At-Home, Sublingual Ketamine Therapy: The Promises and Pitfalls of Psychedelic Telemedicine‍

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Telemedicine platform, Mindbloom, recently published the largest-ever real-world study of Ketamine therapy. In a peer-reviewed article to be published in October 2022 in the Journal of Affective Disorders, the researchers documented the effects of sublingual Ketamine therapy given at home.

Despite being minimally guided and non-invasive, the approach led to faster, more substantial response rates than those seen with traditional antidepressants, talk therapy, and even other forms of Ketamine therapy. The study also raised compelling questions about the role of psychosocial support and dissociation in Ketamine treatment outcomes. 

This guide explores the study’s findings, the research directions it opened, and why some critics still question whether Ketamine and telemedicine belong together. 

At-Home, Sublingual Ketamine Therapy: An Overview

The study focused on a large sample of individuals with moderate to severe depression and anxiety symptoms. They took sublingual, rapidly dissolving tablets over four weeks, receiving preparation and support from a prescribing clinician and a certified guide before and after their sessions. For extra support and safety, participants took the Ketamine with a trusted friend or family member present.

Analyzing the results from 1,247 participants, the researchers found:

• 89% had improvement in their anxiety or depression symptoms.
• 63% had a greater than 50% reduction in their symptoms. 
• 30% of participants entered remission (no remaining symptoms) after four sessions.
• 62% who reported suicidal ideation at baseline no longer did after four sessions.

The low side effect profile further magnified the significance of these results: fewer than 5% of participants reported side effects. 

By comparison, SSRIs must be taken for 10 to 14 weeks to reach the remission rates seen after just four weeks in this study. SSRIs also come with substantial side effects, the most notable among them being emotional blunting (an impaired ability to cry, experience surprise, etc.), a side effect that itself can interfere with healing processes like grieving, identifying and releasing unconscious patterns, and other inner work.

The effects of the at-home Ketamine trial were also more substantial and faster-acting than psychotherapy on its own, which, as the authors note, takes 12 to 16 weeks to achieve a similar remission rate as seen in this study. 

Levels of Psychosocial Support Across Treatment Paradigms

Shortly before their first and after their second session, participants met virtually with guides trained in active listening and reflective techniques. The guides didn’t offer psychotherapy but support as participants prepared for and interrogated the implications of their experiences. 

The approach in this study, termed “Ketamine-assisted therapy” (KAT), was unique for standing in the middle of the spectrum between the two central approaches to Ketamine therapy. It had an interpersonal dimension absent from Ketamine infusion therapy (KIT), a medication-centric approach with little or no psychosocial support. 

Yet because participants only interacted with their guide before and after the treatment or by text message, it was more self-directed than Ketamine-assisted psychotherapy (KAP) where psychotherapy bookends and occurs in conjunction with Ketamine dosing sessions. 

Investigations suggest that participants who receive behavioral support during or after Ketamine sessions have enhanced, longer-lasting effects than those who don’t receive any support. But it’s not yet clear whether the therapeutic modality or licensure of the practitioner providing support influences treatment outcomes. 

This study offered an early yet promising indication that the absence of immediate, in-person guidance didn’t interfere with the treatment’s benefits. But the study occurred over a short timeline of just four weeks. Along with maintenance dosing, psychotherapy is one of the central tools for prolonging Ketamine’s effects. Future research that follows participants over six months or longer will reveal more about how levels of psychosocial support influence treatment outcomes. 

Sublingual vs. IV Ketamine Therapy

Despite its having a significantly lower bioavailability, the sublingual Ketamine approach led to higher response rates than IV Ketamine. The present study found that 63% of patients had a greater than 50% reduction in their symptoms. By contrast, a 2022 analysis of IV Ketamine in a real-world setting reported that only 54% of participants had a greater than 50% reduction in their symptoms.

Researchers have suggested the invasiveness of IV Ketamine therapy may partially explain these differences. Critics of IV Ketamine often voice concerns about the treatment’s capacity to induce “white coat syndrome,” where needles, medical machinery, fluorescent lighting, and other clinical aspects of the setting influence the treatment experience, and in turn, the extent and duration of its antidepressant properties. 

Previous studies have explored the impacts of subjective experiences during Ketamine therapy. For example, researchers published in the European Journal of Neuropsychopharmacology found anxiety responses were significantly higher among people who didn’t respond to treatment, suggesting that Ketamine-induced anxiety may indeed interfere with the level of relief a person finds in the experience. 

The authors of the present study indicated that the noninvasive, sublingual ROA may explain the higher response rates. Future research may look specifically into how the needle-free, at-home aspects of the study influence subjective responses, and in turn, therapy outcomes. 

How Remote Ketamine Therapy Bridges Accessibility and Safety

The growing enthusiasm about telemedicine instead comes in response to the realization we need novel treatments to confront a growing problem. Whether you call it a global mental health crisis or a collective dark night of the soul, the quantities of people seeking support for their mental health are outpacing the number of practitioners available to offer it.

