This randomised, quadruple-blind, placebo-controlled Phase III trial (n=60) will study the early effects of ketamine compared to placebo as an adjunctive therapy with venlafaxine in inpatients with severe unipolar major depressive disorder (MDD).
Participants will receive three doses of intravenous ketamine (35mg/70kg) or a placebo, alongside standard venlafaxine treatment over a week.
The study, sponsored by Assistance Publique – Hôpitaux de Paris, aims to evaluate the rapid efficacy of ketamine in reducing depressive symptoms, as measured by the Hamilton Depression Rating Scale (HDRS). It will also assess biomarkers, synaptic density variations via PET-MRI, and the correlation between ketamine’s efficacy and synaptogenesis.
The trial will take place across three locations in France and is expected to begin in September 2024, with completion anticipated by April 2026.
Trial Details
Unipolar major depressive disorder is the leading cause of disability worldwide. The most commonly used treatments for major depressive episodes (MDE) are antidepressant medications. However, they have limited efficacy and their onset of action is long, ranging between 2 to 6 weeks. During this period, hospitalization can become necessary, especially for severe MDE. It is crucial to improve the early effectiveness of treatments for these patients in order to alleviate their suffering, limit complications (suicidal risk), and reduce hospitalization durations (approximately 1000 euros per day). The efficacy of intravenous ketamine has been demonstrated in pharmaco-resistant depression but remains to be proven in non-pharmaco-resistant severe MDE. Additionally, PET imaging using [11C]UCB-J, which allows the in vivo study of synaptic density in the human brain, has shown significant decreases in synaptic density in unipolar patients with severe MDE. Furthermore, a single ketamine infusion was found to enhance synaptogenesisNCT Number NCT06508710
?>