At-home ketamine treatment initiated by an online provider presents many legal, clinical, and ethical challenges…
PSYCHIATRY & SOCIETY
Case Vignette 1
“Mr Brad,” a 46-year-old, employed man, is seen in our clinic for medication management of chronic unipolar depression, generalized anxiety, and attention-deficit/hyperactivity disorder. At his most recent visit, he proactively shared that he was in the process of starting at-home ketamine through an online health care provider. He has tried various antidepressant and antianxiety medications, including 9 infusions of intravenous ketamine over the years for his mental health symptoms, with mixed results. His current medications include aripiprazole 10 mg, desvenlafaxine 100 mg, clonazepam 0.5 mg QID, and mixed amphetamine salts 20 mg QID. Although his symptoms have improved and he is functioning well, he still reports some mild, low-grade depression and anxiety.
Mr Brad underwent a virtual assessment with a multistate licensed online health care provider (HCP) who was physically located in another geographic area. According to the patient, he shared his medical history, medications, and current symptoms. He was not asked to sign a release, and we were not contacted by the HCP. This presented a clinical dilemma as to our role, responsibility, and liability if we continued to treat the patient with these medicines while he was receiving at-home ketamine though another provider.
There has been a recent proliferation of online health care businesses that offer at-home ketamine through virtual visits to patients suffering from a variety of mental health conditions. Ketamine is FDA approved for anesthesia and pain management but not for depression or any other psychiatric disorder.1 HCPs in many countries, however, can prescribe ketamine off label for nonapproved indications.2
Ketamine can be rapid acting and studies have shown effectiveness in treatment-resistant depression (TRD), suicidal ideation, and other psychiatric conditions.3,4 The therapeutic effects are often attributed to its antagonistic effects on the NMDA receptor, 1 of 4 subtypes of inotropic glutamate receptors located throughout the central nervous system.5
Ketamine is a dissociative drug with abuse potential. The dissociative and altered state seen with ketamine may play an important role in its therapeutic benefits. Increased attention in the lay literature and on social media on ketamine as a psychiatric treatment alternative, as well as a tool to facilitate psychotherapy through its mind-expanding properties, has led more patients to seek out this potential therapy, with or without their HCP’s consent.
Simultaneously, there has been an uptick in utilization of online telehealth providers, particularly in mental health. This has been accelerated with technology advances, increased investor interest in this business model, and COVID-19 limiting in-office health care. These businesses claim to make mental health care more convenient, affordable, and accessible by offering care in locations with few mental health care providers.
Access to ketamine as a treatment option can be challenging to interested patients. Many HCPs are reluctant to suggest or use ketamine since it is not approved for psychiatric conditions. Psychiatrists more accepting of ketamine as a treatment option may not have the staff, space, training, or equipment to administer the medication in their offices. Nonpsychiatric health care practitioners including anesthesiologists, mid-level anesthetists, and other HCPs may be skilled at ketamine administration but not in managing patients with treatment-resistant psychiatric disorders. Ketamine therapy can be costly since it is often not covered by insurance.
Esketamine has some similar pharmacokinetic and pharmacodynamic properties to ketamine since it is an isomer of the medication and is FDA approved for TRD and major depression with suicidal ideation. Access to esketamine is limited since many insurances are reluctant to approve this treatment. Few mental health practitioners offer this treatment since they do not have the office space, comfort level, or ability to navigate the complex insurance obstacles restricting payment.6
Recently, several telehealth companies have emerged offering virtual assessments and at-home ketamine delivery, including but not limited to Mindbloom, My Ketamine Home, and Smith Family MD.7-9 These companies specifically market to those looking for ketamine treatment. While promoting at-home ketamine for treatment of psychiatric disorders, many of these companies are led by medical directors without mental health training. Mindbloom, one of the largest such virtual, at-home services, does have psychiatric physicians on its leadership team, including 2 chairmen and vice chairmen of psychiatric hospital departments and a former chief medical officer of the US Department of Health and Human Services.7
In 2008, the Ryan Haight Online Pharmacy Consumer Protection Act was passed after a 17-year-old boy died of an opiate overdose prescribed through a telemedicine consult.10 This law limited the prescribing of controlled substances through telemedicine consult without a face-to-face encounter and an adequate medical evaluation. In 2021, with COVID-19 affecting in-person health care, the Drug Enforcement Administration temporarily loosened the prescribing restrictions of Scheduled II-V controlled substances (CS).11,12 There is a legislative push to continue these lessened restrictions post-COVID.13
Case Vignette 2
“Mr Ryan” is a 65-year-old man who agreed to be interviewed regarding his experience with at-home oral ketamine prescribed through an online provider. Mr Ryan has suffered from dysthymia and mild anxiety without much relief from medication or counseling. He has used psychedelics including LSD, psilocybin, and mescaline for spiritual growth and as a mind-expanding practice. He denies any history of recreational drug use. He reached out to 1 of the telehealth companies offering at-home ketamine after reading an article about the potential benefits of this therapy.
He paid an upfront fee for a package, which included an initial online meeting, follow-up, and exit assessment with a nurse practitioner (NP), 2 sessions with a ketamine “guide,” 6 doses of oral ketamine, and a kit that included a blood pressure cuff, eye mask, educational resources, journal, pen, and audio program to listen to during dosing.
The initial assessment was conducted virtually over 30 minutes in which he was asked about his symptoms, drug experiences, height, weight, medical history, and expectation of treatment. He had to show his blood pressure reading from his cuff. He was not asked to share his health care providers’ names, to sign releases for his HCPs, or to provide any blood work.