With the underwhelming success rates of tools like antidepressants, there’s an increasing collective interest in holistic approaches that don’t involve reactive symptom control but instead consider a person’s biological, psychological, and social needs simultaneously. Remote Ketamine therapy with psychosocial support brings an emphasis on reflective work together with an accessibility absent from IV and other clinical forms of Ketamine therapy. 

IV Ketamine can cost $500 per infusion, and other ROAs are similarly costly. By contrast, each treatment was between $193 and $250 during the evaluation period in this study. As the authors noted, this was 28% to 83% of the cost of a single IV infusion. 

Remote therapy can also alleviate Ketamine practitioner bandwidth concerns. A single Ketamine-assisted psychotherapy (KAP) session is time-intensive, with sessions being as long as three hours, plus supervised recovery. The time-intensive nature of each session limits the number of individuals a practitioner can see, and it also raises its cost. While the support given by Mindbloom isn’t as intensive as KAP, their approach brings Ketamine therapy to more people and from a perspective more whole-person-minded than other clinically available forms of Ketamine therapy. 

Future Research Directions

Since this study didn’t have a control group, the next step will be a randomized controlled trial directly comparing this approach to standard anxiety and depression treatments.

The following factors are also important lines of investigation for future research.

Dosing

Finding the optimal dosage is a tricky process because Ketamine’s antidepressant effects occur within a small window. Very low doses have minimal effects, but as the dosage increases, its effects reach a “goldilocks” point of maximal effectiveness. Beyond that point, higher doses lead to diminishing returns.

Researchers established dosing by referencing the standard IV dosing of 0.5 mg/kg, then adjusting it to account for the lower bioavailability of the sublingual approach. Participants started at a dose between 300 and 450 mg, which gradually increased to 5 mg/kg over the study’s four-week period. 

It’s worth noting, though, that optimal dosing is subject to debate–other studies have pointed to the viability of lower doses on a longer timeline. Future research may dive deeper into the factors and strategies that influence optimal dosing.

Role of Disassociation

Previous research suggested that acute dissociative experiences with Ketamine result in more robust and longer-lasting antidepressant effects.

Interestingly, this study highlighted the importance of the timing of the dissociation. This study revealed strong and consistent evidence that participants who experienced greater dissociation at the end of treatment had a lower likelihood of both depression and anxiety symptom reduction. 

To unravel more about the complex role of dissociation in Ketamine therapy, future research will examine connections between disassociation timing, the durability of the treatment’s effects, and the baseline severity of the condition under treatment.

Accessibility Across Populations 

A higher proportion of men pursued this treatment approach compared to other forms of digital and in-person mental healthcare. 

The researchers noted that the only large real-world study of KIT didn’t include gender information. This knowledge gap makes it harder to tell whether the higher proportions of men participating in this study were drawn to Ketamine itself, the study’s remote setting, or the ROA.

Upcoming studies will look at how or why this approach removes barriers that ordinarily prevent higher numbers of men from pursuing mental healthcare. 

Why Some Critics Question Ketamine Telehealth on Principle

Given the proper preparation and context, this study offered strong evidence that sublingual Ketamine with psychosocial support can be an effective way to alleviate depression and anxiety symptoms. 

Yet some critics worry that remote treatments emphasize accessibility over personalization. As explained by an article published by Vice, people would ideally choose treatments based on their specific needs, diagnoses, and other individual factors, but cost draws many people to the remote approach. If cost is a person’s primary motivation for receiving the treatment, they might under-emphasize other relevant factors, and increase their likelihood of having a disorienting experience.

Proponents of Ketamine-assisted psychotherapy (KAP) have also pointed out that remote offerings leave out a crucial dimension: the therapeutic container shared by the client and therapist. KAP practitioners strive to create a therapeutic holding environment, a safe and inviting setting deepened by an interpersonal dimension based on the trust and shared intentions between client and therapist. 

KAP practitioners see Ketamine and other psychedelic compounds as catalysts for healing processes directed, first and foremost, by an individual and heightened by their human connection with a trusted practitioner. While people can create and reflect upon their intentions with their guide before or after their sessions, the lack of in-the-moment support from a practitioner might prevent the treatment’s effects from being as far-reaching as they might otherwise be. 

Yet like other questions in psychedelic medicine, we can’t resolve these concerns through speculation alone: the answers lie on the other side of real-world data collection and observation. 

In a world where suicide is the second leading cause of death among people between 25 and 34, the emphasis on safe, accessible psychedelic treatments holds the promise of reaching people who were failed by conventional psychiatry and are unable to access other types of Ketamine therapy. Ongoing research will bring further clarity about the nature of the support most beneficial for people pursuing remote options.

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