Safety, effectiveness and tolerability of sublingual ketamine in depression and anxiety: A retrospective study of off-label, at-home use

Ketamine-assisted psychotherapy is a promising new treatment for a variety of mental disorders of adolescence. There is currently an adolescent mental health crisis, with a high prevalence of disorders, diagnostic complexity, and many adolescents failing to respond to conventional treatments. While there is strong evidence for the use of ketamine in adults for a variety of treatment-refractory mental illnesses, research in adolescents is in its early stages. Ketamine-assisted psychotherapy (KAP) has been described in adults with promising results and here we present the first published cases of the use of KAP in adolescents. The four cases include adolescents aged 14–19 at the initiation of treatment, each with a variety of comorbid diagnoses including treatment-resistant depression, bipolar disorder, eating disorders, anxiety, panic, and trauma-related symptoms. They each initially received sublingual ketamine, followed by sessions with intramuscular ketamine. Their courses varied, but each had symptomatic and functional improvements, and the treatment was well-tolerated. Subjective patient reports are included. Rapid resolution of symptomatology and suffering often occurs within months as the result of the application of KAP to adolescent psychiatric care but is not inevitable. Family involvement in the treatment process appears to be essential to success. The development of this modality may have a singularly positive impact that will expand the psychiatric toolbox and its healing potency.

Section: Methodsmentioning

confidence: 99%

Ketamine-assisted psychotherapy in adolescents with multiple psychiatric diagnoses

Wolfson¹,

Andries²,

Ahlers³

et al. 2023

“…In addition to these ECT-like care models, there is also increasing interest in utilizing ketamine in ways more resemblant of oral antidepressants. For example, studies have evaluated at-home sublingual or oral ketamine doses prescribed up to three times per day ( 72 , 73 ). Such approaches are significantly less studied than parenteral ketamine or intranasal esketamine (which also requires in-person administration due to the US Risk Evaluation and Mitigation Strategy) ( 74 ).…”

Section: Methodsmentioning

confidence: 99%

The Montreal model: an integrative biomedical-psychedelic approach to ketamine for severe treatment-resistant depression

Garel,

Drury,

Thibault Lévesque

et al. 2023

BackgroundSubanesthetic ketamine has accumulated meta-analytic evidence for rapid antidepressant effects in treatment-resistant depression (TRD), resulting in both excitement and debate. Many unanswered questions surround ketamine’s mechanisms of action and its integration into real-world psychiatric care, resulting in diverse utilizations that variously resemble electroconvulsive therapy, conventional antidepressants, or serotonergic psychedelics. There is thus an unmet need for clinical approaches to ketamine that are tailored to its unique therapeutic properties.MethodsThis article presents the Montreal model, a comprehensive biopsychosocial approach to ketamine for severe TRD refined over 6 years in public healthcare settings. To contextualize its development, we review the evidence for ketamine as a biomedical and as a psychedelic treatment of depression, emphasizing each perspectives’ strengths, weaknesses, and distinct methods of utilization. We then describe the key clinical experiences and research findings that shaped the model’s various components, which are presented in detail.ResultsThe Montreal model, as implemented in a recent randomized clinical trial, aims to synergistically pair ketamine infusions with conventional and psychedelic biopsychosocial care. Ketamine is broadly conceptualized as a brief intervention that can produce windows of opportunity for enhanced psychiatric care, as well as powerful occasions for psychological growth. The model combines structured psychiatric care and concomitant psychotherapy with six ketamine infusions, administered with psychedelic-inspired nonpharmacological adjuncts including rolling preparative and integrative psychological support.DiscussionOur integrative model aims to bridge the biomedical-psychedelic divide to offer a feasible, flexible, and standardized approach to ketamine for TRD. Our learnings from developing and implementing this psychedelic-inspired model for severe, real-world patients in two academic hospitals may offer valuable insights for the ongoing roll-out of a range of psychedelic therapies. Further research is needed to assess the Montreal model’s effectiveness and hypothesized psychological mechanisms.

“…Though meta-analysis data is positive for PO and SL ketamine ( 97 ), reported doses and frequencies varied widely, ranging from 0.5–1.25 mg/kg (or 50-300 mg for studies which reported total doses only) used multiple times per day to once a month. A recent large ( N = 664) retrospective report of SL ketamine (300-450 mg) used off-label at home demonstrated nearly identical results to IV ketamine when administered as a series of 6 treatments ( 98 ).…”

Section: Clinical Considerationsmentioning

confidence: 99%

“…Some prescribers instead choose not to dose by weight and start ketamine-naïve patients conservatively at 50-100 mg SL or IN, titrating the dose up as tolerated to efficacy. One recent report successfully started ketamine-naïve patients at 300 mg SL and increased as tolerated to 450 mg ( 98 ), but our approach to date has been more conservative. A recent chart review of a sample of patients from our program found SL ketamine was generally started at 50-200 mg, though the most common starting doses were 100 mg and 150 mg.…”

Section: Clinical Considerationsmentioning

confidence: 99%

Use of ketamine for treatment resistant depression: updated review of literature and practical applications to a community ketamine program in Edmonton, Alberta, Canada

Chrenek,

Duong,

Khullar

et al. 2024

BackgroundThough intravenous (IV) ketamine and intranasal (IN) esketamine are noted to be efficacious for treatment-resistant depression (TRD), access to each of these treatments within healthcare systems is limited due to cost, availability, and/or monitoring requirements. IV ketamine has been offered at two public hospital sites in Edmonton, Canada since 2015. Since then, demand for maintenance ketamine treatments has grown. This has required creative solutions for safe, accessible, evidence-based patient care.ObjectivesAims of this paper are twofold. First, we will provide a synthesis of current knowledge with regards to the clinical use of ketamine for TRD. Consideration will be given regarding; off-label racemic ketamine uses versus FDA-approved intranasal esketamine, populations treated, inclusion/exclusion criteria, dosing, assessing clinical response, concomitant medications, and tolerability/safety. Second, this paper will describe our experience as a community case study in applying evidence-based treatment. We will describe application of the literature review to our clinical programming, and in particular focus on cost-effective maintenance treatments, long-term safety concerns, routes of ketamine administration other than via intravenous, and cautious prescribing of ketamine outside of clinically monitored settings.MethodologyWe conducted a literature review of the on the use of ketamine for TRD up to June 30, 2023. Key findings are reviewed, and we describe their application to our ketamine program.ConclusionEvidence for the use of ketamine in resistant depression has grown in recent years, with evolving data to support and direct its clinical use. There is an increasing body of evidence to guide judicious use of ketamine in various clinical circumstances, for a population of patients with a high burden of suffering and morbidity. While large-scale, randomized controlled trials, comparative studies, and longer-term treatment outcomes is lacking, this community case study illustrates that currently available evidence can be applied to real-world clinical settings with complex patients. As cost is often a significant barrier to accessing initial and/or maintenance IV or esketamine treatments, public ketamine programs may incorporate SL or IN ketamine to support a sustainable and accessible treatment model. Three of such models are described.