Olanzapine use as an adjunctive treatment for hospitalized children with anorexia nervosa: case reports

OBJECTIVE: A recent case report suggested that olanzapine resulted in improved weight gain and maintenance, as well as decreased anxiety and agitation, for two hospitalized inpatients with anorexia nervosa (AN). However, a subsequent larger case study did not show a relationship between the use of olanzapine and rate of weight gain among a primarily adult population. The aim of this case report was to clinically examine the therapeutic benefit and tolerability of olanzapine as an adjunctive treatment for four children with AN in a pediatric inpatient setting. RESULTS: Olanzapine use was associated with considerable weight gain and maintenance, with an average rate of weight gain during hospitalization of 0.99 kg per week. In addition to weight gain, olanzapine was associated with a clinically notable decrease in levels of agitation and premeal anxiety and almost immediate improvement in sleep, general functioning, and overall compliance with treatment. Olanzapine was also well tolerated in these young patients. DISCUSSION: These case report findings warrant more controlled research, including randomized controlled studies, to better determine the therapeutic benefits and safety of olanzapine use in children with AN.     

Eating behavior among women with anorexia nervosa

BACKGROUND: Disturbed eating and severe caloric restriction are characteristic features of patients with anorexia nervosa (AN). Despite the importance of eating behavior in the presentation of AN, there have been relatively few objective laboratory studies of eating behavior among persons with eating disorders. OBJECTIVE: The purpose of the study was to obtain objective measures of eating behavior among patients with AN before and immediately after weight restoration and to compare those measures with measures among control subjects. DESIGN: Twelve patients hospitalized for AN and 12 control subjects participated in the study. Eleven of the 12 patients were retested at 90% of ideal body weight. RESULTS: The average meal consumption was 103.97 +/- 102.08 g for patients at low weight and 178.03 +/- 202.97 g after weight restoration (NS). Control subjects consumed significantly more than did AN patients at both time points, and the average meal size was 489.58 +/- 187.64 g. Patients showed significant decreases in psychological and eating-disordered symptoms after weight restoration. CONCLUSION: These data suggest that patients with AN show a persistent disturbance in eating behavior, despite the restoration of body weight and significant improvements in eating-disordered and psychological symptoms.     

Using the eating disorder examination to identify the specific psychopathology of binge eating disorder

OBJECTIVE: The clinical features of binge eating disorder (BED) are not well established. Therefore, a comprehensive assessment of the specific psychopathology of BED as compared to anorexia nervosa (AN) and bulimia nervosa (BN) is warranted. This comparison was the aim of the present study. METHOD: Detailed ratings from an investigator-based interview, the Eating Disorders Examination (EDE), were compared across three groups of female patients: those with BED, AN, and BN, as well as normal-weight and overweight control subjects. RESULTS: When comparing BED to AN and BN, patients with BED had lower levels of restraint, eating concerns comparable to AN patients but lower than BN patients, and weight and shape concerns comparable to BN patients but higher than AN patients. Significantly more eating disorder psychopathology was found for BED patients as compared to the overweight controls on all bar the EDE restraint subscale. On the majority of individual EDE items, BED patients' scores were similar to those of AN and BN patients, including importance of shape and weight in self-evaluation and preoccupation with shape and weight. No significant relationship was found between BED patients' degree of overweight and eating psychopathology. DISCUSSION: Our findings support the status of BED as an eating disorder and suggest that the elevated EDE scores reflect the combined impact of being objectively overweight and having disordered cognitions and behaviors about eating, shape, and weight.     

