Eating-disorders (EDs) consequences to human health are devastating, involving social, mental, emotional, physical and life-threatening aspects, concluding on impairment and death in cases of extreme anorexia nervosa. It also implies that people suffering an ED need to find psychiatric and psychological help as soon as possible to achieve a fully physical and emotional recovery. Unfortunately, to date, there is a crucial lack of efficient clinical treatment to these disorders. In this review, we present an overview concerning the actual pharmacological and psychological treatments, the knowledge of cells, circuits, neuropeptides, neuromodulators and hormones in the human brain- and other organs- underlying these disorders, the studies in animal models and, finally, the genetic approaches devoted to face this challenge. We will also discuss the need for new perspectives, avenues and strategies to be developed in order to pave the way to novel and more efficient therapeutics.

Premature infants and those with brain injury often suffer from feeding intolerance and vomiting in the first several years of life. Cyproheptadine is a medication with antihistaminergic, antiserotonergic and anticholinergic effects, thought to increase gastric accommodation. We aimed to retrospectively review our experience using cyproheptadine for feeding intolerance and/or vomiting in children under the age of three.

This is a retrospective chart review of 39 patients less than three years of age who were prescribed cyproheptadine for feeding intolerance or vomiting and had follow-up information available.

Starting dose ranged widely (from 0.069 to 0.825 mg/kg/day). Side effects such as sleepiness and constipation were rare. The medication had a significant positive effect, defined as resolution of vomiting, improved feeding tolerance or improved comfort with feeds, in 67% of children. An additional 28% showed possible improvement, defined as some improvement in vomiting or improvement in vomiting or feeding tolerance in conjunction with other changes in addition to cyproheptadine.

In our experience, cyproheptadine appears to be safe and effective in decreasing vomiting and feeding intolerance in children less than three years of age. A trial of cyproheptadine could be considered before invasive testing in infants with feeding issues.

Eating disorders, especially anorexia nervosa and bulimia nervosa have been classically described in young females in Western population. Recent research shows that they are also seen in developing countries including India. The classification of eating disorders has been expanded to include recently described conditions like binge eating disorder. Eating disorders have a multifactorial etiology. Genetic factor appear to play a major role. Recent advances in neurobiology have improved our understanding of these conditions and may possibly help us develop more effective treatments in future. Premorbid personality appears to play an important role, with differential predisposition for individual disorders. The role of cultural factors in the etiology of these conditions is debated. Culture may have a pathoplastic effect leading to non-conforming presentations like the non fat-phobic form of anorexia nervosa, which are commonly reported in developing countries. With rapid cultural transformation, the classical forms of these conditions are being described throughout the world. Diagnostic criteria have been modified to accommodate for these myriad presentations. Treatment of eating disorders can be quite challenging, given the dearth of established treatments and poor motivation/insight in these conditions. Nutritional rehabilitation and psychotherapy remains the mainstay of treatment, while pharmacotherapy may be helpful in specific situations.

Psychotic disorders and eating disorders sometimes occur in the same person, and sometimes, but not always, at the same time. This can cause diagnostic confusion and uncertainty about treatment. This paper examines seven ways in which symptoms of both conditions can co-exist. The literature on this topic consists to a large extent of case reports, so that firm conclusions cannot be drawn from their examination. There is no consistent sequence in the co-occurrence of the two conditions-eating disorders sometimes precede, and sometimes follow the onset of psychosis. The advent of the psychosis, and sometimes the treatment of the psychosis can cure the eating disorder, but it can sometimes aggravate it. Psychosis is not necessarily a mark of severity in the course of an eating disorder, and food refusal can occur independent of severity in psychotic illness, but it can be a cause of death. There is some genetic association and some overlap of physiologic, cognitive and brain structure deficits in the two types of disorder. The connection between the two, however, remains speculative. The area of comorbidity and overlapping symptoms in psychiatry requires more research. Clinical recommendations include attention to the different individual ways in which these two disparate conditions often overlap.

The aim of this study was to assess the efficacy and safety of cyproheptadine (CY) use in infants and young children with poor growth treated at our multidisciplinary pediatric feeding program, and to describe changes in their weight and feeding behaviors.

