Anxiety DisordersDepressive DisordersSafety & Risk ManagementKetamine

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 trial

This open-label (real-world evidence) paper (n=1247) argues that at-home sublingual ketamine (tablets for under the tongue) is both safe (only four patients dropped out) and effective (remission of 32% for depression and anxiety). Patients only spoke with a 'guide' (not a therapist) over video as the study was conducted during Covid. The results look promising, though the study sponsor (Mindbloom) has come under scrutiny recently.

Authors

  • Adam Gazzaley

Published

Journal of Affective Disorders
individual Study

Abstract

Background

At-home Ketamine-assisted therapy (KAT) with psychosocial support and remote monitoring through telehealth platforms addresses access barriers, including the COVID-19 pandemic. Large-scale evaluation of this approach is needed for questions regarding safety and effectiveness for depression and anxiety.

Methods

In this prospective study, a large outpatient sample received KAT over four weeks through a telehealth provider. Symptoms were assessed using the Patient Health Questionnaire (PHQ-9) for depression, and the Generalized Anxiety Disorder scale (GAD-7) for anxiety. Demographics, adverse events, and patient-reported dissociation were also analyzed. Symptom trajectories were identified using Growth Mixture Modeling, along with outcome predictors.

Results

A sample of 1247 completed treatment with sufficient data, 62.8 % reported a 50 % or greater improvement on the PHQ-9, d = 1.61, and 62.9 % on the GAD-7, d = 1.56. Remission rates were 32.6 % for PHQ-9 and 31.3 % for GAD-7, with 0.9 % deteriorating on the PHQ-9, and 0.6 % on the GAD-7. Four patients left treatment early due to side effects or clinician disqualification, and two more due to adverse events. Three patient subpopulations emerged, characterized by Improvement (79.3 %), Chronic (11.4 %), and Delayed Improvement (9.3 %) for PHQ-9 and GAD-7. Endorsing side effects at Session 2 was associated with delayed symptom improvement, and Chronic patients were more likely than the other two groups to report dissociation at Session 4.

Conclusion

At-home KAT response and remission rates indicated rapid and significant antidepressant and anxiolytic effects. Rates were consistent with laboratory- and clinic-administered ketamine treatment. Patient screening and remote monitoring maintained low levels of adverse events. Future research should assess durability of effects.

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Research Summary of '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 trial'

Introduction

Depressive and anxiety disorders are major and growing contributors to disability, and existing treatment capacity and effectiveness are increasingly seen as inadequate. Earlier research has documented rapid symptom reductions with compounds that have dissociative or psychedelic properties, and ketamine in particular has substantial evidence from intravenous (IV) and intramuscular (IM) studies; sublingual and intranasal forms are emerging because they are easier to deliver. At the same time, telemedicine and remote monitoring have expanded access to mental healthcare, but large-scale evidence is needed on safety and effectiveness when ketamine is delivered at home with psychosocial support via telehealth. Hull and colleagues set out to evaluate the real-world safety and effectiveness of an at-home, sublingual ketamine-assisted therapy (KAT) model delivered through a telemedicine platform. The prospective, open-label study aimed to characterise symptom change in depression and anxiety over four weeks, document adverse events and dissociative reactions, and identify distinct patient response trajectories and their predictors using observational clinical records and routine outcome measures.

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Study Details

  • Study Type
    individual
  • Journal
  • Compound
  • Topics
  • Author
  • APA Citation

    Hull, T. D., Malgaroli, M., Gazzaley, A., Akiki, T. J., Madan, A., Vando, L., Arden, K., Swain, J., Klotz, M., & Paleos, C. (2022). 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 trial. Journal of Affective Disorders, 314, 59-67. https://doi.org/10.1016/j.jad.2022.07.004

Related Clinical Trial

Completed

Real-World Effectiveness of At-Home Sublingual Ketamine Telehealth for Anxiety and Depression: A Retrospective Observational Study

