Promoting the Discussion of the Beneficial Effects of Ketamine to Treat Refractory Depression

We read a recent article published by CNN titled “Ketamine offers lifeline for people with severe depression, suicidal thoughts1” with great interest. The article traces the story of a man with a 35-year history of severe refractory depression, suicidal ideation, and recent suicide attempts who was successfully treated with ketamine as a last resort after failing dozens of other pharmacologic psychiatric medications, including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and tricyclic antidepressants. This incredible medical success story is not isolated to this gentleman. In fact, there has been significant data, with seven placebo controlled randomized clinical trials (RCT), that have shown the beneficial effects of ketamine infusion therapy on refractory depression.2 However, ketamine therapy for refractory depression in practice is still very limited since it continues to be an off-label use of ketamine. Unfortunately, there are currently no large scale, randomized controlled clinical trials that demonstrate the safety or durability of ketamine therapy. Another limiting factor is that patient selection criteria is limited to major depressive disorder (MDD) without psychotic features with effects lasting up to 1 week, as this is the only population and timeline successfully studied. However, there is evidence that other patients and repeated dosing could be significantly beneficial but there are no clinical trials to fully support this theory. Due to the limitations of trials demonstrating the above factors, the on-label approval of ketamine for psychiatric illness has not undergone scrutiny by the FDA.