A retrospective chart review of children treated with CY from January 2007 to July 2011 was performed. Demographic data, medical diagnosis, adverse effects of the drug, and changes in mealtime behaviors were extracted from the patients' medical records. For each patient who received the CY, weight-for-age z scores (WtZ) were calculated before and during treatment. Repeated-measures mixed model was used to analyze the pattern of change in WtZ over time and between groups. Differences in mean WtZ were tested between patients regularly receiving CY and a naturally conceived comparison group.

Of the 127 patients in treatment owing to poor weight gain who received the CY, 82 took the medication regularly as prescribed in combination with our interventional program. For these patients, the majority of the parents (96%) reported a positive change in mealtime and feeding behaviors. A significant improvement in mean WtZ was observed after starting CY when compared with the WtZ before treatment for those patients regularly receiving the medication. This effect was independent of patients' age and/or presence of an underline medical problem. No significant differences in mean WtZ were observed over time within the comparison group.

In our experience, the use of CY in combination with a specialized multidisciplinary interventional program is a safe and effective therapy in infants and young children with low appetite and poor growth.

Recent research has modified both the conceptualization and treatment of eating disorders. New diagnostic criteria reducing the "not otherwise specified" category should facilitate the early recognition and treatment of anorexia nervosa (AN) and bulimia nervosa (BN). Technology-based studies identify AN and BN as "brain circuit" disorders; epidemiologic studies reveal that the narrow racial, ethnic and income profile of individuals no longer holds true for AN. The major organs affected long term-the brain and skeletal system-both respond to improved nutrition, with maintenance of body weight the best predictor of recovery. Twin studies have revealed gene x environment interactions, including both the external (social) and internal (pubertal) environments of boys and of girls. Family-based treatment has the best evidence base for effectiveness for younger patients. Medication plays a limited role in AN, but a major role in BN. Across diagnoses, the most important medicine is food.

Anorexia Nervosa (AN) has a devastating impact on the psychological and physical well being of affected individuals. There is an extensive body of literature on interventions in AN, however more studies are needed to establish which form of pharmacotherapy is effective. The few meta-analyses that have been done are based on one type of medication only. This article is the first to present data on three different, most commonly used, forms of pharmacotherapy. The primary objective of this meta-analysis was to create an overview and to determine the efficacy of three forms of pharmacotherapy (antidepressants, antipsychotics, hormonal therapy) compared to treatment with placebo in patients with AN.

A systematic literature search was performed to identify all randomized controlled intervention trials investigating the effectiveness of pharmacotherapy for AN within the following databases: PubMed, PsycINFO, Embase and Cochrane Library. In addition, 32 relevant reviews and meta-analyses were screened for additional intervention studies. A meta-analysis was performed on a total of 18 included studies (N = 869). Efficacy was measured in terms of weight gain or weight restoration.

The pooled effect sizes indicating the difference between antidepressants and placebo, and between antipsychotics and placebo on weight were not significant. Because of the small sample size no meta regression and subgroup analyses could be conducted. The pooled effect size indicating the difference between hormonal therapy and the placebo condition on weight (all weight measures) at post-treatment was 0.42 (95% CI: 0.11 ~ 0.73), which was significant. For hormonal therapy heterogeneity was high (I(2) = 64.70). No evidence for publication bias was found. Meta-regression analyses of the weeks of medication treatment (slope = -0.008) yielded a significant effect (p = 0.04).

In this study we found that hormonal therapy has a significantly larger effect on weight compared to placebo in the treatment of AN. However for these analyses heterogeneity was high, which means that these results have to be regarded with caution. We found that anti-depressants and antipsychotics had no significant effect on weight compared to placebo in the treatment of AN, although the power to detect significant effects was too low.

The eating disorders (DCA) are complex systemic diseases with high social impact, which tend to become chronic with significant medical and psychiatric comorbidities. The literature data showed that there is good evidence to suggest the use of SSRIs, particularly at high doses of fluoxetine, in the treatment of BN reducing both the crisis of binge that the phenomena compensates and reducing the episodes of binge in patients with BED in the short term. Also, the topiramate (an AED) showed a good effectiveness in reducing the frequency and magnitude of episodes of binge with body weight reduction, both in the BN that is in the therapy of BED. To date, modest data support the use of low doses of second-generation antipsychotics in an attempt to reduce the creation of polarized weight and body shapes, the obsessive component, and anxiety in patients with AN. Data in the literature on long-term drug treatment of eating disorders are still very modest. It is essential to remember that the pharmacotherapy has, however, a remarkable efficacy in treating psychiatric disorders that occur in comorbidity with eating disorders, such as mood disorders, anxiety, insomnia, and obsessive-compulsive personality disorders and behavior.

