Ketogenic diet and ketamine infusion treatment to target chronic persistent eating disorder psychopathology in anorexia nervosa: a pilot study

Calabrese, Lori; Scolnick, Barbara; Zupec‐Kania, Beth; Beckwith, Caroline; Costello, Kayla; Frank, Guido

doi:10.1007/s40519-022-01455-x

Cited by 23 publications

(20 citation statements)

References 10 publications

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“…In a small pilot case study, five individuals who regained weight after anorexia nervosa but with chronic constant eating disease psychopathology implemented a therapeutic KD to maintain body weight [ 85 ]. After experiencing nutritional ketosis, individuals were treated with six ketamine infusions and were then followed for around 6 months.…”

Section: Resultsmentioning

confidence: 99%

The Relationship of Ketogenic Diet with Neurodegenerative and Psychiatric Diseases: A Scoping Review from Basic Research to Clinical Practice

et al. 2023

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Background: The ketogenic diet (KD) has become widespread for the therapy of epileptic pathology in childhood and adulthood. In the last few decades, the current re-emergence of its popularity has focused on the treatment of obesity and diabetes mellitus. KD also exerts anti-inflammatory and neuroprotective properties, which could be utilized for the therapy of neurodegenerative and psychiatric disorders. Purpose: This is a thorough, scoping review that aims to summarize and scrutinize the currently available basic research performed in in vitro and in vivo settings, as well as the clinical evidence of the potential beneficial effects of KD against neurodegenerative and psychiatric diseases. This review was conducted to systematically map the research performed in this area as well as identify gaps in knowledge. Methods: We thoroughly explored the most accurate scientific web databases, e.g., PubMed, Scopus, Web of Science, and Google Scholar, to obtain the most recent in vitro and in vivo data from animal studies as well as clinical human surveys from the last twenty years, applying effective and characteristic keywords. Results: Basic research has revealed multiple molecular mechanisms through which KD can exert neuroprotective effects, such as neuroinflammation inhibition, decreased reactive oxygen species (ROS) production, decreased amyloid plaque deposition and microglial activation, protection in dopaminergic neurons, tau hyper-phosphorylation suppression, stimulating mitochondrial biogenesis, enhancing gut microbial diversity, restoration of histone acetylation, and neuron repair promotion. On the other hand, clinical evidence remains scarce. Most existing clinical studies are modest, frequently uncontrolled, and merely assess the short-term impacts of KD. Moreover, several clinical studies had large dropout rates and a considerable lack of compliance assessment, as well as an increased level of heterogeneity in the study design and methodology. Conclusions: KD can exert substantial neuroprotective effects via multiple molecular mechanisms in various neurodegenerative and psychiatric pathological states. Large, long-term, randomized, double-blind, controlled clinical trials with a prospective design are strongly recommended to delineate whether KD may attenuate or even treat neurodegenerative and psychiatric disease development, progression, and symptomatology.

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Section: Resultsmentioning

confidence: 99%

The Relationship of Ketogenic Diet with Neurodegenerative and Psychiatric Diseases: A Scoping Review from Basic Research to Clinical Practice

et al. 2023

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“…These potential mechanisms of action are relevant for both MDD and AN where neuroplasticity and serotonergic signaling may be impaired ( 26 ). Several case studies and case series have provided preliminary evidence for the use of ketamine in patients with MDD and comorbid AN ( 19 , 21 , 24 , 32 ). However, the empirical basis is currently meager and there has been less of a focus on depressive symptoms as a proximal indicator of change in patients, despite other research that investigates novel biologically-based therapeutics in AN (e.g., repetitive transcranial magnetic stimulation to the left dorsolateral prefrontal cortex) suggesting early changes in depression as an indicator of treatment efficacy ( 33 , 34 ).…”

Section: Discussionmentioning

confidence: 99%

“…Most studies combined ketamine administration with psychotherapy and/or dietary intervention [e.g. an eating disorder recovery programme; ( 23 ), or a ketogenic diet; ( 21 , 24 )], and it is unclear how ketamine as a solitary intervention impacts outcomes in patients with eating disorders. Moreover, there are few studies investigating changes in depression and anxiety in patients with AN in particular.…”

