Anorexia Nervosa - Treatment with Cyproheptadine, Amitriptyline, Zinc, Lithium, DHEA, Amantadine.

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Anorexia nervosa. Treatment efficacy of cyproheptadine and amitriptyline
Abstract
Patients with anorexia nervosa have concurrent problems of emaciation and depression. Therefore, treatment with medications affecting both weight gain and depression seemed reasonable. Seventy-two anorectic patients were randomly assigned in a double-blind study to receive cyproheptadine hydrochloride, a weight-inducing drug, amitriptyline hydrochloride, a tricyclic antidepressant, or placebo. Overall, cyproheptadine had a marginal effect on decreasing the number of days necessary to achieve a normal weight. There was a differential drug effect present in the bulimic subgroups of the anorectic patients: cyproheptadine significantly increased treatment efficiency for the nonbulimic patients and significantly impaired treatment efficiency for the bulimic patients when compared with the amitriptyline- and placebo-treated groups. The differential cyproheptadine effect on the anorectic bulimic subgroups is the first pharmacologic evidence of the validity of these subgroups. Cyproheptadine had an anti-depressant effect demonstrated by a significant decrease in the Hamilton depression ratings.
https://pubmed.ncbi.nlm.nih.gov/3511877

Controlled trial of zinc supplementation in anorexia nervosa
Abstract
Zinc supplementation of anorexia nervosa (AN) patients has been reported to increase the weight gain of AN patients in open trials. In this randomized, double-blind, placebo-controlled trial 100 mg of zinc gluconate, or placebo, was given daily to 35 female AN inpatients until they achieved a 10% increase in body mass index (BMI). The rate of increase in BMI of the zinc supplemented group (n = 16) was twice that of the placebo group (n = 19), and this difference was statistically significant (p = .03). The use of zinc supplementation should be considered in the treatment of AN patients.
https://pubmed.ncbi.nlm.nih.gov/8199605/

A double-blind controlled trial of lithium carbonate primary anorexia nervosa
Abstract
In this 4-week, double-blind, parallel group study, eight young women with primary anorexia nervosa were evaluated on lithium carbonate, and eight patients were treated with placebo and served as a control. All patients participated in a behavior modification treatment program. The lithium-treated and placebo groups were comparable on nearly all findings measured at baseline (t tests), with no significant differences observed except for calories per day, percent fat composition of the daily calories, "interpersonal sensitivity" on the Hopkins Symptom Checklist-90 (HSCL-90), "self-care" on the Goldberg Anorectic Attitude Questionnaires, (GAAQ) and "manipulation of others" on the physician-rated Psychiatric Rating Scale (PRS). The data were analyzed using repeated measures analysis of covariance (ANCOVA) with the baseline measure as the covariate. Group differences appeared in the areas of "denial or minimization of illness" on the GAAQ, "selective appetite" on the PRS, and weight. Although the repeated measures ANCOVA for weight revealed a significant group-by-time interaction, indicating nonparallelism and invalidating the test for group differences, ANCOVAs performed for each individual time point showed greater weight gain in the lithium group at weeks 3 and 4.
https://pubmed.ncbi.nlm.nih.gov/6801096/

Dehydroepiandrosterone treatment effects on weight, bone density, bone metabolism and mood in women suffering from anorexia nervosa—a pilot study
Abstract
We investigated the effects of the administration of dehydroepiandrosterone (DHEA) on weight, bone metabolism, bone density and clinical mood symptoms in outpatient Anorexia Nervosa (AN) patients. AN patients (n=26) were double-blindly randomized to receive DHEA (100 mg) or placebo for 6 months. Outcome measures were bone mineral density (BMD) and bone mineral content (BMC) measured by dual energy X-ray absorptiometry (DXA) and metabolism indexes, steroid hormones, and mood and eating disorder symptoms measured at baseline and at the 3 and 6 months follow-up visits. Mood and eating disorder symptoms were assessed monthly by the Beck Depression Inventory, Eating Disorder Inventory and Clinical Global Improvement Scales. No treatment or treatment by time interaction was observed for any bone density measures. Deoxypiridinolyne (DPD) was positively correlated with weight (P=0.02). An increase in body mass index (BMI) in the DHEA group was significantly higher at 4 months compared to the control group (P=0.05). Improvement of mood was significantly correlated with weight only in the DHEA group. Despite a significant decrease in DPD, no improvement in bone mineral density was detected. However, patients treated with DHEA benefited from a significant increase in BMI, which was positively correlated with improvement in mood.
https://www.sciencedirect.com/science/article/abs/pii/S0165178112003642

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.
https://pubmed.ncbi.nlm.nih.gov/21445279/