Synergy between ketamine and ketogenic diet in anorexia nervosa, and other neurobehavioral disorders.

Through serendipity, we observed an apparent synergy between adopting a ketogenic diet and receiving ketamine infusions that led to complete and durable remission in two patients with chronic enduring anorexia nervosa. Both patients had struggled with the disorder for over a decade. We offer a hypothesis, based on glutamate to explain this synergy, and hope it stimulates further research.

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

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.

Heart rate variability as a biomarker for anorexia nervosa: A review.

OBJECTIVE: Anorexia nervosa (AN) typically begins in early adolescence and other than weight status has few reliable biomarkers. Early diagnosis is a critical prognostic factor, but this can be clinically challenging. Heart rate variability (HRV), the beat-by-beat variance in heart rate (HR), may provide a unique assessment for the presence of AN because it has clinical utility as a biomarker of cardiac autonomic control in various populations (e.g., athletes, the aged, those with cardiovascular diseases, etc.). We present a review of the literature examining HRV in those with AN. METHOD: Relevant publications were selected from PubMed using the search terms 'anorexia nervosa AND (HR OR HRV)'. Twenty papers were selected and reviewed. RESULTS: The majority of studies suggest that those with AN have markedly and consistently elevated HRV compared to controls, even greater than among young athletes. However, no studies have explored HRV as a biomarker for AN. DISCUSSION: Future studies on HRV should elucidate its role as a diagnostic biomarker for AN as well as its responsiveness with serial measurement to track response rates and predict relapse.

Remission from Chronic Anorexia Nervosa With Ketogenic Diet and Ketamine: Case Report.

BACKGROUND: Chronic anorexia nervosa is a tragic disease with no known effective pharmacological or behavioral treatment. We report the case of a 29 year-old woman who struggled with severe and enduring anorexia nervosa for 15 years, and experienced a complete recovery following a novel treatment of adopting a ketogenic diet followed by ketamine infusions. Her remission has persisted for over 6 months. CASE PRESENTATION: At age 14.5, the patient embarked on an effort to "eat healthy." She quickly lost control of the dieting, developed associated compulsions and obsessions about food, body dissatisfaction, emotional lability, and lost nearly 13.6 kilograms (30 pounds). She was hospitalized for 6 weeks, and while she regained some weight, she did not attain full weight restoration. For 15 years, she continued to eat in a restrictive manner, exercise compulsively, and have intermittent periods of alcohol dependence. Nevertheless, she always hoped to get well, and at age 29, she began a novel treatment for anorexia nervosa. CONCLUSIONS: This is the first report of a ketogenic diet used specifically for the treatment of anorexia nervosa, followed by a short series of titrated IV ketamine infusions leading to complete remission of severe and enduring anorexia nervosa, with weight restoration, and sustained cessation of cognitive and behavioral symptoms, for 6 months. Although these treatments were used sequentially the relationship between these modalities, and possible synergy, is unclear, and deserves further study. Complete and sustained remission of chronic anorexia nervosa is quite rare, and the novel use of a ketogenic diet and IV ketamine treatment in this potentially lethal condition suggests avenues for further research, and hope for patients and their families.

Antihistamine agents and pitolisant might be useful for anorexia nervosa.

This hypothesis is that patients with anorexia nervosa (AN) demonstrate derangement in the histamine central nervous system. It might be possible to ameliorate these by careful use of histamine receptor antagonists targeting Histamine 1, 2, or 3 receptors. Histamine 3 receptors are exclusively present in the brain. Pitolisant is the only one agent currently available that targets these receptors. Pitolisant (brand name Wakix) was approved in the European Union, as a treatment for narcolepsy in March 2016.

Hypothesis: Clues From Mammalian Hibernation for Treating Patients With Anorexia Nervosa.

This hypothesis is that anorexia nervosa (AN) is a biologically driven disorder, and mammalian hibernation may offer clues to its pathogenesis. Using this approach, this hypothesis offers suggestions for employing heart rate variability as an early diagnostic test for AN; employing the ketogenic diet for refeeding patients, attending to omega 3:6 ratio of polyunsaturated fatty acids (PUFAs) in the refeeding diet; and exploring clinical trials of the endocannabinoid-like agent, palmitoylethanolamde for patients with AN. This hypothesis also explores the role of lipids and autoimmune phenomena in AN, and suggest a lipodomics study to search for antibodies in the serum on patients with AN.

Ketogenic diet and anorexia nervosa.

This hypothesis suggest that starvation-induced ketosis, which leads to a fundamental biochemical change in the metabolic fuel supply of the brain, is uniquely anxiolytic and rewarding to patients prone to AN. Ketosis can easily be replicated by a unique diet marked by high fat, moderate protein, and very low carbohydrate. This diet, known as a ketogenic diet (KGD) mimics starvation, thus allowing the patient to experience the anxiolytic state of ketosis, and yet avoid the morbidity of starvation.

Anorexia nervosa, seasonality, and polyunsaturated fatty acids.

Anorexia nervosa is a serious neurobehavioral disorder marked by semistarvation, extreme fear of weight gain, frequently hyperactivity, and low body temperature. The etiology remains unknown. We present a speculation that a primary causative factor is that polyunsaturated fatty acids are skewed to prevent oxidative damage in phospholipid membranes. This causes a change in the trade off of oxidation protection vs homeoviscous adaptation to lower temperatures, which sets off a metabolic cascade that leads to the rogue state of anorexia nervosa.

Pilot study employing heart rate variability biofeedback training to decrease anxiety in patients with eating disorders.

Heart rate variability (HRV) biofeedback, a technique which encourages slow meditative breathing, was offered to 25 in-patients with various eating disorder diagnoses-anorexia nervosa, bulimia nervosa and binge eating disorder. We found that this modality had no serious side effects, and was subjectively useful to most participants. An enhanced ability to generate highly coherent HRV patterns in patients with recent onset anorexia nervosa was observed.

Anorexia nervosa: a rogue hibernation?

Anorexia nervosa is a puzzling and often tragic disorder which causes the individual to self starve and hyper-exercise. We present a speculative analysis of the disorder which begins by acknowledging and accepting the adaptation to flee famine theory. This theory holds that anorexia nervosa results from activation of an archaic pathway that functioned well during human's nomadic past. We advance this idea by suggesting that the faulty signal indicating there is a famine, arises from misalignment of the circadian/circannual oscillations. Entry and exit from hibernation is dependent on these cycles, and we draw an analogy between hibernation and anorexia nervosa. We offer ideas for testing the hypothesis, and targeting these faulty signals.

Effects of electroencephalogram biofeedback with Asperger's syndrome.

This article reports the pilot study of electroencephalogram (EEG) biofeedback to improve focusing and decrease anxiety in 10 adolescent boys diagnosed with Asperger's syndrome attending a therapeutic day school. Five of the boys dropped out of the study before 12 sessions were completed. The analysis of pre- and post-intervention quantitative EEGs for the five students who completed the study showed a trend to "normalization", but did not reach statistical significance. All five boys who completed 24 sessions showed improved behavior as rated by parents and teachers, but other factors, such as maturation could not be ruled out as causes of the improvement. The challenges facing this research and proposals for further exploration are outlined.