Section: Introductionmentioning

confidence: 99%

Case report: Intramuscular ketamine or intranasal esketamine as a treatment in four patients with major depressive disorder and comorbid anorexia nervosa

et al. 2023

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IntroductionA comorbid diagnosis of a depressive disorder is a negative prognostic factor for individuals with AN, and novel treatments are needed to target depressive symptoms in this population. One emerging promising treatment for depressive disorders is ketamine, although there is less research investigating the use of ketamine for alleviating depression in people with AN.Case reportThis study reports on four patients with a lifetime diagnosis of AN and a comorbid diagnosis of major depressive disorder who received either intramuscular ketamine (n = 2) or intranasal esketamine (n = 2) treatment from a private psychiatric clinic. Depressive symptomatology (PHQ-9) was measured prior to (es)ketamine administration on every dosing session and adverse effects were recorded during and after dosing. All patients reported a subjective decrease in depression, although only those administered intranasal esketamine showed a reduction in PHQ-9 depression scores over time. Number of doses ranged from 3 to 23. All patients tolerated treatment well and no serious adverse effects emerged, however nausea/vomiting was experienced by one patient on one dosing session. Weight remained stable in all cases, although notably across all patients, weight at the beginning of treatment was within a “healthy” range.DiscussionThese findings suggest that (es)ketamine may reduce depressive symptoms in people with major depressive disorder and a comorbid diagnosis of AN. Future feasibility and pilot trials are warranted in order to elicit robust data on efficacy, acceptability, safety and tolerability.

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“…The combination of these characteristics leads to severe weight loss (Arcelus et al., 2011; Birmingham et al., 2005) and the highest mortality rate of any psychiatric illness (Arcelus et al., 2011). AN is commonly comorbid with depression (Mandal et al., 2019), including suicidal ideation, and anxiety disorders, including obsessive‐compulsive disorder and post‐traumatic stress disorder (Bühren et al., 2014; Bulik et al., 2008; Hughes, 2012; Kaye et al., 2004; Swinbourne et al., 2012; Woodside & Staab, 2006). There are currently no FDA‐approved pharmacotherapy treatments for AN, and little is known about its etiology (Hermens et al., 2020).…”

Section: Introductionmentioning

confidence: 99%

“…A case study regarding a patient experiencing severe and chronic (15 years) AN resulted in complete and sustained remission after receiving intravenous ketamine infusions in combination with a ketogenic diet (Scolnick et al, 2020). This promising case study has been followed by another, involving five chronic AN subjects (Calabrese, 2022). Another case study highlights an extreme and chronic case of a bulimia nervosa patient reaching complete and enduring remission after ketamine-assisted psychotherapy (Ragnhildstveit et al, 2021).…”

mentioning

confidence: 99%

Individual differences in the positive outcome from adolescent ketamine treatment in a female mouse model of anorexia nervosa involve drebrin A at excitatory synapses of the medial prefrontal cortex

Temizer

Chen

Aoki

2022

Synapse

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Anorexia nervosa (AN) is a mental illness with the highest rates of mortality and relapse, and no approved pharmacological treatment. Using an animal model of AN, called activity-based anorexia (ABA), we showed earlier that a single intraperitoneal injection of ketamine at a dose of 30 mg/kg (30mgKET), but not 3 mg/kg (3mgKET), has a long-lasting effect upon adolescent females of ameliorating anorexia-like symptoms through the following changes: enhanced food consumption and body weight; reduced running and anxiety-like behavior. However, there were also individual differences in the drug's efficacy. We hypothesized that individual differences in ketamine's ameliorative effects involve drebrin A, an F-actin-binding protein known to be required for the activity-dependent trafficking of NMDA receptors (NMDARs). We tested this hypothesis by electron microscopic quantifications of drebrin A immunoreactivity at excitatory synapses of pyramidal neurons (PN) and GABAergic interneurons (GABA-IN) in deep layer 1 of prefrontal cortex (PFC) of these mice. Results reveal that (1) the areal density of excitatory synapses on GABA-IN is greater for the 30mgKET group than the 3mgKET group; (2) the proportion of drebrin A+ excitatory synapses is greater for both PN and GABA-IN of 30mgKET than 3mgKET group. Correlation analyses with behavioral measurements revealed that (3) 30mgKET's protection is associated with reduced levels of drebrin A in the cytoplasm of GABA-IN and higher levels at extrasynaptic membranous sites of PN and GABA-IN; (5) altogether pointing to 30mgKET-induced homeostatic plasticity that engages drebrin A at excitatory synapses of both PN and GABA-IN.

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Ketogenic diet and ketamine infusion treatment to target chronic persistent eating disorder psychopathology in anorexia nervosa: a pilot study

Cited by 23 publications

References 10 publications

The Relationship of Ketogenic Diet with Neurodegenerative and Psychiatric Diseases: A Scoping Review from Basic Research to Clinical Practice

The Relationship of Ketogenic Diet with Neurodegenerative and Psychiatric Diseases: A Scoping Review from Basic Research to Clinical Practice

Case report: Intramuscular ketamine or intranasal esketamine as a treatment in four patients with major depressive disorder and comorbid anorexia nervosa

Individual differences in the positive outcome from adolescent ketamine treatment in a female mouse model of anorexia nervosa involve drebrin A at excitatory synapses of the medial prefrontal cortex

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