Harding also pointed to the gap between trial populations and patients seen in practice; the latter often have more advanced illness and more medical and psychiatric comorbidities. She also named logistics as an issue. Treatment centers must be certified under a Risk Evaluation and Mitigation Strategy (REMS), and staff must be able to manage both physiologic events and dysphoric reactions. She said these demands help explain why the drug is underused.<\/p>\n
The Ketamine Regulatory Gap<\/p>\n
Miller asked why racemic ketamine can be given orally, sublingually, intramuscularly, or intravenously, and even mailed to patients, without the REMS rules that govern esketamine. Harding noted that regulators do not govern off-label prescribing. In her view, the larger problem is that ketamine is a Schedule III substance. Pandemic-era relaxation of the Ryan Haight Act’s in-person evaluation rule allowed prescribing across state lines, and some may have exploited this fault.<\/p>\n
Racemic ketamine was approved as an anesthetic meant to stay in the hospital, so it never needed a REMS. Harding said gaps in compounding pharmacy rules, reporting to prescription drug monitoring programs, and data sharing between states have created “a legal loophole that has been exploited.” She cited news reports in which families linked suicides to oral ketamine mailed to their homes. She also noted that the FDA, through the Reagan-Udall Foundation, held a 2-day public meeting on ketamine use in 2024.<\/p>\n
Patient Selection Drives Outcomes<\/p>\n
Harding estimates she has given esketamine more than 10,000 times. She credits her outcomes to careful screening, not to the drug itself. Patients must first be medically cleared, since contraindications include aneurysmal vascular disease. They must then fit the psychiatric criteria. According to her business manager, about 30 of every 1000 screened patients go on to treatment.<\/p>\n
“The crux of this is screening the appropriate patient for the treatment,” Harding said. “The right patient has to be treated, and to reduce the amount of treatment emergent adverse events, it is patient preparation.”<\/p>\n
Dr Miller\u00a0is Medical Director, Brain Health, Exeter, New Hampshire; Editor in Chief, Psychiatric Times; Volunteer Consulting Psychiatrist, Seacoast Mental Health Center, Exeter; Consulting Psychiatrist, Insight Meditation Society, Barre, Massachusetts.<\/p>\n
Dr Harding\u00a0is an assistant clinical professor at Yale School of Medicine, and is the medical director at the Mood Institute.<\/p>\n
References<\/p>\n
1. Berman RM, Cappiello A, Anand A, et al. Antidepressant effects of ketamine in depressed patients.<\/a> Biol Psychiatry. 2000;47(4):351-354.<\/p>\n