The Use of Ketamine for Trauma, Pain and Depression in Health Care – Legal Intelligencer Article

March 2024 Legal Intelligencer/Law.com article by Lamb McErlane attorneys Vasilios J. Kalogredis, Esq. and Sonal Parekh, Esq.
In recent years there has been a dramatic increase in (i) the focus on wellbeing and therapy and (ii) recognition that many forms of trauma and depression can be resistant to conventional treatment and medications. In response, psychedelic-related therapies, such as the use of ketamine, have become more popular. Ketamine, which was once used primarily as a recreational drug, is now being administered in clinics throughout the United States to treat patients suffering from trauma, pain, and depression.
Background
Ketamine is a Schedule III Controlled Substance[1] (i.e., a substance with a moderate to low potential for physical and psychological dependence).[2] While ketamine was approved in 1970 as an injectable anesthetic for certain diagnostic and surgical procedures, in 2019 the Food and Drug Administration (“FDA”) approved the nasal spray, Spravato (esketamine, an enantiomer of ketamine), for treatment-resistant depression and depressive symptoms associated with acute suicidal ideation or behavior in adults. Because the use of ketamine is emerging in a complex legal and regulatory environment, health care providers should be aware of, and ensure compliance with, the legal and regulatory landscape surrounding the use of ketamine. This article provides a summary of the basic legal requirements, cautionary considerations, and additional recommendations with regard to the use and intranasal administration of ketamine that health care providers and/or ketamine clinics should follow.
Minimum Requirements
Spravato has been approved for treatment-resistant depression. Patients with major depressive disorder, who despite trying at least two antidepressant treatments given at adequate doses for an adequate duration in the current episode, have not responded to treatment are considered to have treatment-resistant depression. Spravato is to be used in conjunction with an oral antidepressant. Spravato labeling contains a Boxed Warning that cautions that patients are at risk for sedation and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors after administration (“Safety Concerns”). Because of these Safety Concerns, Spravato is only available through a restricted distribution system under a Risk Evaluation and Mitigation Strategy (“REMS”) and must be administered in a certified medical office where the health care provider can monitor the patient for at least 2 hours after administration. Spravato must be dispensed with a patient Medication Guide that outlines the drug’s uses and risks. Additionally, the prescriber and patient are both required to sign a Patient Enrollment Form that clearly states that the patient understands they should make arrangements to safely leave the health care setting to get home and should not operate heavy machinery on the day of administration.
Because Spravato is self-administered under the supervision of a health care provider in a certified doctor’s office or clinic, and cannot be taken home, the provider should instruct the patient on how to administer Spravato and should check the patient before and after administration to make a determination on when the patient is ready to leave.
Adhering to these requirements should be a top priority of all providers administering Spravato and similar ketamine medications. For example, in January there was a case where 2 doctors were indicted on 22 felony counts for, in part, illegally administering ketamine in a manner that constituted health care fraud.[3] Specifically, a doctor illegally administered intravenous ketamine and a nasal spray version of ketamine: (1) without being personally authorized; (2) in a clinic, the location of which was not authorized; and (3) outside of the direct supervision mandated under REMS. As shown in the case, the illegal distribution of a controlled substance carries a penalty of up to 10 years in prison, a fine of $500,000, or both.
Cautionary Considerations
- Compounded Ketamine
Some practitioners have turned to compounded ketamine to treat depression. Since compounded drugs have not been approved by the FDA, there is a lack of standardized safety measures for the use of compounded ketamine, which may expose patients to an adverse event or lead to potential patient misuse and abuse of compounded ketamine. The FDA’s Adverse Event Reporting System (FAERS) has shown compounded ketamine to vary from Spravato in concentration, dosing, and frequency leading to adverse events, abuse and misuse. In most of these cases, the compounded ketamine was self-administered at home outside the supervision of a health care professional. In addition to the lack of standardized safety measures for compounded ketamine nasal sprays, the FDA cautions health care providers to not treat compounded ketamine in the same way as Spravato because compounded ketamine includes both the R- and S-enantiomers of ketamine, whereas Spravato is comprised of only the S-enantiomer. Health care providers should be advised that animal studies have shown an association between the R-enantiomer (or racemic ketamine) and brain lesions, with the implications to human left unknown. Accordingly, the FDA advises that compounded drugs should only be used in patients whose medical needs cannot be met by an FDA-approved drug.
- Licensure and Corporate Practice of Medicine
Whether a ketamine clinic, or medical clinic that administers ketamine, (hereinafter collectively referred to as “ketamine clinic”) will need a specific regulatory facility license will depend on the state in which it is located. Health care providers should note that both the health care provider and the office location of the ketamine clinic should be registered with REMS and the DEA. Depending upon the model of the clinic, a pharmacy permit may also be necessary.
