Anorexia nervosa versus hyperinsulinism: therapeutic effects of neuropharmacological manipulation

Abstract

Background:We have demonstrated that anorexia nervosa is underpinned by overwhelming adrenal sympathetic activity which abolishes the neural sympathetic branch of the peripheral autonomic nervous system. This physiological disorder is responsible for gastrointestinal hypomotility, hyperglycemia, raised systolic blood pressure, raised heart rate, and other neuroendocrine disorders. Therefore, we prescribed neuropharmacological therapy to reverse this central and autonomic nervous system disorder, in order to normalize the clinical and neuroendocrine profile. Methods: The study included 22 female patients with anorexia nervosa (10 restricted type, 12 binge-eating type) who received three months of treatment with amantadine 100 mg/day. We measured blood pressure, heart rate, and circulating neurotransmitters, (noradrenaline, adrenaline, dopamine, platelet serotonin, free plasma serotonin) during supine resting, one minute of orthostasis, and a five-minute exercise test before and after one, two, and three months of treatment with amantadine, a drug which abrogates adrenal sympathetic activity by acting at the C1(Ad) medullary nuclei responsible for this branch of the peripheral sympathetic activity. Results: We found the amantadine abolished symptoms of anorexia nervosa from the first oral dose onwards. Normalization of autonomic and cardiovascular parameters was demonstrated within the early days of therapy. Abrupt and sustained increases in the plasma noradrenaline:adrenaline ratio and disappearance of abnormal plasma glucose elevation were registered throughout the three-month duration of the trial. Significant and sustained increases in body weight were documented in all cases. No relapses were observed. Conclusion: We have confirmed our previously published findings showing that the anorexia nervosa syndrome depends on the hypomotility of the gastrointestinal tract plus hyperglycemia, both of which are triggered by adrenal sympathetic hyperactivity. The above neuroendocrine plus neuroautonomic and clinical disorders which underpinned anorexia nervosa were abruptly suppressed since the first oral dose of amantadine, a drug able to revert the C1(Ad) over A5(NA) pontomedullary predominance responsible for adrenal and neural sympathetic activity, respectively.

Therapeutic Potentials of Ketamine and Esketamine in Obsessive–Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature

“…The number and quality of studies regarding ketamine and ED is still in its infancy, although glutamatergic neurotransmission plays an important role in ED, particularly in Anorexia Nervosa (AN) [82,83]. After encouraging results with some NMDA modulators, such as the partial agonist D-cycloserine [84,85] and the NMDA-r antagonist amantadine [86], ketamine has been tested in ED, with the rationale of normalizing glutamatergic transmission. At present, the data regarding the use of ketamine and esketamine in subjects diagnosed with an ED are preliminary, limited and related to AN only.…”

Medication in AN: A Multidisciplinary Overview of Meta-Analyses and Systematic Reviews

“…The NMDA receptor antagonist amantadine was also used in a case series of 22 patients [100]. Amantadine administered 45 min before the main meal improved neuro-autonomic symptoms during the meal.…”

The Role of the Noradrenergic System in Eating Disorders: A Systematic Review

“…The same group [46] investigated variations in blood pressure, heart rate, and circulating neurotransmitters, (NE, adrenaline, DA, platelet serotonin -5-HT, free plasma 5-HT) during rest, orthostasis and exercise, after treatment with amantadine, a drug which abrogates adrenal sympathetic activity by acting at the C1(Ad) medullary nuclei responsible for this branch of the peripheral sympathetic activity. The study was conducted on a sample of 22 females with AN.…”