Real world effectiveness of repeated ketamine infusions for treatment-resistant depression with comorbid borderline personality disorder

Danayan, Kevork; Chisamore, Noah; Rodrigues, Nelson B.; Vincenzo, Joshua D. Di; Meshkat, Shakila; Doyle, Zoe; Mansur, Rodrigo B.; Phan, Lee; Fancy, Farhan; Chau, Edmond; Tabassum, Aniqa; Kratiuk, Kevin; Arekapudi, Anil; Teopiz, Kayla M.; McIntyre, Roger S.; Rosenblat, Joshua D.

doi:10.1016/j.psychres.2023.115133

Cited by 11 publications

(7 citation statements)

References 28 publications

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“…The argument for the potential of psychedelic therapy in BPD ( Zeifman and Wagner, 2020 ) may arise, in part, from reported benefits in disorders often comorbid with BPD—for example, MDD, post-traumatic stress disorder, substance abuse ( Bogenschutz et al, 2015 ; Bouso et al, 2008 ; Carhart-Harris et al, 2021b ) including improvements in some key symptoms of BPD (e.g., suicidality, emotion dysregulation, self-image) ( Argento et al, 2017 ; Domínguez-Clavé et al, 2019 ; Soler et al, 2018 ; Zeifman et al, 2022 ). More recently, a small number of pilot studies and case reports have tested this directly, administering ketamine or ayahuasca to patients with BPD, reporting no adverse effects and reductions in suicidal ideation and behavioral symptom severity ( Danayan et al, 2023 ; Fineberg et al, 2023 ; Nandan et al, 2022 ; Purohith et al, 2021 ; Zeifman et al, 2019 ). Future case studies may help address whether any histories of suspected BPD and related psychological complexity can account for notable complex or adverse responses to classic psychedelic therapy.…”

Section: Discussionmentioning

confidence: 99%

Psychiatric risks for worsened mental health after psychedelic use

Marrocu,

Kettner,

Weiss

et al. 2024

J Psychopharmacol

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Background: Resurgent psychedelic research has largely supported the safety and efficacy of psychedelic therapy for the treatment of various psychiatric disorders. As psychedelic use and therapy increase in prevalence, so does the importance of understanding associated risks. Cases of prolonged negative psychological responses to psychedelic therapy seem to be rare; however, studies are limited by biases and small sample sizes. The current analytical approach was motivated by the question of whether rare but significant adverse effects have been under-sampled in psychedelic research studies. Methods: A “bottom margin analysis” approach was taken to focus on negative responders to psychedelic use in a pool of naturalistic, observational prospective studies ( N = 807). We define “negative response” by a clinically meaningful decline in a generic index of mental health, that is, one standard error from the mean decrease in psychological well-being 4 weeks post-psychedelic use (vs pre-use baseline). We then assessed whether a history of diagnosed mental illness can predict negative responses. Results: We find that 16% of the cohort falls into the “negative responder” subset. Parsing the sample by self-reported history of psychiatric diagnoses, results revealed a disproportionate prevalence of negative responses among those reporting a prior personality disorder diagnosis (31%). One multivariate regression model indicated a greater than four-fold elevated risk of adverse psychological responses to psychedelics in the personality disorder subsample ( b = 1.425, p < 0.05). Conclusion: We infer that the presence of a personality disorder may represent an elevated risk for psychedelic use and hypothesize that the importance of psychological support and good therapeutic alliance may be increased in this population.

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Section: Discussionmentioning

confidence: 99%

Psychiatric risks for worsened mental health after psychedelic use

Marrocu,

Kettner,

Weiss

et al. 2024

J Psychopharmacol

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“…Dissociative symptoms were mild and transient in both groups. Relevant limitations of the study included retrospective and open-label design and short (1 week) follow-up after final infusion ( 117 ).…”

Section: Ketamine/esketamine Trials and Case Studies In Bpdmentioning

confidence: 99%

Depression with comorbid borderline personality disorder - could ketamine be a treatment catalyst?

Więdłocha,

Marcinowicz,

Komarnicki

et al. 2024

Front. Psychiatry

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Borderline personality disorder (BPD) is diagnosed in 10-30% of patients with major depressive disorder (MDD), and the frequency of MDD among individuals with BPD reaches over 80%. The comorbidity of MDD and BPD is associated with more severe depressive symptoms and functional impairment, higher risk of treatment resistance and increased suicidality. The effectiveness of ketamine usage in treatment resistant depression (TRD) has been demonstrated in numerous studies. In most of these studies, individuals with BPD were not excluded, thus given the high co-occurrence of these disorders, it is possible that the beneficial effects of ketamine also extend to the subpopulation with comorbid TRD and BPD. However, no protocols were developed that would account for comorbidity. Moreover, psychotherapeutic interventions, which may be crucial for achieving a lasting therapeutic effect in TRD and BPD comorbidity, were not included. In the article, we discuss the results of a small number of existing studies and case reports on the use of ketamine in depressive disorders with comorbid BPD. We elucidate how, at the molecular and brain network levels, ketamine can impact the neurobiology and symptoms of BPD. Furthermore, we explore whether ketamine-induced neuroplasticity, augmented by psychotherapy, could be of use in alleviating core BPD-related symptoms such as emotional dysregulation, self-identity disturbances and self-harming behaviors. We also discuss the potential of ketamine-assisted psychotherapy (KAP) in BPD treatment. As there is no standard approach to the application of ketamine or KAP in individuals with comorbid TRD and BPD, we consider further research in the field as imperative. The priorities should include development of dedicated protocols, distinguishing subpopulations that may benefit most from such treatment and investigating factors that may influence its effectiveness and safety.

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“…The presence of psychiatric comorbidities (including borderline personality disorder) does not significantly affect treatment outcomes or efficacy in a meaningful way ( 30 , 31 ). Exclusion criteria include a primary psychotic disorder, uncontrolled hypertension, central aneurysmal disease, significant valvular disease, recent cardiovascular event (within 6 weeks), and class 3 heart failure (New York Heart Association) as per CANMAT recommendations ( 32 ).…”

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

Front. Psychiatry

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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.

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Real world effectiveness of repeated ketamine infusions for treatment-resistant depression with comorbid borderline personality disorder

Cited by 11 publications

References 28 publications

Psychiatric risks for worsened mental health after psychedelic use

Psychiatric risks for worsened mental health after psychedelic use

Depression with comorbid borderline personality disorder - could ketamine be a treatment catalyst?

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

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