mansur · University Health Network, Toronto

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

21 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-01-02

Primary Completion

2026-03-31

Completion

2026-06-30

Countries

• Canada

Study Locations