Olanzapine treatment of an adolescent girl with anorexia nervosa

This case report presents a severe case of anorexia nervosa in a 15-year-old female adolescent. The patient suffered from extreme weight loss and agitation that required hospitalization in the Intensive Care Unit. The initial treatment consisted of fluoxetine management. Marked improvements, both in weight and psychological adjustment, were observed with the later addition of olanzapine. The findings reported here support previous findings that suggest the beneficial use of olanzapine in the treatment of anorexia nervosa.     

舒必利与奥氮平治疗神经性厌食症患者的对照研究

目的:比较舒必利联合帕罗西汀与奥氮平联合帕罗西汀治疗神经性厌食症的疗效与副反应差别。方法:分析57例(其中使用舒必利组25例,奥氮平组32例)住院神经性厌食症患者治疗8周前后的体重,体重指数,汉密尔顿焦虑量表(HAMA),汉密尔顿抑郁量表(HAMD)及副反应量表(TESS)的结果。结果:两组治疗8周后体重,体重指数及汉密尔顿焦虑量表、汉密尔顿抑郁量表总分均比入院时有明显改善。同时治疗8周后奥氮平组比舒必利组在改善体重及体重指数上要更加明显,两组间比较有统计学差异,而在HAMA、HAMD、TESS的比较上未见统计学差异。结论:舒必利联合帕罗西汀与奥氮平联合帕罗西汀均能有效改善神经性厌食症患者的临床症状,奥氮平联合帕罗西汀相对舒必利联合帕罗西汀而言改善体重及体重指数的效果更佳,两组在副反应上未见明显差异。     

Gastrointestinal disturbances in anorexia nervosa and bulimia nervosa

Disturbances in the functioning of the upper gastrointestinal (GI ) tract have been described in both Anorexia Nervosa (AN) and Bulimia Nervosa (BN). Patients with AN experience substantial delays in gastric emptying as well as constipation. These problems may give rise to significant medical complications and may contribute to increased difficulties with refeeding and weight restoration. Reported GI disturbances in BN include increased gastric capacity, diminished gastric relaxation, delayed gastric emptying, diminished release of cholecystokinin (CCK) and abnormalities of enteric autonomic function, all of which may play a role in perpetuation of the syndrome. This article reviews evidence for the most common disturbances of GI function in AN and BN and discusses potential GI targets for therapeutic intervention.     

Serotonin neurotransmission in anorexia nervosa

Patients with anorexia nervosa (AN) show extreme dieting weight loss, hyperactivity, depression/anxiety, self-control, and behavioral impulsivity. 5-Hydroxytryptamine (5-HT; serotonin) is involved in almost all the behavioral changes observed in AN patients. Both genetic and environmental factors contribute toward the pathogenesis of AN. It is a frequent disorder among adolescent girls and young women and starts as an attempt to lose weight to look beautiful and attractive. Failure to see the turning point when fasting becomes unreasonable leads to malnutrition and AN. Tryptophan, the precursor of serotonin and an essential amino acid, is only available in the diet. It is therefore likely that excessive diet restriction and malnutrition decrease brain serotonin stores because the precursor is less available to the rate-limiting enzyme of 5-HT biosynthesis, which normally exists unsaturated with its substrate. Evidence shows that diet restriction-induced exaggerated feedback control over 5-HT synthesis and the smaller availability of tryptophan decreases serotonin neurotransmission at postsynaptic sites, leading to hyperactivity, depression, and behavioral impulsivity. A compensatory upregulation of postsynaptic 5-HT-1A receptors and hypophagic serotonin receptors may be involved in anxiety and suppression of appetite. It is suggested that tryptophan supplementation may improve pharmacotherapy in AN.     

Dopamine in anorexia nervosa: a systematic review

Anorexia nervosa (AN) is a chronic relapsing psychiatric disorder with a largely unknown pathophysiology. Dopamine has been implicated in the pathophysiology of the disorder by preclinical and clinical evidence. Preclinical studies have examined two main characteristics of AN: reduction in food intake (diet restriction) and hyperactivity. Diet restriction has been associated with reduced dopamine levels in the hypothalamus, hippocampus, and the dorsal striatum. Animal hyperactivity following diet restriction has been linked to increased dopamine in the hypothalamus. Increased dopamine in the nucleus accumbens was associated with food administration, but not food expectation. Tyrosine and dopaminergic antagonists normalized anorexia-like behaviors in animal models of AN, but did not restore body weight. Clinical studies on the etiology of AN have produced contradictory findings. Cerebrospinal fluid concentrations of dopamine and its metabolites have been reported to be decreased or normal under conditions of low weight, whereas they tended to normalize when the weight was restored. Plasma and urinary levels of dopamine and its metabolites have been found to be normal, increased, and decreased. Neuroendocrine studies suggest that dopaminergic neurotransmission is increased in AN. However, recent neuroimaging studies lend support to the increase in binding of dopaminergic receptors in the striatum, which favors the opposite theory that intrasynaptic dopamine is indeed decreased. Genetic studies implicate dopamine D2 receptors, the dopamine transporter, and the enzyme COMT. There are promising results with respect to the use of atypical antipsychotics against symptoms of AN beyond weight gain, but further trials are required.     