A randomized trial on the efficacy of a 2-month tube feeding regimen in anorexia nervosa: A 1-year follow-up study

BACKGROUND & AIMS: Despite the high mortality rate in malnourished anorexia nervosa (AN) patients, very few trials have prospectively studied the efficacy of tube feeding. METHODS: This open prospective study was conducted in malnourished AN patients, who were randomized in tube feeding (n=41) or control (n=40) groups during a 2-month period. Thereafter, body weight, body mass gain, energy intake, eating behavior and relapse rates were compared during a 1-year follow-up, using paired Student t-test and ANOVA. RESULTS: At the end of the 2-months period, weight gain was 39% higher in the tube feeding group than in the control group (194+/-14 vs 126+/-19g/day; P<0.01). The fat-free mass gain was greater in the tube-feeding group: 109+/-14 vs 61+/-17g/day (P<0.01). Energy intake was higher in the tube feeding group than in the control group (P<0.05), as well as the decrease in bingeing episodes (P<0.01). Most patients thought that CEN improved their eating disorder. After discharge, the relapse-free period was longer in the CEN group than in the control one: 34.3+/-8.2 weeks vs 26.8+/-7.5 weeks (P<0.05). CONCLUSION: CEN is helpful in malnourished AN patients for weight restoration, without hindrance on the eating behavior therapy nor inducing a more rapid relapse.     

Decreased thyroidal triiodothyronine secretion in patients with anorexia nervosa: influence of weight recovery

Basal thyroxin (T4), triiodothyronine (T3), and thyrotropin (TSH) concentrations were significantly lower before weight recovery in 10 patients with anorexia nervosa (AN) than they were in control subjects. After weight recovery, basal T4 and TSH levels were unchanged and significantly lower in AN patients than in control subjects. Basal T3 concentrations increased significantly after weight gain: however, concentrations remained lower than those in the control subjects. The maximum increase in T3 and T3 net secretory response to thyrotropin-releasing hormone (TRH), obtained before and after weight recovery, appeared significantly lower than that in control subjects: however, the increases in TSH responses were not different from those of control subjects. Thus, low T3 concentrations in AN patients may be due not only to impaired peripheral conversion of T4 to T3 associated with the altered nutritional state, but also to decreased thyroidal T3 secretion in response to endogenous TSH, which is indicative of hypothalamic-pituitary-thyroidal dysfunction.     

Weight change in treatment with olanzapine and a psychoeducational approach

This study assesses the efficacy of an educational and dietary approach in preventing olanzapine-induced weight gain. Eighteen patients affected by schizophrenic disorders were treated with olanzapine and weighed twice-weekly for 24 weeks. A psychoeducational intervention and referral to a nutritionist was introduced from the beginning of olanzapine treatment in 9 patients, and from the 9th week of therapy in 8 patients. Results showed that after 8 weeks of olanzapine treatment, weight gain was contained in the subjects receiving intervention unlike patients without preventive intervention (+0.99+/-3.34 kg vs. +2.96+/-3.08 kg; p<.03). At the end of the trial these patients partly shed their gain (-1.77 kg), presenting a final weight which was not significantly different from baseline (+1.19 kg). Subjects receiving the psychoeducational approach from the beginning were significantly heavier than at baseline (+3.4 kg). Poor dietary compliance correlated significantly with an increase in body weight, while higher mean dosages of olanzapine correlated with better weight-gain control.     

Research on energy expenditure in individuals with eating disorders: a review

OBJECTIVE: This study reviews the published research on energy expenditure in individuals with anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). METHOD: Individual studies are reviewed and their results summarized. RESULTS: The most consistent finding is evidence of reduction in resting energy expenditure (REE) in patients with AN, which increases with increased energy intake and body weight. Data regarding BN are inconsistent. Three available studies in subjects with BED have not found evidence of changes in energy expenditure corrected for lean body mass compared with obese non-binge eaters. DISCUSSION: The ability to reliably and cost-effectively measure REE may aid in the refeeding of patients with AN where REE is reduced. Changes in BN and BED subjects have yet to be identified consistently.     