This article will review the treatment research literature on patients with anorexia nervosa. Perhaps somewhat surprisingly, the controlled treatment literature on this disorder is fairly limited. This is attributable to several factors, including the fact that many patients with anorexia nervosa are difficult to engage in treatment and unwilling to participate in randomized trials, and that many of these patients are so critically ill that they require a multiplicity of interventions and long-term therapy, creating design problems for randomized trials. Nonetheless, the extant literature will be reviewed, including pharmacologic and psychotherapeutic interventions in adolescents and adults. One point that needs to be addressed at the outset is the proper venue for the treatment of anorexia nervosa. Many patients, particularly those very low in weight, require in-patient and/or partial hospital treatment as the initial intervention. Although third-party payers are increasingly reluctant to pay for such interventions, they remain the treatments of choice for many anorectic patients. Another issue concerns acute treatment, focusing on weight gain, versus relapse prevention, focusing on weight maintenance and further work on anorectic psychopathology. Different studies have focused on different areas.

The paper presents a critical review (with search date 2010) of the major psychotropic medications assessed in eating disorders, namely antipsychotics, antidepressants, mood-stabilizing medications, anxiolytic and other agents. The evidence of efficacy of drug treatments is mostly weak or moderate. In addition, attrition rates are usually higher than for psychotherapies. However, there is support for use of antidepressants, particularly high-dose fluoxetine in bulimia nervosa, and anticonvulsants (topiramate) for binge-eating disorder. Low-dose antipsychotic medication may be clinically useful as adjunct treatment in acute anorexia, particularly where there is high anxiety and obsessive eating-related ruminations and failure to engage, but more trials are needed. Drug therapies such as topiramate and anti-obesity medication may aid weight loss in obese or overweight patients with binge-eating disorder; however, common or potentially serious adverse effects limit their use.

Anorexia nervosa (AN) has the highest mortality rate between psychiatric disorders, and evidence for managing it is still very limited. So far, pharmacological treatment has focused on a narrow range of drugs and only a few controlled studies have been performed. Furthermore, the studies have been of short duration and included a limited number of subjects, often heterogenic with regard to stage and acute nutritive status. Thus, novel approaches are urgently needed. Body weight homeostasis is tightly regulated throughout life. With the discovery of orexigenic and anorectic signals, an array of new molecular targets to control eating behavior has emerged. This review focuses on recent advances in three important signal systems: leptin, ghrelin, and endocannabinoids toward the identification of potential therapeutical breakthroughs in AN. Our review of the current literature shows that leptin may have therapeutic potentials in promoting restoration of menstrual cycles in weight restored patients, reducing motor restlessness in severely hyperactive patients, and preventing osteoporosis in chronic patients. Ghrelin and endocannabinoids exert orexigenic effects which may facilitate nutritional restoration. Leptin and endocannabinoids may exert antidepressive and anxiolytic effects. Finally, monitoring serum concentration of leptin may be useful in order to prevent refeeding syndrome.

To review the literature on the use of atypical antipsychotics in anorexia nervosa of children and adolescents and to present three case reports on quetiapine treatment of this subgroup.

Review of the literature and case report.

Several case reports and two small open-label trials, mainly in adults, observed beneficial effects of olanzapine on anorexic psychopathology. Only 16 case reports have been published on children and adolescents. Because of its lower propensity to induce weight gain quetiapine might be favourable with regard to patients' compliance. Our case reports revealed positive psychopathological effects and good tolerability of quetiapine in minors with severe anorexia nervosa. Careful titration and intense drug monitoring are recommended.

In a small subset of patients with severe, treatment- resistant anorexia nervosa, extreme weight phobia, delusional body image disturbances or severe hyperactivity might be considered as indications for atypical antipsychotics. However, controlled studies are needed.

