Treating major depressive disorder remains an important challenge worldwide. The disorder impairs productivity, social functioning, and overall health, reducing life expectancy and burdening health care systems.1 Although many treatments exist, at least a third of patients do not have a response after two or more trials of antidepressant drugs and are considered to have treatment-resistant depression.2 Such patients have an increased risk of suicide relative to both the general population and patients with nonresistant major depressive disorder; at least a third of them attempt suicide.3
The FDA recently approved the S-enantiomer of ketamine, esketamine, a rapidly acting drug shown to be effective in patients with treatment-resistant depression.
Balancing these potential risks with the benefits of an effective drug for a serious disease for which there is substantial unmet need, the FDA approved esketamine with a Risk Evaluation and Mitigation Strategy (REMS). The intent of the REMS is to mitigate the risk of serious adverse outcomes resulting from sedation, dissociation, and abuse and misuse, while providing access to this effective treatment for treatment-resistant depression. Esketamine will be dispensed and administered to patients only in a medically supervised health care setting where they can be monitored for adverse reactions for at least 2 hours; pharmacies that dispense esketamine must ensure that the drug is dispensed only to clinics and hospitals that are certified in the REMS.