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

      case-report

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          Abstract

          Purpose

          Anorexia nervosa (AN) is a severe psychiatric disorder, and shape and weight concerns are often chronic despite weight normalization. No specific treatments exist for those preoccupations that interfere with recovery and trigger relapse. A case study using a ketogenic diet followed by ketamine infusions led to sustained remission in one patient with chronic AN. Here we conducted an open-label trial to test whether this response could be replicated.

          Methods

          Five adults weight recovered from AN but with persistent eating disorder thoughts and behaviors adopted a therapeutic ketogenic diet (TKD) aimed at maintaining weight. After sustaining nutritional ketosis, participants received six ketamine infusions and were followed over 6 months.

          Results

          All participants completed the study protocol without significant adverse effects. Two participants maintained TKD for 8 weeks prior to ketamine infusions due to good behavioral response and remained on TKD. Three participants received TKD for 4 weeks prior to and during ketamine, then tapered off after the final infusion. The group showed significant improvements on the Clinical Impairment Assessment ( p = 0.008), Eating Disorder Examination Questionnaire (EDEQ) Global score ( p = 0.006), EDEQ-Eating Concerns ( p = 0.005), EDEQ-Shape Concerns ( p = 0.016), EDEQ-Weight Concerns ( p = 0.032), Eating Disorders Recovery Questionnaire (EDRQ) Acceptance of Self and Body (0.027) and EDRQ-Social and Emotional Connection ( p = 0.001). Weight remained stable, except for one participant who relapsed 4 months after treatment and off TKD.

          Conclusion

          This novel treatment appears to be safe and effective for adults with chronic AN-related psychopathology. The results from this open trial support that there are specific neurobiological underpinnings of AN that can be normalized using TKD and ketamine.

          Level of evidence

          Level IV, multiple time series with intervention

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s40519-022-01455-x.

          Related collections

          Most cited references11

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          Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

          Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
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            The effects of ketamine on dopaminergic function: meta-analysis and review of the implications for neuropsychiatric disorders

            Ketamine is a non-competitive antagonist at the N-methyl-d-aspartate receptor. It has recently been found to have antidepressant effects and is a drug of abuse, suggesting it may have dopaminergic effects. To examine the effect of ketamine on the dopamine systems, we carried out a systematic review and meta-analysis of dopamine measures in the rodent, human and primate brain following acute and chronic ketamine administration relative to a drug-free baseline or control condition. Systematic search of PubMed and PsychInfo electronic databases yielded 40 original peer-reviewed studies. There were sufficient rodent studies of the acute effects of ketamine at sub-anaesthetic doses for meta-analysis. Acute ketamine administration in rodents is associated with significantly increased dopamine levels in the cortex (Hedge’s g= 1.33, P 100 mg kg−1) of ketamine on dopamine levels ex vivo, although this remains to be tested in vivo. Findings in non-human primates and in human studies using positron emission tomography were not consistent. The studies reviewed here provide evidence that acute ketamine administration leads to dopamine release in the rodent brain. We discuss the inter-species variation in the ketamine induced dopamine release as well as the implications for understanding psychiatric disorders, in particular substance abuse, schizophrenia, and the potential antidepressant properties of ketamine, and comparisons with stimulants and other NMDA antagonists. Finally we identify future research needs.
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              KETOGENIC DIET AS A METABOLIC THERAPY FOR MOOD DISORDERS: EVIDENCE AND DEVELOPMENTS

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                Author and article information

                Contributors
                drcalabrese@innovativepsychiatry.com
                Journal
                Eat Weight Disord
                Eat Weight Disord
                Eating and Weight Disorders
                Springer International Publishing (Cham )
                1124-4909
                1590-1262
                23 August 2022
                23 August 2022
                2022
                : 27
                : 8
                : 3751-3757
                Affiliations
                [1 ]Innovative Psychiatry, South Windsor, CT USA
                [2 ]Internal Medicine and Addiction Medicine, Waban, MA USA
                [3 ]Ketogenic Diet Therapy, Elm Grove, WI USA
                [4 ]Clinical Peer Counselor, New York, NY USA
                [5 ]GRID grid.59734.3c, ISNI 0000 0001 0670 2351, Center of Excellence in Eating and Weight Disorders, Icahn School of Medicine at Mount Sinai, ; New York, NY USA
                [6 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Department of Psychiatry, , University of California San Diego, ; San Diego, CA USA
                Author information
                http://orcid.org/0000-0002-6590-3441
                Article
                1455
                10.1007/s40519-022-01455-x
                9803738
                35997954
                1cf3d329-4341-419b-a71c-ade25787ac7f
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 26 May 2022
                : 19 July 2022
                Funding
                Funded by: Homeostasis Therapeutics
                Categories
                Brief Report
                Custom metadata
                © Springer Nature Switzerland AG 2022

                anorexia nervosa,eating disorders,ketamine,ketamine treatment,keto diet,ketogenic diet

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