The aim of this study was to assess dose-related steady-state serum concentrations of olanzapine (OLZ) and its metabolites N-desmethyl OLZ (DMO) and 2-hydroxymethyl OLZ (2-OH-OLZ) (assessed by high-performance liquid chromatography) in 122 child and adolescent psychiatric patients (age 16.9 +/- 2.2, range, 10-21 years; 74 males, 48 females) with a variety of diagnoses: schizophrenia group (n = 80); nonschizophrenia group (n = 29); anorexia nervosa (AN) group (n = 13). Median OLZ serum concentrations were 32.7 (range, 1-118; all patients), 37.7 (2-115; schizophrenia group), and 18.7 (1-63, AN group) ng/mL. The median OLZ concentration-to-dose (C/D) ratio (n = 122) was 2.6, with 90% of the distribution between 0.8 and 5.5 (ng/mL)/(mg/d). OLZ concentration was significantly correlated with DMO (r = 0.567; P < 0.0005) but not with 2-OH-OLZ (r = 0.122; P = 0.188). Daily OLZ dose was correlated with OLZ concentration in all (r = 0.684; P < 0.0005), schizophrenic (r = 0.542; P < 0.0005), and AN (r = 0.805; P = 0.001) patients, respectively. Patients aged less than 16 years displayed similar C/D for OLZ (P = 0.58) but higher C/D for DMO (P = 0.003) than those 16 years or older. AN patients received lower median OLZ doses (7.5; 5-15 mg) than schizophrenic patients (12.5; 2.5-40 mg), even after correcting for body mass index (P = 0.02). OLZ dose did not differ (P = 0.088) between smokers and nonsmokers, but smokers showed lower C/D for OLZ than nonsmokers (P = 0.008). C/D for OLZ was 38% higher (P = 0.041) under comedication with selective serotonin reuptake inhibitors when compared with OLZ monotherapy. Multiple linear regression analysis revealed that 46% of the variation of OLZ concentration can be explained by dose, diagnosis, age, sex, smoking, and comedication. The data are compared with the literature, and the relevance of therapeutic antipsychotic drug monitoring in previously sparsely investigated subgroups, such as children and adolescents or patients with AN, is emphasized.

Anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED) comprise the currently recognised eating disorders. Although distinct diagnostic entities, they share certain forms of comorbid psychopathology, particularly anxiety and mood disorders. BN and BED have been studied most intensively as targets for pharmacotherapy. The list of drugs tested in eating disorders is substantial; however, the number of therapeutic classes of medications tested in these conditions is relatively modest. Antidepressant medications, including tricyclic antidepressants, selective serotonin re-uptake inhibitors, as well as some of the novel antidepressants, have shown evidence of some therapeutic value in both BN and BED. Their efficacy in AN, however, has been disappointing. The pharmacological options for AN are very limited. The number of controlled trials that have been conducted is small, and the research that has been successfully completed has generally failed to demonstrate medication efficacy. Patients with BN typically show reduced binge eating and purging frequency in medication trials, but rarely attain abstinence. In BED, patients often measure the value of their medication therapy by its ability to stimulate weight loss, which is another area on which future pharmacotherapy may improve. Novel pharmacological interventions are needed for each of these conditions. Peptide hormones are increasingly being evaluated for eating disorder treatment, including ghrelin agonists, neuropeptide Y1 and -5 antagonists, orexin receptor antagonists, corticotropin-releasing factor receptor 2 antagonists, histamine 3 antagonists, melanocortin 4 receptor antagonists, beta3-adrenoceptor agonists, 5-hydroxytryptamine-2A antagonists and growth hormone agonists. Although these compounds are in early phases of clinical testing for eating disorder treatments, data from these studies will be instructive in the quest for effective pharmacotherapy for these conditions. An overview of the current pharmacotherapy options for eating disorders is presented with a discussion of the emerging potential treatments.

Athletes risk injuries and make personal sacrifices in their education, careers, and personal relationships in pursuit of excellence. Well-prepared athletes and their support teams take steps to minimize these risks. Since the 1980s, it has been apparent that development of an eating disorder is a risk associated with considerable morbidity and significant mortality, and with shorter careers characterized by inconsistency and recurrent injury. How likely is it that an athlete will develop an eating disorder? Who is at risk? Can eating disorders be prevented? How can eating disorders be identified? What are the consequences of developing an eating disorder? What can be done to help an athlete who has an eating disorder? This article attempts to answer these questions.