Abstract
This cross-sectional study evaluates the prevalence of false or misleading information in online direct-to-consumer advertising for off-label and unapproved ketamine in Maryland.
Introduction
Online direct-to-consumer (DTC) advertisements for prescription drugs, depending on context, are variously regulated by the US Food and Drug Administration, the Federal Trade Commission, and/or state consumer protection statutes. Specific requirements vary in rigor, and existing guidelines focus on manufacturers, distributers, and packers of prescription drugs—designations that do not appear to include clinics and telemedicine platforms that provide access to prescription drugs.1,2 One market of concern in this gray area of advertising relates to subanesthetic ketamine.1,2,3 Advertisers may promote intravenous infusions and/or oral formulations, depicted as an emerging treatment for mental health conditions.1,2 Intravenous ketamine is not FDA approved to treat any mental health condition and is used off-label for this purpose. Oral formulations are compounded, unapproved drugs often advertised to induce a hallucinogenic experience at home. In this study, we evaluated online DTC advertising of off-label and unapproved ketamine in Maryland.
Methods
For this cross-sectional study, we identified online DTC ketamine advertisers with at least 1 clinic in Maryland and a website. We identified advertisers from 6 national ketamine clinic databases (eTable 1 in Supplement 1). We supplemented this list with advertisers identified through a geolocated Google search centered in Baltimore, Maryland. Advertiser websites were documented by creating archived site-level directories of all component webpages, excluding blogs. Two researchers (M.A.C. and M.J.D.) extracted information in March 2023 on types, costs, and uses of advertised ketamine services as well as claims regarding safety and regulatory status promulgated by ketamine advertisers. Website analysis methods are detailed in the eMethods in Supplement 1. Claims were determined to be false or misleading if they contradicted evidence accumulated through a multidisciplinary review or contradicted FDA statements (eTable 2 in Supplement 1).4 We followed the STROBE reporting guidelines. This work was performed to brief Maryland regulators. This study used data from publicly available websites. In accordance with 45 CFR §46, we did not submit the study to an institutional review board for approval because it did not involve human participants.
Results
We identified 17 advertisers operating in Maryland across 26 individual locations as of March 2023. Advertisers most frequently promoted infusions (n = 13) or ketamine-assisted therapy (n = 9), with several advertisers also providing on-label use of esketamine (n = 6). Ketamine was offered for a wide range of potential indications, including depression (n = 17), posttraumatic stress disorder (n = 17), anxiety (n = 14), and chronic pain (n = 13). Less common indications advertised included Lyme disease, substance use disorder, alcohol use disorder, and opioid withdrawal. Published cost per infusion varied widely (range, $360-$2500), as did services publicized by specific advertisers. Consultations were often free but could cost up to $390 (Table 1).
Table 1. Services Offered by 17 Maryland Ketamine Advertisers and Associated Cost.
Services listed | No. of clinics advertising servicea | Cost disclosed, $b | Cost range, $b |
---|---|---|---|
Infusionc | 13 | 7 | 360-2500 |
Ketamine-assisted psychotherapyd | 9 | 2 | 150-500 |
Consultatione | 9 | 9 | 0-390 |
Esketaminef | 6 | 2 | 250-300 |
Intramuscular injection | 2 | 1 | 450 |
Oralg | 2 | 1 | 89 |
Intranasalh | 1 | 1 | 300 |
Not all advertisers provided a specific inventory of services offered.
Not all advertisers provided cost for the services offered. The range provided represents data from clinics that did provide these data.
Cost per infusion varied by different dimensions. Some advertisers offered a first-visit discount. Others charged different costs by different indications (eg, a mood disorder would be priced differently compared with a chronic pain disorder).
Ketamine-assisted psychotherapy (also known as KAP or ketamine assisted-therapy [KAT]) refers to the use of ketamine as an adjunct to psychotherapy sessions.
Consultations were free at times and at other times a fee was charged to determine whether ketamine therapy would be appropriate.
Esketamine, a nasal-spray S-enantiomer of ketamine, is approved by the US Food and Drug Administration for treatment-resistant depression and acute suicidality under highly restricted treatment protocols. Esketamine and ketamine are distinct drugs with different regulatory requirements.
Two advertisers offered oral lozenges by which to consume unapproved ketamine. The $89 price point was provided as a weekly fee.
One advertiser specifically offered unapproved intranasal ketamine, distinct from esketamine, which is also provided via the intranasal route. The $300 price was listed per prescription, and the intranasal ketamine was offered in conjunction with an intravenous ketamine infusion.
Table 2 summarizes risk disclosures and claims about ketamine’s regulatory status. Seven of the 17 advertisers failed to disclose any potential adverse effects, including risk of abuse associated with use of ketamine. Three advertisers falsely stated that ketamine was nonaddictive. One advertiser falsely stated that ketamine was FDA approved to treat depression. Ten advertisers did not disclose that their advertised services represent off-label use of ketamine, and all 3 advertisers offering unapproved ketamine formulations failed to disclose this unapproved status.
Table 2. Claims on Maryland Ketamine Advertiser Webpages.
No. (%) of advertisers (N = 17) | |
---|---|
Risk disclosure | |
Did not disclose risk of adverse effects or risk of addiction or misusea,b | 7 (41.1) |
Falsely described ketamine as nonaddictivec | 3 (17.6) |
Did not disclose risk of driving or operating machinery after treatmenta | 9 (52.9) |
Regulatory language | |
Falsely stated FDA approval of an off-label indication | 1 (5.9) |
Failed to disclose off-label nature of treatmenta | 10 (58.8) |
Failed to disclose unapproved nature of oral/intranasal treatmenta | 3/3 (100) |
Abbreviation: FDA, US Food and Drug Administration.
Claims and risk disclosures were examined throughout all webpages on each advertiser’s website. Claims and the presence or absence of risk disclosures were counted in this analysis if they were true throughout all webpages analyzed.
Adverse effects were broadly defined as anything the patient may experience after treatment that would not be considered therapeutic.
Ketamine is classified as a Schedule III controlled substance by the US Drug Enforcement Administration, conveying a moderate-to-low potential for abuse. There is a significant and documented risk of addiction and misuse at subanesthetic doses.4
Discussion
Our analysis of Maryland ketamine DTC advertising showed numerous misleading representations regarding treatment safety and efficacy. Ketamine is not the only example of this type of advertising; a secret shopper study on DTC platforms providing testosterone therapy uncovered prevalent guideline-discordant care.5 Despite potential benefits of ketamine in treating select mental health conditions, well-founded concerns have been raised regarding similarities with opioid prescribing and the risk of widespread misuse.6
This work has limitations. Our sample included only Maryland advertisers, which may not represent the entire country. Furthermore, information on websites may not reflect all information provided to patients. Despite these limitations, our findings point to a concerning regulatory environment that may not adequately protect consumers and holds substantial potential for patient harm.
eMethods. Methodology for Website Analysis
eTable 1. Ketamine Directories Examined
eTable 2. Evidence of False or Misleading Status of Claims
eReferences
Data Sharing Statement
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eMethods. Methodology for Website Analysis
eTable 1. Ketamine Directories Examined
eTable 2. Evidence of False or Misleading Status of Claims
eReferences
Data Sharing Statement