THE EVIDENCE
STUDIES:
Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical
Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy
Jennifer Dore, Brent Turnipseed, Shannon Dwyer, Andrea Turnipseed
Julane Andries, German Ascani
Pages 189-198 | Received 13 Dec 2018, Accepted 15 Feb 2019, Published online: 27 Mar 2019
Discussion
Previous studies have indicated that IV ketamine infusions can serve as an effective course of treatment for patients with TRD (23, 24). This study aimed to examine the safety and effectiveness of at-home use of SL ketamine for TRD and treatment-resistant anxiety. This study has shown that in as few as three doses of ketamine therapy nearly 50% of patients with moderate to severe depression saw an improvement of reducing their PHQ-9 and GAD-7 scores to half of their intake scores. This reduction rate improved to 60% in patients who completed a clinically recommended six ketamine RDT course of treatment. Of note, for patients with moderate to severe intake GAD-7 scores there was a clinical effect with ketamine therapy of reducing anxiety categorization in as few as three doses, and of those who were with moderate to severe intake GAD-7 scores who completed six ketamine RDT 65.4%, saw their GAD-7 scores reduced to 50% or more of their intake scores. Reductions in scores for those who had only received 3-RDT matched those who had completed 6-RDT (see Figure 2), and it is reasonable to speculate that there would be maintenance of improvement with three additional RDT ketamine treatments.
Our findings indicate that SL ketamine is clinically effective in reducing depression and anxiety in an at-home setting. The use of SL ketamine at home presents a promising approach in the treatment of TRD where treatment resistance may be the result of prior treatment approaches being mismatched with underlying neurobiological etiology. Since most antidepressants target monoaminergic mechanisms, the effectiveness of ketamine’s pharmacological profile suggests an underlying role for glutamate in some individuals who experience TRD (47).
Limitations of the study were that it was a retrospective review of chart data from a self-selecting convenience sample. Measures of depression and anxiety relied extensively on self-report, though there was considerable provider care given. There was no placebo/control group, and given the dissociative effects of ketamine, a strong placebo effect is possible. Caution should be exercised whenever treating patients with depression and anxiety, especially those with complicating presenting symptoms (i.e., suicidality) or health problems (i.e., hypertension, substance abuse). While the majority of patients respond after 3 doses, we did not determine whether there are differences in the durability of response based on the number of treatments,; this an active area of investigation. Further work, which we are currently engaged in, will be needed to delineate not only the most effective dosing regimen, but also to identify likely responders based on patient characteristics and maintain continued analysis of patient data. The researchers also acknowledge the need for continued analysis of patient data. Nonetheless, we argue that SL ketamine offers a safe and effective tool in the treatment of anxiety and depression. This study represents a step toward consideration of at-home, SL ketamine for treatment-resistant depression and treatment-resistant anxiety.
In conclusion, this study adds to a growing literature on the effectiveness of ketamine treatment for TRD (22, 48). The improvements in depression and anxiety symptomology demonstrated in those who received as few as three at-home ketamine RDT present a safe, effective, and reasonable alternative to inpatient IV infusions of ketamine. These improvements in symptoms are further improved with completion of a clinically recommended course of six ketamine RDT. In addition to providing an effective treatment for those with TRD and comorbid anxiety, it also suggests alternative neurobiological modes for understanding MDD and anxiety symptoms. Additional studies including randomized trials, long-term impact on remission rates, combinations with additional psychosocial interventions, other functional outcomes, and cost-effectiveness analysis are needed.
Sublingual Ketamine Demonstrated to Be Safe, Effective for Patients with Treatment-Resistant Depression
Jan 18, 2023
Erin Hunter, Assistant Editor
Research highlights that 6 doses of sublingual ketamine may be more effective than 3 doses, however both can ameliorate symptoms of anxiety and depression.
Prior literature has suggested ketamine may be an alternative pharmacological intervention for patients with depression. It is often delivered via intravenous (IV) infusion, but IV is not cost effective and requires presence in a medical setting. Researchers found a solution in sublingual (SL), rapid dissolving tablets (RDT) that are off-label and for at-home use.
A recent study found that novel SL ketamine is safe and effective for patients with treatment-resistant depression and treatment-resistant anxiety. As little as 3 doses of RDT therapy were found to improve almost half of patients with moderate to severe depression, which they reported on intake scores.
“The use of SL ketamine at home presents a promising approach in the treatment of [treatment-resistant depression],” wrote study authors in a recent article published in the journal Frontiers. “The improvements in depression and anxiety symptomology demonstrated in those who received as few as three at-home ketamine RDT present a safe, effective, and reasonable alternative to inpatient IV infusions of ketamine.”
Treatment-resistant depression is a form of major depressive disorder (MDD) that affects 30% of the 350 million patients with MDD worldwide. Treatment-resistant depression occurs when the patient does not respond to 2 or more first-line treatments of antidepressants—these patients were found to be at higher risk of suicide and other comorbidities.
A previous study determined that 3 doses of SL ketamine at 300/450 mg could produce better intake scores from the accredited Generalized Anxiety Disorder Screener (GAD-7) and Patient Health Questionnaire (PHQ-9) after 4 weeks. This retrospective review follows a similar trajectory, but assesses efficacy and safety of clinical self-administered, off-label ketamine in patients with treatment-resistant depression with symptoms of depression and anxiety on either 3 or 6 doses.
Among patients with moderate to severe depression, 50% improved intake scores with 3 doses—however, 60% of patients who took the clinically recommended 6 ketamine RDT treatment self-reported alleviated symptoms.
“Reductions in scores for those who had only received 3-RDT matched those who had completed 6-RDT, and it is reasonable to speculate that there would be maintenance of improvement with 3 additional RDT ketamine treatments,” study authors wrote in the article.
