Early Effects of Ketamine vs Placebo With Venlafaxine in Severe Depression Patients

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 synaptogenesis