Management of psychiatric comorbidity in anorexia nervosa and bulimia nervosa

The eating disorders anorexia nervosa and bulimia nervosa present with comorbidity in a number of important areas, including depression, bipolar disorder, anxiety disorders (obsessive-compulsive disorder, panic disorder, social anxiety disorder and other phobias, and post-traumatic stress disorder) and substance abuse. The most important principle of treating comorbidity in these conditions is the recognition of the effect of starvation and unstable eating on both the diagnosis and response to treatment of the comorbidity. This article reviews the identification of the most common areas of comorbidity and describes treatment approaches for these conditions. When it occurs, clinicians should treat comorbidity in patients with eating disorders in the usual fashion, but must remain aware that the disturbed eating itself will negatively affect response to treatment.     

Selective serotonin re-uptake inhibitors in anorexia nervosa

Anorexia nervosa (AN), one of the major eating disorders, is a primarily psychiatric illness affecting a number of adolescents and young adults. AN usually runs a chronic course and is associated with significant morbidity and mortality. Drug therapy has modest success in its treatment. Various pharmacotherapeutic agents are being tested, with variable success. Selective serotonin re-uptake inhibitors are the one class of drug that has been found to be effective in AN, especially in preventing relapse. This article provides an overview of the current literature on the role of selective serotonin re-uptake inhibitors in the treatment of AN.     

Selective serotonin re-uptake inhibitors in anorexia nervosa

Anorexia nervosa (AN), one of the major eating disorders, is a primarily psychiatric illness affecting a number of adolescents and young adults. AN usually runs a chronic course and is associated with significant morbidity and mortality. Drug therapy has modest success in its treatment. Various pharmacotherapeutic agents are being tested, with variable success. Selective serotonin re-uptake inhibitors are the one class of drug that has been found to be effective in AN, especially in preventing relapse. This article provides an overview of the current literature on the role of selective serotonin re-uptake inhibitors in the treatment of AN.     

Monoamine oxidase inhibitor therapy for anorexia nervosa and bulimia: a preliminary trial of isocarboxazid

In an open prospective clinical study, 14 female outpatients with anorexia nervosa or bulimia completed a 6-week trial of isocarboxazid, with a mean dose of 34 mg. The eight bulimic and six restrictive anorexic subjects did not show any significant differences in medication response. Ratings of depression and anxiety showed significant improvement after the fourth week. Significant improvement in eating behavior, as measured by the number of meals missed per day, was noted. For the bulimic subgroup, bingeing and vomiting showed a nonsignificant reduction, while the urge to binge was significantly reduced. There was no significant weight change in either group during the study, although the restrictive group had gained substantially at 6-month follow-up.     

Available pharmacological treatments for anorexia nervosa

Currently, no medications are approved by the FDA for the treatment of anorexia nervosa (AN). However, there are several promising pharmacological targets. Treatment includes a weight restoration and a weight maintenance phase and different pharmacological treatments may be useful in one phase, but not the other. Although cyproheptadine has some modest benefit during the weight restoration phase, it is not widely used. Fluoxetine administered during the weight maintenance phase decreases relapse rate. The medications currently being most widely studied are the atypical antipsychotics, particularly olanzapine. Emerging evidence suggests that some AN patients have psychotic symptoms that may respond to antipsychotic agents. There are promising case reports and open-label studies of the atypical antipsychotics, but as yet, no randomised, placebo-controlled, double-blind studies have been reported. Additional novel treatment approaches are urgently needed for this group of severely ill patients who have a high premature mortality rate.     

Available pharmacological treatments for anorexia nervosa

Currently, no medications are approved by the FDA for the treatment of anorexia nervosa (AN). However, there are several promising pharmacological targets. Treatment includes a weight restoration and a weight maintenance phase and different pharmacological treatments may be useful in one phase, but not the other. Although cyproheptadine has some modest benefit during the weight restoration phase, it is not widely used. Fluoxetine administered during the weight maintenance phase decreases relapse rate. The medications currently being most widely studied are the atypical antipsychotics, particularly olanzapine. Emerging evidence suggests that some AN patients have psychotic symptoms that may respond to antipsychotic agents. There are promising case reports and open-label studies of the atypical antipsychotics, but as yet, no randomised, placebo-controlled, double-blind studies have been reported. Additional novel treatment approaches are urgently needed for this group of severely ill patients who have a high premature mortality rate.     

The human genetics of anorexia nervosa

Anorexia nervosa is a severe eating disorder characterised by restricted eating, the relentless pursuit of thinness and obsessive fears of being fat. The involved risk factors are probably numerous, but the existence of a genetic vulnerability has been proposed for decades. The heritability in the broad sense is computed on the basis of aggregation studies, treated twin samples and twin studies from the general population. Many difficulties make this heritability estimation problematic, but the convergence of the results (from family studies and two types of twin studies) gives the most convincing evidence in favour of a major role of genetics in the vulnerability to anorexia nervosa, with a heritability around 70%. Regarding the analysis of candidate genes, the most frequently studied is the 5-HT_2A gene, with positive and negative results. We thus propose a meta-analysis showing that a large heterogeneity between samples exists, but the main effect of the −1438A allele persists even when extracting this contaminating effect (p=0.003). Furthermore, the absence of significant correlation between odds ratio and time after first publication of each sample, and size of each sample, is in accordance with the fact that the A allele is a risk factor. In order to explain the high heterogeneity between the nine studies yet performed, an alternative explanation such as a “modifying the phenotype” effect is proposed.