Retrospective real-world analysis (15 US states; January–November 2021; institutional review board approved as exempt) of de-identified routine clinical and quality-management data from a telemedicine ketamine-assisted therapy (KAT) service. Patients completed online eligibility screening followed by a video-based intake with a prescribing psychiatric clinician confirming diagnosis and at-home safety. Inclusion: age ≥18, reliable internet access, clinician-assigned diagnosis of depression (PHQ-9 ≥10) and/or anxiety (GAD-7 ≥10). Exclusion: ketamine allergy, current substance dependence, history of opioid use disorder, active/past psychosis or mania, uncontrolled cardiac disease, pregnancy/nursing, recent suicidal intent or attempt. N=1,247 patients with sufficient outcome data identified from a chart review of approximately 2,848–4,334 records (discrepancy noted in the paper text). Treatment: 300–450 mg rapidly dissolving sublingual ketamine tablets (initial dose ~5 mg/kg, adjusted for dissociative response), mailed to patients; administered at home with a physically present peer monitor and real-time guide support via text during each 8-hour session. Guides provided 30-minute pre- and post-session video calls plus daily text check-ins. Clinicians conducted follow-up video consultations 1–2 days after the first session. Outcomes: PHQ-9 (depression) and GAD-7 (anxiety) assessed at baseline, after Session 2 (week 2), and after Session 4 (week 4). Safety outcomes: C-SSRS suicide screening (baseline), AUDIT, DAST-10, plus real-time vital sign monitoring. Dissociation measured with a 3-item adaptation of the Clinician Administered Dissociative States Scale. Primary analyses included response rate (≥50% score reduction), remission (follow-up score <5 with baseline ≥10), and clinically significant change (≥5-point reduction below clinical threshold). Growth Mixture Modelling (Mplus 8, parallel PHQ-9 and GAD-7 processes) identified latent trajectory classes.

Started
Type
interventional
Randomized
No
Registry ID
DROZDZ-2022-JAD-SUBLINGUAL-KETAMINE-TELEHEALTH

References (8)

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Single versus repeated sessions of ketamine-assisted psychotherapy for people with heroin dependence

Krupitsky, E. M., Burakov, A. M., Dunaevsky, I. V. et al. · Journal of Psychoactive Drugs (2007)

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Luckenbaugh, D. A., Niciu, M. J., Ionescu, D. F. et al. · Journal of Affective Disorders (2014)

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Mcinnes, L. A., Qian, J. J., Gargeya, R. S. et al. · Journal of Affective Disorders (2022)

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Niciu, M. J., Shovestul, B. J., Jaso, B. A. et al. · Journal of Affective Disorders (2018)

A consensus statement on the use of ketamine in the treatment of mood disorders

Sanacora, G., Frye, M. A., McDonald, W. et al. · JAMA Psychiatry (2017)

470 cited
Side-effects associated with ketamine use in depression: a systematic review

Short, B., Fong, J., Galvez, V. et al. · Lancet Psychiatry (2017)

Decreases in Suicidality Following Psychedelic Therapy: A Meta-Analysis of Individual Patient Data Across Clinical Trials

Weissman, C. R., Zeifman, R. J., Yu, D. et al. · Journal of Clinical Psychiatry (2022)

Cited By (5)

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The effects of ketamine on symptoms of depression and anxiety in real-world care settings: a retrospective controlled analysis

Hietamies, T. M., Mcinnes, L. A., Klise, A. J. et al. · Journal of Affective Disorders (2023)

Reconsidering “dissociation” as a predictor of antidepressant efficacy for esketamine

Mathai, D. S., Nayak, S., Yaden, D. B. et al. · Psychopharmacology (2023)

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Oral Ketamine for Depression: An Updated Systematic Review

Meshkat, S., Haikazian, S., Di Vincenzo, J. D. et al. · Biological Psychiatry (2023)

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At-home, sublingual ketamine telehealth is a safe... — Research Summary & Context | Blossom