The findings also suggest that ketamine presents an alternative way to approach neurobiological modes when trying to understand symptoms of depression and anxiety. It is generally safe, with patients most at risk of minor adverse events that include nausea, dizziness, headache, and loss of balance.
The study does include some limitations, such as the retrospective nature of the study. Additionally, measures were self-reported, and researchers included no comparative placebo group. Further, researchers did not investigate the durability based on number of treatments.
“This study represents a step toward consideration of at-home, SL ketamine for treatment-resistant depression and treatment-resistant anxiety,” the authors wrote.
Reference
Hassan K, Struthers W, Sankarabhotia A, et al. Safety, effectiveness and tolerability of sublingual ketamine in depression and anxiety: A retrospective study of off-label, at-home use.Front Psychiatry. 2022;13:992624. doi:10.3389/fpsyt.2022.992624
Abstract
Clinical evidence is accumulating to support the use of ketamine as a powerful, quick-acting intervention for depression. Ketamine has been administered by oral, sublingual, transmucosal, intravenous, intramuscular, subcutaneous, intranasal, and even rectal routes. Whereas intravenous ketamine is the best studied approach, common sense dictates that oral ketamine is the most practical. The bioavailability of oral ketamine and interindividual variations thereof have been poorly studied; possibly only 20%-25% of an oral dose reaches the bloodstream. This is not necessarily a limitation because, as with other drugs that have poor oral bioavailability, compensation is possible by administering an appropriately higher dose, and interindividual variations can be addressed through individualized dose up-titration. A quarter- century of experience supports the use of oral ketamine for treating acute and chronic pain in children and adults. Case reports, case series, chart reviews, and 3 recent randomized controlled trials (RCTs) show that oral ketamine is effective in treating severe depression, depression with suicidal ideation, and treatment-resistant depression; that oral ketamine, used as an augmentation agent, improves outcomes in patients receiving a conventional antidepressant; and that oral ketamine reduces depression in patients with chronic pain. Doses of oral ketamine have ranged from 0.25 to 7 mg/kg and from 50 mg per occasion to 300 mg per occasion in multiple daily dosing, daily dosing, and intermittent dosing schedules. Oral ketamine was well tolerated in all studies; dropout and reasons for dropout were similar in ketamine and control arms in the 3 RCTs. These findings suggest that if ketamine is to find a place as an off-label treatment for depression and suicidality in mainstream psychiatry, researchers should study the safety, efficacy, and optimization of oral ketamine. Intravenous and intranasal routes may be monetarily more promising, but the oral route could be of greatest service.
© Copyright 2019 Physicians Postgraduate Press, Inc.
Berman et al. antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15, 47*4): 351-4. 7 subjects, o.5 mg/kg IV, significant improvements within 72 hours. 14 pt reduction in Hamilton depression rating score vs 0 in placebo
Zarate et al. A randomized trial of NMDA antagonist in Treatment of Depression. Arch Gen psychiatry. 2006. Aug;63(8):856-64. Rapid and robust response. 18 pts
Kryst et al. Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta analysis of randomized clinical trials. Pharmacological reports (2020)
Bahji et al. Ketamine for bipolar depression: a systemic review. International journal of neuropsychopharmacology. 30 april 2021
6 studies, 135 patients
Domany et al. repeated oral ketamine for outpt treatment of resistant depression Br J Psychiatry. 2019 Jan, 214(1):20-26.
41 ppl, 1 mg/kg po 3 xs/week for 21 days
Decreased depressive sx
Arabzadeh et al. Ketamine accelerate response to treatment in major depressive disorder. J Affect Disorder. 2018 81 pts. Zoloft + oral ketamine early improvement 85.4% vs 42.5% with Zoloft alone
Scientific Literature Supporting Ketamine and more
1. Huang YJ et al. New Treatment Strategies of Depression: Based on Mechanisms Related to
Neuroplasticity. Neural Plast. 2017; 2017:4605971.
2. Hamilton et al. Depressive Rumination, the Default-Mode Network, and the Dark Matter of Clinical
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3. Andrade, C. Ketamine for Depression, 1: Clinical Summary of Issues Related to Efficacy, Adverse
Effects, and Mechanism of Action. J Clinical Psychiatry 2017 Apr;78(4):e415-e419.
4. Gaynes BN et al. What Did STAR*D Teach Us? Results From a Large-Scale, Practical, Clinical Trial for
Patients With Depression. Published online 1 Nov 2009. https://doi.org/10.1176/ps.2009.60.11.1439.
5. Zarate CA, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant
major depression.Arch Gen Psychiatry. 2006 Aug;63(8):856-64.
6. Aan Het Rot M et al. Ketamine for depression: where do we go from here? Biol. Psychiatry. 2012 Oct
1;72(7):537-47.
7. DiazGranados N et al. Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-
aspartate antagonist in patients with treatment-resistant major depressive disorder. J. Clin. Psychiatry.
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8. https://www.nimh.nih.gov/about/directors/thomas-insel/blog/2014/ketamine.shtml
9. Jennifer Dore et al. Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and
Outcomes in Three Large Practices Administering Ketamine with Psychotherapy, Journal of Psychoactive
Additional studies:
Front Psychiatry. 2021; 12: 803279.
Published online 2022 Jan 12. doi: 10.3389/fpsyt.2021.803279
PMCID: PMC8790057
PMID: 35095617
A Cohort-Based Case Report: The Impact of Ketamine-Assisted Therapy Embedded in a Community of Practice Framework for Healthcare Providers With PTSD and Depression
Shannon Dames, 1 , * Pamela Kryskow, 1 and Crosbie Watler 2
Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence
Chittaranjan Andrade 1
Affiliations expand
• PMID: 30946543
• DOI: 10.4088/JCP.19f12820