Comment from Regina Saylor

I am writing in response to the FDA's request for public comment regarding drug repurposing to address unmet medical needs. I am a Board-Certified physician with 8 years of clinical experience. For almost 2 years, I have directly overseen intravenous (IV) ketamine treatment for depression, including patient evaluation, infusion oversight, longitudinal treatment planning, and coordination of care with outside psychiatrists, therapists, and primary care providers. During this time, I have overseen approximately 4,500 ketamine infusions and cared for nearly 500 patients. Based on my clinical experience, I believe IV ketamine represents a compelling candidate for drug repurposing for the treatment of depression. Across the U.S., a substantial number of patients continue to experience severe depressive symptoms despite multiple evidence-based treatments. Many of my patients have failed numerous antidepressant trials, augmentation strategies, and psychotherapy. They often present with significant functional impairment, inability to work or attend school, and suicidal ideation. For most of these patients, IV ketamine has been life-changing. As a provider, I have observed clinically meaningful improvements in depressive symptoms, suicidality, and overall functioning among many patients who had exhausted standard treatment options, and have failed intranasal ketamine as well. One example is a 54 year old Creative Director with lifelong treatment-resistant depression. Prior to treatment, her PHQ-9 score was 24 out of 27, reflecting severe depression. She had previously tried more than a dozen psychiatric medications, electroconvulsive therapy, and was taking 4 psychiatric medications when she initiated IV ketamine treatment. With treatment, her PHQ-9 scores decreased to 4-6, her chronic passive suicidal ideation resolved for the first time in her life, and her functioning improved sufficiently for her to successfully return to work. Another example is a 45 year old school principal who presented in April 2023 with severe depression despite twice-weekly psychotherapy and multiple medication trials. Her PHQ-9 scores ranged from 20 to 23, and she experienced ongoing suicidality. Following consistent IV ketamine treatment, her symptoms steadily improved. Since December 2023, she has remained in sustained remission, with PHQ-9 scores consistently below 5. These examples are representative of outcomes I have observed throughout my practice. Beyond symptom reduction, successful treatment often allows patients to reengage in work, education, relationships, and psychotherapy in ways that were previously impossible because of the severity of their depression. My experience has also demonstrated that IV ketamine can be administered safely within a structured medical setting. Patients undergo comprehensive psychiatric and medical evaluation, receive continuous monitoring during treatment, and are followed longitudinally to optimize outcomes and coordinate care with their existing mental health treatment teams. Yet, despite the clear and safe benefits, many patients are unable to access care as cost represents a significant barrier. Because IV ketamine remains an off-label treatment for depression, most patients must pay entirely out of pocket. I routinely see patients discontinue treatment despite clear clinical benefit because they can no longer afford it. Others receive treatment less frequently than clinically recommended due to financial constraints, increasing the risk of symptom recurrence. Perhaps most concerning are the patients who never initiate treatment at all. Many individuals learn that IV ketamine is generally not covered by insurance and decide not to pursue an evaluation. As clinicians, we only see the patients who make it through the door. There is an unseen population of patients whose access to potentially beneficial treatment is limited not by clinical appropriateness, but by cost. Given the prevalence of treatment-resistant depression, the impact of these barriers is substantial. IV ketamine is unique in that it has accumulated a considerable body of clinical evidence supporting its antidepressant effects, is already being used extensively in clinical practice, and addresses a significant unmet need. In France and Norway, IV ketamine has gained regulatory approval for depression and suicidality due to its superior efficacy compared to intranasal ketamine and due to its lower cost, which substantially increases access. Based on my experience, IV ketamine addresses a significant unmet need for patients with treatment-resistant depression. FDA recognition of IV ketamine for depression could improve access, facilitate insurance coverage, reduce financial barriers, and help ensure that treatment decisions are guided by clinical need rather than a patient's ability to pay. Thank you for considering my perspective and clinical experience.