The ownership structure of the clinic may affect licensing and practice requirements. Ketamine clinics prescribing and administering ketamine could be considered as participating in the corporate practice of medicine, depending on ownership structure and the clinic’s location. The corporate practice of medicine (“CPOM”) is a legal doctrine that prohibits non-physician owned corporations and other non-professional entities from practicing medicine or employing healthcare practitioners to furnish professional medical services.[4]
Accordingly, ketamine clinics should be advised to ensure the clinic (and its health care providers) are professionally licensed under state law, registered with the DEA, certified through REMS, and compliant with the CPOM doctrine applicable to the state in which the clinic is located.
Additional Recommendations
Because the use of ketamine is a developing field, there is no long-standing adoption of a standard of care. Ketamine clinics and health care providers should ensure to follow Federal and State guidelines regarding the use and administration of Ketamine. For clinics and health care providers in Pennsylvania, Prescribing Guidelines for Safe Administration of Low-Dose Ketamine can be found on the Pennsylvania Department of Health website.
Ketamine clinics should be sure to implement standard operating procedures for the delivery of ketamine treatment and should cover topics including informed consent, monitoring patient vitals, post-treatment evaluation, and patient transportation after administration. Maintaining documentation regarding the administration of ketamine, as well as comprehensive training for health care providers, is always a recommended practice.
Last, health care providers and ketamine clinics should evaluate their professional liability insurance coverage to ensure the use of ketamine for treatment of depression is covered. A ketamine intravenous infusion for the treatment of depression is not approved by the FDA and is considered to be an off-label treatment. Health care providers should be aware that ketamine is generally not covered by professional liability insurance for its off-label treatment of depression or other psychiatric disorders. Promoting off-label treatment of FDA-approved medication may be common and medically beneficial to patients, but the promotion of such use places health care providers at a heightened professional risk.
Conclusion
As the use of ketamine for the treatment of depression becomes more popular, health care providers, ketamine clinics, and other health care entities that administer ketamine should ensure that they are continuously meeting the minimum standards required to prescribe, dispense and administer ketamine. Before implementing the use of ketamine within their practice, they should ensure that (i) all necessary licensure, registration, and/or certification for both the entity and providers are in place; (ii) the health care entity’s ownership structure is in compliance with applicable law; (iii) standard operating procedures are implemented (and adhered to); (iv) the professional liability insurance in place covers the use of ketamine for depression; and (v) patients receiving ketamine are eligible for ketamine treatment and provide informed consent.
If you are concerned about compliance and regulations surrounding the use and administration of ketamine in your practice, feel free to contact Vasilios J. Kalogredis, Esq. at bkalogredis@lambmcerlane.com or 610-701-4402 or Sonal Parekh, Esq. at sparekh@lambmcerlane.com or 610-701-4416.
Click here to read the article in the Legal Intelligencer/Law.com.
[1] 21 C.F.R. § 1308.13.
[2] U.S. Dep’t of Justice, Drug Enforcement Admin., Drug Scheduling, https://www.dea.gov/drug-information/drug-scheduling (last visited Mar. 15, 2024).
[3] See St. Louis Area Doctors Accused of Illegally Administering Ketamine, Health Care Fraud, United States Attorney’s Office Eastern District of Missouri, January 11, 2024, https://www.justice.gov/usao-edmo/pr/st-louis-area-doctors-accused-illegally-administering-ketamine.
[4] The Corporate Practice of Medicine is state specific as it relates to prohibitions and professions that fall under its purview. This must be critically analyzed by an attorney who knows and understands the “rules” for the jurisdiction in question.
__________________________________________________________
Vasilios J. (Bill) Kalogredis, Esq. has been advising physicians, dentists, and other healthcare professionals and their businesses as to contractual, regulatory and transactional matters for over 45 years. He is Chairman of Lamb McErlane PC’s Health Law Department. Bill can be reached by email at bkalogredis@lambmcerlane.com or by phone at 610-701-4402.
Sonal Parekh, Esq., who contributed to this article, is a practicing attorney at Lamb McErlane PC who focuses on healthcare transactional matters and a broad range of healthcare regulatory-related issues on behalf of healthcare systems, physicians, dentists, and other healthcare providers, and is a pharmacist by education and training. Sonal can be reached by email at sparekh@lambmcerlane.com or by phone at 610-701-4416.
*This article is for educational purposes only and is not intended to be legal advice. Should you require legal advice on this topic or have any questions or concerns, please contact Vasilios J. (Bill) Kalogredis, Esq. or Sonal Parekh, Esq.
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