Eating disorders, dieting, and the accuracy of self-reported weight

OBJECTIVE: This study investigated the accuracy of self-reported weight and height in individuals with an eating disorder (i.e., anorexia nervosa [AN] and bulimia nervosa [BN]) and in individuals without an eating disorder (i.e., dieters and nondieters). METHOD: Self-reported and measured weights and heights were obtained from the eating disorder sample (n = 81) and the college student sample (n = 163) and were compared within and between the groups. RESULTS: Eating disorder patients were extremely accurate at self-reporting their weight. However, there was a significant difference in accuracy between AN and BN patients. AN patients slightly overreported their weight, whereas BN patients slightly underreported their weight. Both dieters and nondieters significantly underreported their weight. However, dieters significantly underreported their weight to a greater degree than did the nondieters. DISCUSSION: The implications of these subgroup differences and their specificity to weight reporting are discussed with reference to the accuracy of self-reported height.     

Use of nutritional supplements to increase the efficacy of fluoxetine in the treatment of anorexia nervosa

OBJECTIVE: Selective serotonin reuptake inhibitor (SSRI) medication does not appear to be effective in ill, malnourished anorexia nervosa (AN) patients. However, it may be effective in preventing relapse after weight restoration. The purpose of this study was to determine whether nutritional supplements could potentiate the effects of fluoxetine in underweight AN subjects. METHOD: Twenty-six subjects with AN participated in a trial of fluoxetine. In a double-blind, placebo-controlled manner, subjects received either nutritional supplements or a nutritional placebo. The nutritional supplement included tryptophan (the precursor of serotonin), vitamins, minerals, and essential fatty acids believed to influence serotonin pathway function. RESULTS: There was no significant difference in weight gain between subjects treated with fluoxetine plus nutritional supplements versus fluoxetine plus a nutritional placebo. Moreover, there were no significant differences between groups on mean changes in anxiety or obsessive and compulsive symptoms. DISCUSSION: The results of this study suggest that supplement strategies are not a substitute for adequate nutrition and are ineffective in increasing the efficacy of fluoxetine in underweight AN subjects.     

Changes in weight and body image over time in women with eating disorders

BACKGROUND: This study examined the changes in body image and weight in young women with an adolescent eating disorder, relative to women without an eating disorder (noED). METHOD: Three diagnostic groups, anorexia nervosa (AN; n = 10), bulimia nervosa (BN; n = 27), and binge eating disorder (BED; n = 42) and three comparison groups (noED; n = 659 each) were compared on body mass index (BMI) and self-reported current body size, ideal body size, and weight dissatisfaction. Dependent variables were examined 2 and 1 year before the onset, the onset year, and 1 and 2 years after the onset of the eating disorder in a model that was adjusted for ethnicity and BMI. RESULTS: BMI was lower in the AN group at all time points except 2 years before onset. AN girls evidenced a significantly stronger relation between BMI and current self-ratings and weight dissatisfaction than noED girls. BMI did not differ between the BN group and the noED group. Girls with BN reported larger current body sizes and greater weight dissatisfaction across all time points. The BED group had higher BMI than the noED group across time. BED girls reported greater current body size ratings and weight dissatisfaction than the noED girls. Girls with AN, BN, or BED did not differ from the noED girls on body ideal ratings. DISCUSSION: Body weight seems to influence perception of body size more so for girls with AN than for noED girls. No support was found for an accelerated weight gain over time for BN. Weight may increase over time for the BED group relative to the noED group, but larger studies are needed. Across all three groups, ideal body size appears to be unrelated to diagnostic status. Rather, the risk for developing an eating disorder appears to arise from size overestimation and related weight dissatisfaction.     

Research on energy expenditure in individuals with eating disorders: a review

OBJECTIVE: This study reviews the published research on energy expenditure in individuals with anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). METHOD: Individual studies are reviewed and their results summarized. RESULTS: The most consistent finding is a reduction in resting energy expenditure (REE) in patients with AN, which increases with increased energy intake and body weight. Data regarding BN are inconsistent. Three available studies in subjects with BED have not found evidence of changes in energy expenditure corrected for lean body mass compared with obese non-binge eaters. DISCUSSION: The ability to measure REE reliably and cost-effectively may aid in the refeeding of patients with AN in whom REE is reduced. Changes in individuals with BN and BED have yet to be consistently identified.     

