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Obesity is a chronic and highly prevalent medical condition associated with increased risk for the development of numerous and sometimes fatal diseases. Despite its severity, there are few anti-obesity agents available on the market. Although psychotropic agents are not approved for the treatment of obesity, they have been used by clinicians as a therapeutic tool in daily clinical practice. The purpose of this article is to review the rationale, as well as the evidence, for the potential use of these agents in obesity treatment. Evidence for the efficacy of psychotropic agents in obesity treatment comes from different sources. The first type of evidence is weight loss observed with treatment in clinical trials of patients with neuropsychiatric syndromes (e.g. mood disorders, epilepsy). A recent example of such findings is the weight reduction reported in clinical trials involving obese patients with binge eating disorder. While randomised, controlled trials specifically designed to investigate the weight loss properties of psychotropic agents in obese patients are the most appropriate source of evidence of anti-obesity action, such trials remain scarce. The most studied psychotropic agents in obesity trials are drugs used in the treatment of mood disorders, i.e. mainly antidepressants and antiepileptics. SSRIs (e.g. fluoxetine, sertraline and fluvoxamine) were amongst the first psychotropic agents investigated in the treatment of obesity. Additional data have also been published for other antidepressants (e.g. venlafaxine, citalopram and bupropion) and antiepileptics (e.g. topiramate and zonisamide). Based on the available data for the efficacy of psychotropic agents in obesity and other related conditions, SSRIs may be considered for the management of certain subgroups of obese individuals with comorbid conditions such as depression, binge eating disorder and type 2 diabetes mellitus. In addition, some newer agents, such as bupropion, topiramate and zonisamide, appear to be promising candidates for selective use in the treatment of obesity. However, further studies are needed to define their possible role as new pharmacological options in the treatment of obesity.
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PMID:Psychotropic drugs in the treatment of obesity: what promise? 1527 May 93

Adolescent and young women with type 1 diabetes mellitus demonstrate a more than random coincidence with bulimia nervosa. However, the prevalence of eating disorders that do not fulfil the criteria of bulimia nervosa is also raised in women of this age group yet without diabetes mellitus. The comorbidity of type 1 diabetes and an eating disorder poses a risk factor in the development of diabetic follow-up diseases. Patients with an eating disorder and type 1 diabetes are characterized by an insufficient metabolic control and the early development of diabetic complications such as a retinopathy. The binge eating disorder, according to research aspects initially a new eating disorder entity, may especially be observed in overweight and obesity. Even if a binge eating disorder in persons with a type 2 diabetes does not occur more frequently than in those metabolically healthy persons, it does depict a risk factor for an accelerated weight gain which as rule involves an increase of insulin resistance.
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PMID:[Eating disorders and diabetes mellitus]. 1694 95

Ancillary therapies for weight management, consisting mainly of diet and exercise programs that incorporate variable levels of lifestyle modification techniques, are frequently ineffective to achieve clinically meaningful weight loss and maintenance. Although pharmacological treatment of obesity is widely used in most countries, the number of available drugs is still very limited. The most widely used anti-obesity agents are sibutramine and orlistat, both available in clinical practice for about a decade. A large number of clinical trials have demonstrated that both agents are safe and well tolerated, with a level of efficacy in the moderate weight loss recommended by the most relevant clinical guidelines. Several studies have assessed the efficacy and safety of sibutramine and orlistat in adolescents and also for the treatment of some associated conditions in adults, including type 2 diabetes, polycystic ovary syndrome and binge eating disorder. The positive results of these studies suggest an expanding role for both agents, not only for the treatment of obesity, but also for associated conditions. After the efficacy of orlistat for the prevention of type 2 diabetes demonstrated in the XENDOS study, the results of SCOUT study are awaited for a better evaluation of sibutramine impact on cardiovascular outcomes.
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PMID:The first decade of sibutramine and orlistat: a reappraisal of their expanding roles in the treatment of obesity and associated conditions. 1946 19