He was then sent 450 mg of oral dissolvable ketamine to his home. On the day of dosing, he had a virtual session with his guide during which he was told what to expect during dosing and how to take the medication, given therapeutic readings, and instructed to set an intention for the experience. He had to show his blood pressure readings and have someone else in the home with him before dosing. The guide was not online during the entire session but was available if needed. Mr Ryan was instructed to check in 1 hour after dosing.
Mr Ryan experienced a moderately high level of dissociation with no significant adverse effects. He found it to be pleasant and therapeutic. He had a follow-up visit with the prescribing nurse practitioner a few days later and was then sent all 5 remaining treatments at 750 mg per dose. He met virtually with the guide for the second session. During the last 4 sessions, he was not required to show any more blood pressure readings or to meet with the guide or the NP. He had unlimited access to the guide via texting if he desired.
After his sixth treatment, Mr Ryan had a virtual exit visit with the NP and was offered another 6 doses without a guide for a lower fee. He could pay extra for the guide as well as for an audio program for depression, anxiety, or self-esteem. Although his experience was positive overall, he did have some concerns about the level of monitoring. He would prefer an in-person, more closely supervised experience if it was affordable and available in a warm, therapeutic setting rather than a sterile, medical office environment.
The Risks of At-Home Ketamine
At-home ketamine treatment initiated by an online provider presents many legal, clinical, and ethical challenges to HCPs and potential risks to patients. Some legal questions are whether online prescribing of ketamine, a Schedule III medication, meets criteria for the looser rules of prescribing a CS without an in-person examination, particularly if ketamine is being used for a mind-expanding, emotionally cathartic purpose. The current law states that the prescription must be for a legitimate medical purpose by a practitioner in their usual course of their professional role.12 Whether this meets that definition could be an area of debate. Additionally, by continuing their psychiatric medications and other treatment while they are receiving at-home ketamine, is a clinician giving consent to this treatment? Is a clinician liable if there are complications or drug interactions with a medication they are prescribing during at-home ketamine administration?
Issues of safety evoke clinical questions as to who should be prescribing concomitant psychiatric medicines during ketamine use. There may be medical and/or psychiatric changes related to ketamine dosing that could require alterations in the medication regimen. Although most side effects of ketamine are mild and transient, there are potentially serious safety concerns including elevations in blood pressure, anxiety, severe dissociation, delirium, mania, and psychosis.14 Long-term risks of therapeutic ketamine dosing remain unknown.
Although there are no specific guidelines for off-label ketamine administration, there are standards of care that often include a dosing range based on weight, a medical screening that typically includes baseline blood work, and, in many cases, drug screens and an EKG, along with coordination of care with the patient’s HCPs. Most clinicians dosing ketamine will follow blood pressure, pulse, and, in some cases, pulse oximetry and cardiac monitoring by a trained health care professional during each treatment. Esketamine shares many of the same risks as racemic ketamine and was approved with the restriction that it could only be administered under a Risk Evaluation and Mitigation Strategy (REMS) program.15 REMS is for certain medications with serious safety concerns to help ensure the benefits outweigh the risks. There is required registration and training for the patients, HCPs, and pharmacists. There is a 2-hour minimum observation by a medical professional and blood pressure monitoring in office with a prescriber onsite.
With the self-administration and availability of multiple dosing with at-home ketamine, there is an opportunity for intentional or unintentional overadherence and overdosing. There is a risk with combining at-home ketamine with alcohol or drugs of abuse including opiates, amphetamines, or benzodiazepines, or with legitimately prescribed medications that could have serious and life-threatening interactions.
Table. Bioavailability Comparison: Routes of Ketamine Administration
This also raises questions as to whether oral ketamine is even efficacious in the treatment of any psychiatric condition. Ketamine been most studied with intravenous administration starting at doses of 0.5 mg/kg. There are only 2 randomized control studies looking at antidepressant efficacy of oral ketamine in which much lower doses were used than those given by many online prescribers.16 Most other studies are small case reports and series.17 Oral ketamine has low and varied bioavailability (Table), leading to questions such as what is the safe and effective dose to prescribe?18 Additionally, ketamine is a drug of abuse with street value. Online practitioners sending multiple doses at once puts the patients at risk of overdose, abuse, and diversion.19
We made the decision to notify Mr Brad that we did not agree with his decision to undergo at-home ketamine. Our concern was whether this was an appropriate treatment for him and what we perceived was inadequate at-home monitoring. Furthermore, we were not comfortable with the concomitant use of benzodiazepines and high-dose stimulants. We suggested that if he was going to continue this treatment against our recommendation, he taper off both of those medications. We informed him that we felt it was unsafe for us to continue managing his psychiatric medications while he was self-administering ketamine at home.
This case illustrates an important issue that clinicians will likely soon confront (if they are not encountering it already). Although at-home ketamine is a reality for now, it is conceivable that similar issues may arise with other off-label or unproven therapies, including the much-hyped psychedelic medicines, becoming available to our patients. Access to these therapies, even when illegal, is becoming easier, and government agencies, medical regulatory bodies, and clinicians need to be prepared to manage these situations as they arise.
Dr Banov is a psychiatrist at PsychAtlanta/PsychAtlanta Research Center and on the faculty in the Department of Psychiatry at the Medical College of Georgia. Dr Banov reports disclosures as a speaker for AbbVie, Supernus, Janssen, Intracellular Therapies, and Teva. Ms Landrum is an MD candidate at the Louisiana State University Health Sciences Center.
Acknowledgment: Thanks to Marla Fleming, APRN, for her assistance in this article.
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