Weight variance associated with atypical neuroleptics in nursing home dementia patients

OBJECTIVE: Atypical antipsychotics have been reported to cause significant weight gain. This study examined potential weight gain associated with the use of olanzapine or risperidone. DESIGN: A retrospective chart review. SETTING: Three long-term care facilities. Participants: Dementia patients (n = 50) given olanzapine or risperidone for the management of noncognitive behavioral disturbances. Measurements: Weight changes over a 4-month period. RESULTS: Overall, patients in both groups lost weight over a 4-month period. Four (16%) of the risperidone patients and no olanzapine patients gained more than 5 pounds. CONCLUSION: Weight change does not seem to be a significant clinical issue for older dementia patients taking low doses of atypical neuroleptics.     

Cognitive behavioral therapy and fluoxetine as adjuncts to group behavioral therapy for binge eating disorder

OBJECTIVE: Although binge eating disorder is a common and distressing concomitant of obesity, it has not yet been established whether affected individuals presenting to behavioral weight control programs should receive specialized treatments to supplement standard treatment. This study was designed to examine the added benefit of two adjunctive interventions, individual cognitive behavioral therapy (CBT) and fluoxetine, offered in the context of group behavioral weight control treatment. RESEARCH METHODS AND PROCEDURES: One hundred sixteen overweight/obese women and men with binge eating disorder were all assigned to receive a 16-session group behavioral weight control treatment over 20 weeks. Simultaneously, subjects were randomly assigned to receive CBT+fluoxetine, CBT+placebo, fluoxetine, or placebo in a two-by-two factorial design. Outcome measures, assessed at the end of the 16-session acute treatment phase, included binge frequency, weight, and measures of eating-related and general psychopathology. RESULTS: Overall, subjects showed substantial improvement in binge eating and both general and eating-related psychopathology, but little weight loss. Subjects who received individual CBT improved more in binge frequency than did those not receiving CBT (p<0.001), and binge abstinence was significantly more common in subjects receiving CBT vs. those who did not (62% vs. 33%, p<0.001). Fluoxetine treatment was associated with greater reduction in depressive symptoms (p<0.05). The 54 subjects who achieved binge abstinence improved more on all measures than the 62 subjects who did not. In particular, these subjects lost, on average, 6.2 kg compared with a gain of 0.7 kg among non-abstainers. DISCUSSION: Adjunctive individual CBT results in significant additional binge reduction in obese binge eaters receiving standard behavioral weight control treatment.     

Alterations in endothelium-associated proteins and serum thyroid hormone concentrations in anorexia nervosa.

Plasma concentrations of endothelium-associated proteins (EAP) (plasma fibronectin (PFN), angiotensin-converting enzyme, factor VIII-related antigen (F VIII-R:Ag)) and tissue plasminogen activator and serum thyroid hormone concentrations were studied in nine patients with anorexia nervosa (AN), before and after weight gain. Before weight gain (-35.9 (SE 2.3)% of standard body-weight) PFN was significantly reduced and F VIII-R:Ag was significantly increased in AN patients compared with the concentrations in control subjects (211.5 (SE 14.9) v. 274.7 (SE 16.6) micrograms/ml, P < 0.05; 129.2 (SE 14.1) v. 88.2 (SE 9.7) %, P < 0.05 respectively). Serum triiodothyronine (T3) and free T3 levels were also significantly lower before weight gain in AN patients (0.85 (SE 0.07) v. 1.53 (SE 0.08) nmol/l, P < 0.001; 2.57 (SE 0.23) v. 5.31 (SE 0.34) pmol/l, P < 0.001 respectively), although serum thyroxine (T4), free T4, and thyrotropin concentrations were within the normal range throughout the study periods. Following weight gain, PFN and F VIII-R:Ag concentrations normalized as did the thyroid hormone levels. The incremental changes in PFN levels correlated significantly with those in serum thyroid hormone concentrations (T3, r 0.79, P < 0.01; free T3, r 0.84, P < 0.01). These findings suggest that PFN levels may be directly related to serum T3 concentrations in AN patients.     

