Virtually Malpractice

Psychiatric Times, Vol 39, Issue 10,

"As clinicians who took an oath to 'do no harm,' we must educate the public about the dangers and non–standard of care of the growing practice of at-home ketamine."

FROM THE EDITOR

As our society has been slowly returning to our pre-COVID-19 structure, unforeseen dangerous residues from the necessary rapid adoption of telehealth have emerged that demand our attention and reconstruction. One of these is related to the 2021 decision by the Drug Enforcement Administration (DEA) to temporarily allow dispensing of controlled substances (Schedule 2 through Schedule 5) without the prescriber seeing the patient in person, which remains in effect.

A recent article in The Wall Street Journal chronicled the flagrant abuses and dangers in the subsequent prescribing of psychostimulants for presumed attention-deficit/hyperactivity disorder (ADHD) through a virtual platform, during which the psychostimulant prescriber never met with the patient in person for an initial evaluation or subsequent refills.1

This month’s article by Michael D. Banov, MD, and Rachel E. Landrum, MA, provides a disturbing narrative of another unfortunate dangerous residue that is aggressively expanding via venture capitalists and opportunists in the United States due to this loosened DEA restriction: the growing enterprise of at-home virtual ketamine treatment. Both ketamine and esketamine are Schedule 3 drugs, and ketamine has a history of diversion, abuse, and dependence. On the street, ketamine is called Special K.

I was unaware of the rapidly growing at-home ketamine virtual treatment business until I read this article and subsequently researched the current state of this dangerous model of providing access to ketamine without the required medical oversight and monitoring necessary for accurate patient selection and safety. To my astonishment, the Journal of Affective Disorders just published an article online,2 which appears in their October issue, detailing a large prospective open-label study of at-home, sublingual ketamine telehealth for moderate to severe anxiety and depression, stating in the title that it is “safe and effective.” Notably, there is no placebo control group.

In my opinion, the publication of this article in this well-respected journal is irresponsible and dangerous. It gives credibility to a virtual practice that falls far below the standard of care for the treatment of severe depression and also makes claims about safety and efficacy in anxiety. The scales used are the 9-item Patient Health Questionnaire and the 7-item Generalized Anxiety Disorder questionnaire, neither of which would be acceptable end points to assess symptom improvement in clinical trials. Additionally, this study uses “certified behavioral coaches” called guides whose clinical credentials are unclear. However, the Intervention section of the paper states that “guides are not licensed professionals and do not provide psychotherapy.” The sublingual ketamine is mailed to the participants.

In the Methods section, the authors state “the [Mindbloom] platform is accessible through internet search or external physician/provider referral.” However, I could not find a breakdown of the number of individuals who were referred versus the number who were self-selected by looking for a website to receive at-home ketamine. Most concerning is the way “side effects and adverse events were assessed through a single-item self-report measure administered after session 2 and again after session 4 that said, ‘Have you noticed any issues with your physical or mental health since beginning treatment?’ ”

To provide context, ketamine was approved by the US Food and Drug Administration (FDA) in 1970 as a dissociative anesthetic, and its current FDA-approved indications are limited to general anesthesia and moderate to severe chronic pain. An iconic publication by Berman et al3 demonstrated rapid antidepressant activity when intravenous ketamine was infused into patients with severe depression. Over the past 22 years, ketamine has been used off-label for the treatment of severe depression in various clinical settings and formulations (intravenous, intramuscular, intranasal, sublingual, and oral). In 2019, esketamine was approved by the FDA as an intranasal spray to be used in conjunction with a traditional antidepressant for treatment-resistant depression (TRD).

When ketamine is synthesized, it exists as a 50/50 racemic mixture of its 2 mirror-image components: arketamine and esketamine. Both of these racemates have demonstrated antidepressant activity, but, as of today, only esketamine is FDA-approved for TRD. Although head-to-head studies have not been conducted, clinical experience strongly suggests both ketamine and esketamine are effective in some patients with TRD. Of significance, none of these 3 molecules have established clinical efficacy for anxiety disorders, posttraumatic stress disorders, or other psychiatric disorders.

Additionally, due to the clear and well-documented risks of ketamine abuse, misuse, diversion, dependance, teratogenicity, risk of severe hypertension, common adverse effects of dissociation and sedation, and association with interstitial cystitis and cognitive impairment with long-term daily abuse, the FDA approved esketamine for TRD with a mandatory risk evaluation and mitigation strategies (REMS) protocol. There are approximately 60 medications (including clozapine and isotretinoin) for which the FDA requires REMS protocols. The REMS for esketamine requires certification by the clinic/administering prescriber and the dispensing pharmacy, and patient’s informed consent. A REMS treatment form must be filled out and submitted after each dose of esketamine for the duration of treatment.

Patients receiving esketamine are required to have their blood pressure monitored pre-dose, and then 40 minutes and 2 hours after administration. They must remain in the treatment facility for monitoring by a health care professional for a minimum of 2 hours, the time period in which the common adverse effects of dissociation and sedation occur and will likely resolve. Patients agree that they will not drive themselves home or engage in any complex activity until after a good night’s sleep.

The highly structured REMS protocol is required at the administration of each dose to minimize the possible harm to the patient based on more than 50 years of clinical experience with ketamine, which is 50% esketamine.

Keep these facts in mind as you review the Table, which I assembled by searching “at home ketamine” via Google. As clinicians who took an oath to “do no harm,” we must educate the public about the dangers and non–standard of care of the growing practice of at-home ketamine.

Dr Miller is Medical Director, Brain Health, Exeter, New Hampshire; Editor in Chief, Psychiatric TimesTM; Staff Psychiatrist, Seacoast Mental Health Center, Exeter; Consulting Psychiatrist, Exeter Hospital, Exeter; Consulting Psychiatrist, Insight Meditation Society, Barre, Massachusetts.

Dr Miller would like to disclose that he is a member of the Speakers’ Bureau for Janssen.


References

1. Winkler R. Harlan Band’s descent started with an easy online Adderall prescription. The Wall Street Journal. August 19, 2022. Accessed September 12, 2022. https://www.wsj.com/articles/harlan-bands-descent-started-with-an-easy-online-adderall-prescription-11660916158

2. Hull TD, Malgaroli M, Gazzaley A, et al. At-home, sublingual ketamine telehealth is a safe and effective treatment for moderate to severe anxiety and depression: findings from a large, prospective, open-label effectiveness trialJ Affect Disord. 2022;314:59-67.

3. Berman RM, Cappiello A, Anand A, et al. Antidepressant effects of ketamine in depressed patientsBiol Psychiatry. 2000;47(4):351-354.