Neurotrophins, particularly, NGF and BDNF are now well recognized to mediate a dizzying number of trophobiological effects, ranging from the Rita Levi-Montalcini's neurotrophic through immunotrophic to metabotrophic effects.These are implicated in the pathogenesis of various diseases including neuropsychiatric and cardiometabolic diseases, such as dementia, depression, type 2 diabetes and obesity that may express a common phenotype and coexistence. Recently, adipobiology (adiposcience) as become a focus of numerous studies showing that the adipose tissue is the body's largest endocrine organ producing multiple signaling proteins, including NGF and BDNF, all these dubbed adipokines. On the basis of our and other authors' evidence that low NGF and/or BDNF levels are found in cardiometabolic diseases (atherosclerosis, obesity, type 2 diabetes, metabolic syndrome), a hypothesis of a critical role of neuro-metabotrophic deficit in the pathogenesis of these diseases has been raised. Since NGF and BDNF also exerts various synaptotrophic effects involved in cognitive enhancement, this hypothesis might also be related to neuropsychiatric diseases such as dementia, depression, schizophrenia, autism, Rett syndrome, anorexia nervosa, and bulimia nervosa. Finally, NGF- and BDNF-based therapeutic approach, including ampakines, antidepressants, selective deacetylase inhibitors, statins, peroxisome proliferator-activated receptor gamma agonists, and "brain food" and calorie restriction, is outlined.
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PMID:NGF and BDNF: from nerves to adipose tissue, from neurokines to metabokines. 2006 8

An emerging literature has illuminated an important link between Type 2 diabetes mellitus (DM) and binge eating disorder (BED) within obese cohorts. However, prior work has not examined this relationship specifically in a weight loss surgery (WLS) sample or fully explored potential psychosocial factors associated with this co-occurrence. Therefore, the present investigation sought to identify socio-demographic (i.e. age, education, BMI, ethnicity, gender, age of obesity onset) and psychological (i.e. depressive symptoms, hedonic hunger/food locus of control beliefs, severity of binge eating-related cognitions) correlates of the co-occurrence of Type 2 DM and BED among bariatric surgery candidates. An archival sample of 488 patients seeking surgical treatment for clinical obesity completed a standard battery of pre-operative psychosocial measures. The presence of BED was evaluated using a semi-structured clinical interview based on the DSM-IV TR (APA, 2000) and was further corroborated by responses on the Questionnaire on Eating and Weight Patterns-Revised (QEWP-R; Spitzer, Yanovski, & Marcus, 1993). Results indicated that 8.2% of the sample was classified as having both Type 2 DM and BED concurrently. A multivariate logistic regression model revealed that in addition to other psychological (e.g., binge eating-related cognitions, hedonic hunger) and demographic variables (i.e. male gender), African American ethnicity (OR=3.3: 1.41-7.73) was a particularly robust indicator of comorbid status. Findings support and extend previous health disparity research urging greater attention to the needs of traditionally underserved, at-risk populations seeking treatment for obesity complicated by dysregulated eating and metabolism. Additionally, these preliminary results underscore the relevance of considering the potential benefits of providing quality comprehensive pre- and post-operative psychological care among bariatric patients towards optimizing both short- and long-term health and well-being.
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PMID:A comparative analysis of Type 2 diabetes and binge eating disorder in a bariatric sample. 2174 Oct 14

Binge eating disorder is one of the most frequent comorbid mental disorders associated with overweight and obesity. Binge eating disorder patients often suffer from other mental disorders and longitudinal studies indicate a continuous weight gain during the long-term course. As in other eating disorders gender is a risk factor, but the proportion of male binge eating disorder patients is surprisingly high.In young women with type 1 diabetes the prevalence of subclinical types of bulimia nervosa is increased. In addition, insulin purging as a characteristic compensatory behavior in young diabetic women poses a considerable problem. In patients with type 1 diabetes, disturbed eating and eating disorders are characterized by insufficient metabolic control and early development of late diabetic sequelae. Patients with type 2 diabetes are often overweight or obese. Binge eating disorder does not occur more frequently in patients with type 2 diabetes compared to healthy persons. However, the comorbidity of binge eating disorder and diabetes type 2 is associated with weight gain and insulin resistance. Especially in young diabetic patients a screening procedure for disturbed eating or eating disorders seems to be necessary. Comorbid patients should be offered psychotherapy.
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PMID:[Eating disorders associated with obesity and diabetes]. 2175 Sep 49

Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder characterized by irregular menses, hyperandrogenism, and polycystic ovaries. The prevalence of PCOS varies depending on which criteria are used to make the diagnosis, but is as high as 15%-20% when the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine criteria are used. Clinical manifestations include oligomenorrhea or amenorrhea, hirsutism, and frequently infertility. Risk factors for PCOS in adults includes type 1 diabetes, type 2 diabetes, and gestational diabetes. Insulin resistance affects 50%-70% of women with PCOS leading to a number of comorbidities including metabolic syndrome, hypertension, dyslipidemia, glucose intolerance, and diabetes. Studies show that women with PCOS are more likely to have increased coronary artery calcium scores and increased carotid intima-media thickness. Mental health disorders including depression, anxiety, bipolar disorder and binge eating disorder also occur more frequently in women with PCOS. Weight loss improves menstrual irregularities, symptoms of androgen excess, and infertility. Management of clinical manifestations of PCOS includes oral contraceptives for menstrual irregularities and hirsutism. Spironolactone and finasteride are used to treat symptoms of androgen excess. Treatment options for infertility include clomiphene, laparoscopic ovarian drilling, gonadotropins, and assisted reproductive technology. Recent data suggest that letrozole and metformin may play an important role in ovulation induction. Proper diagnosis and management of PCOS is essential to address patient concerns but also to prevent future metabolic, endocrine, psychiatric, and cardiovascular complications.
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PMID:Epidemiology, diagnosis, and management of polycystic ovary syndrome. 2437 99