Can steroid use be a precipitant in the development of an eating disorder?

OBJECTIVE: Corticosteroids have a wide range of clinical indications in the treatment of both acute and chronic medical illnesses, and weight gain is a well-documented side effect of their use. In this paper, we describe eight individuals with an eating disorder, which appeared following steroid administration for a medical condition. METHOD: These findings, support the possibility that the excessive weight gain resulting from steroid use can be a precipitating factor in the development of an eating disorder, particularly among female adolescents and young women who are preoccupied with their appearance and weight. RESULTS: Physicians caring for women receiving corticosteroids should therefore familiarize themselves with these patients' pre-morbid and current eating habits, as well as their weight, dieting and body image histories. DISCUSSION: The relevance of these cases for furthering our understanding of the development and treatment of eating disorder is also discussed.     

Insulinogenic index at 15 min as a marker of nutritional rehabilitation in anorexia nervosa

BACKGROUND: Insulin responses to the oral-glucose-tolerance test (OGTT) in anorexia nervosa (AN) are related to body weight and show various patterns. Although weight gain is a key indicator of a successful nutritional program, it is not a sufficiently accurate index for assessing nutritional status, especially in the periods of marked fear of obesity, because patients often manipulate body weight measurements. OBJECTIVE: The aim of this study was to determine the relation between insulin metabolism during the early phase of the OGTT and progress (weekly weight gain) during nutritional rehabilitation. DESIGN: Forty-eight inpatients with AN (25 AN restricting type and 23 AN bulimic type) underwent the OGTT, with additional blood sampling at 15 min, when energy intake reached 6694 kJ/d (1600 kcal/d). Thirteen healthy volunteers were also studied. To evaluate early-phase insulin metabolism, we calculated the insulinogenic index after 15 (II(15 min)) and 30 min. On the basis of weekly changes in body weight, the AN participants were divided into good (> or =0.5 kg) and poor (<0.5 kg) responders. RESULTS: Among the AN patients, 48% were poor responders. Analysis of variance showed significant differences in the II(15 min) values (P = 0.0005) and showed that II(15 min) values for good responders were significantly higher than those for the other groups. CONCLUSIONS: These findings suggest that a lack of progress in weight gain is frequently observed in AN and that II(15 min) values may be a useful marker with which to assess the weekly progress during nutritional rehabilitation.     

Body composition in early onset eating disorders

BACKGROUND: Body mass index (BMI) or equivalent weight for height indices are the most widely used measures of body composition in early onset and adolescent eating disorders. Although of value as screening instruments the limitation in disease states is their inability to discriminate fat and fat-free components of body weight. OBJECTIVE: To compare height-adjusted fat and fat-free components of body composition in children and young adolescents with different types of eating disorders with those of age matched reference children. DESIGN: Weight, height, triceps and subscapular skinfold thickness were measured in 172 children (aged 7-16 y) with eating disorders receiving specialist treatment. Fat mass index (FMI) and fat-free mass index (FFMI) were calculated using Slaughter's and Deurenberg's equations and normalisation for height. Using data from 157 normal children, representative of the UK 1990 growth reference data, reference curves for FMI and FFMI+/-2 s.d. were derived. Results for patient groups were superimposed on these reference curves. RESULTS: FMI and FFMI were both reduced in eating disorders associated with malnutrition, including anorexia nervosa (AN). AN subjects did not differ from other subjects with comparable degrees of malnutrition. Children with eating disorders of normal weight, such as bulimia nervosa and selective eating, did not differ significantly from reference children in their relative FM and FFM. CONCLUSIONS: FM and FFM merit independent consideration in disorders of malnutrition in children, rather than expressing data as percentage body fat or percentage BMI. The implications of loss of FFM on growth and development merit further investigation.     

Prevalence of thiamin deficiency in anorexia nervosa

OBJECTIVE: Deficiency of thiamin (vitamin B1) causes a range of neuropsychiatric symptoms that resemble those reported in patients with anorexia nervosa (AN) but the prevalence of thiamin deficiency in AN has not been reliably established. This study was designed to investigate the prevalence of thiamin deficiency in AN. METHOD: Thirty-seven patients attending a specialist eating disorders unit and meeting all or some of the DSM-IV criteria for AN were compared with 50 blood donor controls. All subjects underwent measurement of erythrocyte transketolase activation following the addition of thiamin pyrophosphate, the standard biochemical test for thiamin deficiency. Deficiency was defined as a result more than 2 SD above the mean of the control population. RESULTS: Fourteen patients (38%) had results in the deficient range; 7 (19%) met the most stringent published criterion for deficiency. Deficiency was not related to duration of eating restraint, frequency of vomiting, or alcohol consumption. DISCUSSION: Thiamin deficiency may account for some of the neuropsychiatric symptoms of AN and routine screening or supplementation may be indicated.     

Body fat redistribution after weight gain in women with anorexia nervosa

BACKGROUND: Body image distortions are a core feature of anorexia nervosa (AN). Increasing evidence suggests that the fat distribution immediately after weight restoration in patients with AN differs from the distribution typical of healthy adult women. OBJECTIVE: The purpose of this study was to assess body fat distribution before and shortly after normalization of weight in women with AN. DESIGN: Body composition and fat distribution were assessed by anthropometry, dual-energy X-ray absorptiometry, and whole-body magnetic resonance imaging in 29 women with AN before and after weight normalization and at a single time point in 15 female control subjects. Hormone concentrations were also evaluated in patients and control subjects. RESULTS: During approximately 10.1 +/- 2.9 wk (range: 4-17.3 wk) of treatment, patients with AN gained 12.2 +/- 3.6 kg, and refed weight (54.1 +/- 4.2 kg) did not differ significantly from that of control subjects (54.7 +/- 4.4 kg). Waist-to-hip circumference ratio (P < 0.006), total trunk fat (P < 0.003), visceral adipose tissue (P < 0.006), and intramuscular adipose tissue (P < 0.003) were significantly greater in the weight-recovered patients than in the control subjects. In contrast, after refeeding, total subcutaneous adipose tissue and skeletal muscle mass did not differ significantly between the patients and control subjects. In patients with AN, serum cortisol decreased and serum estradiol increased significantly with refeeding but not to control concentrations. CONCLUSIONS: In women with AN, normalization of weight in the short term is associated with an abnormal distribution of body fat. The implications of these findings for the long-term psychological and physical health of women with AN are unknown.     

Unveiling Metabolic Phenotype Alterations in Anorexia Nervosa through Metabolomics

Anorexia nervosa (AN) is a mental disorder characterized by an intense fear of weight gain that affects mainly young women. It courses with a negative body image leading to altered eating behaviors that have devastating physical, metabolic, and psychological consequences for the patients. Although its origin is postulated to be multifactorial, the etiology of AN remains unknown, and this increases the likelihood of chronification and relapsing. Thus, expanding the available knowledge on the pathophysiology of AN is of enormous interest. Metabolomics is proposed as a powerful tool for the elucidation of disease mechanisms and to provide new insights into the diagnosis, treatment, and prognosis of AN. A review of the literature related to studies of AN patients by employing metabolomic strategies to characterize the main alterations associated with the metabolic phenotype of AN during the last 10 years is described. The most common metabolic alterations are derived from chronic starvation, including amino acid, lipid, and carbohydrate disturbances. Nonetheless, recent findings have shifted the attention to gut-microbiota metabolites as possible factors contributing to AN development, progression, and maintenance. We have identified the areas of ongoing research in AN and propose further perspectives to improve our knowledge and understanding of this disease.