Diabetes is associated with increased risk for eating disorders, various dependent on type of diabetes. Binge eating disorder is more common in patient with type 2 diabetes (T2DM). Whereas, intentional omission of insulin doses for the purpose of weight loss occurs mainly in patient with type 1 diabetes (T1DM), however, in some patients with type 2 diabetes omission of oral hypoglycemic drugs can be present. Risk factors for the development of eating disorders in patients with diabetes include: age, female gender, greater body weight, body image dissatisfaction, history of dieting and history of depression. Poor glycemic control, recurrent episodes of ketoacidosis or recurrent episodes of hypoglycemia, secondary to intentional insulin overdose, missed clinical appointments, dietary manipulation and low self-esteem should raise concern. The consequence of eating disorders or disordered eating patterns in patients with diabetes is poor glycemic control and hence higher possibility of complications such as nephropathy, retinopathy and premature death.
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PMID:Eating Disorders in children and adolescents with Type 1 and Type 2 Diabetes: prevalence, risk factors, warning signs. 2668 51

The objective of this review was to examine the evidentiary basis for binge eating disorder (BED) with reference to the Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5) diagnostic criteria for BED. A PubMed search restricted to titles and abstracts of English-language reviews, meta-analyses, clinical trials, randomized controlled trials, journal articles, and letters using human participants was conducted on August 7, 2015, using keywords that included "binge eating disorder," DSM-5, DSM-IV, guilt, shame, embarrassment, quantity, psychological, behavior, and "shape and weight concerns." Of the 257 retrieved publications, 60 publications were considered relevant to discussions related to DSM-5 diagnostic criteria and were included in the current review, and 20 additional references were also included on the basis of the authors' knowledge and/or on a review of the reference lists from relevant articles obtained through the literature search. Evidence supports the duration/frequency criterion for BED and the primary importance of loss of control and marked distress in identifying individuals with BED. Although overvaluation of shape/weight is not a diagnostic criterion, its relationship to the severity of BED psychopathology may identify a unique subset of individuals with BED. Additionally, individuals with BED often exhibit a clinical profile consisting of psychiatric (eg, mood, obsessive-compulsive, and impulsive disorders) and medical (eg, gastrointestinal symptoms, metabolic syndrome, and type 2 diabetes) comorbidities and behavioral profiles (eg, overconsumption of calories outside of a binge eating episode and emotional eating). Future revisions of the BED diagnostic criteria should consider the inclusion of BED subtypes, perhaps based on the overvaluation of shape/weight, and an evidence-based reassessment of severity criteria.
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PMID:Characteristics of binge eating disorder in relation to diagnostic criteria. 2762 31

Although first-line antidepressants offer therapeutic benefit, about 35% of depressed patients are not adequately treated, creating a large unmet medical need. These medicines mostly enhance the synaptic levels of serotonin and/or norepinephrine. Evidence from preclinical and clinical studies implicate dopamine hypofunction in the pathophysiology of depression. Triple reuptake inhibitors (TRIs), which elevate dopamine in addition to serotonin and norepinephrine, may demonstrate greater efficacy, with the reversal of anhedonia and improved tolerability. Medicinal chemistry efforts have resulted in more than 10 clinical candidates, although clinical candidates have failed to demonstrate superior efficacy compared to placebo or existing antidepressants. Hence, the successful development of future TRIs for depression will demand strong translational evidence, an optimal dosing regimen, and better tolerability. TRIs also hold therapeutic potential for other indications, with four candidates under clinical development for attention deficit hyperactivity disorder, binge eating disorder, cocaine addiction, obesity, and type 2 diabetes. Clinical studies have indicated a lower abuse potential for TRIs than psychostimulants.
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PMID:Triple Reuptake Inhibitors as Potential Therapeutics for Depression and Other Disorders: Design Paradigm and Developmental Challenges. 3161 18


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