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1.  Do Mortality Rates in Eating Disorders Change over Time? A Longitudinal Look at Anorexia Nervosa and Bulimia Nervosa 
The American journal of psychiatry  2013;170(8):917-925.
Objective
Although anorexia nervosa has a high mortality rate, our understanding of the timing and predictors of mortality in eating disorders is limited. The authors investigated mortality in a long-term study of patients with eating disorders.
Method
Beginning in 1987, 246 treatment-seeking women with anorexia nervosa or bulimia nervosa were interviewed every 6 months for a median of 9.5 years to obtain weekly ratings of eating disorder symptoms, comorbidity, treatment participation, and psychosocial functioning. From January 2007 to December 2010 (median follow-up of 20 years), vital status was ascertained with a National Death Index search.
Results
Sixteen deaths (6.5%) were recorded (lifetime anorexia nervosa, N=14; bulimia nervosa with no history of anorexia nervosa, N=2). The standardized mortality ratio was 4.37 [95% CI=2.4-7.3] for lifetime anorexia nervosa and 2.33 [95% CI=0.3-8.4] for bulimia nervosa with no history of anorexia nervosa. Risk of premature death among women with lifetime anorexia nervosa peaked within the first 10 years of follow-up resulting in a standardized mortality ratio of 7.7 [95% CI=3.7-14.2]. The standardized mortality ratio varied by duration of illness and was 3.2 [95% CI=0.9-8.3] for women with lifetime anorexia nervosa for 0-15 years (4/119 died), and 6.6 [95% CI=3.2-12.1] for women with lifetime anorexia nervosa for >15-30 years (10/67 died). Multivariate predictors of mortality included alcohol abuse (p<0.0001), low body mass index (p=0.0005), and poor social adjustment (p=0.0090).
Conclusions
These findings highlight the need for early identification and intervention and suggest that a long duration of illness, substance abuse, low weight, and/or poor psychosocial functioning raise the risk for mortality in anorexia nervosa.
doi:10.1176/appi.ajp.2013.12070868
PMCID: PMC4120076  PMID: 23771148
2.  Anorexia nervosa 
BMJ Clinical Evidence  2011;2011:1011.
Introduction
Anorexia nervosa is characterised by a low body mass index (BMI), fear of gaining weight, denial of current low weight and its impact on health, and amenorrhoea. Estimated prevalence is highest in teenage girls, and up to 0.7% of this age group may be affected. While most people with anorexia nervosa recover completely or partially, about 5% die of the condition, and 20% develop a chronic eating disorder. Young women with anorexia nervosa are at increased risk of bone fractures later in life.
Methods and outcomes
We conducted a systematic review, and aimed to answer the following clinical questions: What are the effects of treatments in anorexia nervosa? What are the effects of interventions to prevent or treat complications of anorexia nervosa? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 40 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: atypical antipsychotic drugs, benzodiazepines, cyproheptadine, inpatient/outpatient treatment setting, oestrogen treatment (HRT or oral contraceptives), older-generation antipsychotic drugs, psychotherapy, refeeding, selective serotonin reuptake inhibitors (SSRIs), and tricyclic antidepressants.
Key Points
Anorexia nervosa is characterised by a low body mass index (BMI), fear of gaining weight, denial of current low weight and its impact on health, and amenorrhoea. Estimated prevalence is highest in teenage girls, and the condition may affect up to 0.7% of this group.Anorexia nervosa is related to family, sociocultural, genetic, and other biological factors. Psychiatric and personality disorders such as depression, anxiety disorders, obsessive compulsive disorder, and perfectionism are commonly found in people who have anorexia nervosa.Most people with anorexia nervosa recover completely or partially, but about 5% die from the condition and 20% develop a chronic eating disorder.Young women with anorexia nervosa are at increased risk of fractures later in life.Population assessment indicates that risks to fertility may be overstated in those who reach a healthy BMI, but children born to mothers who have recovered from anorexia nervosa seem to have lower birth weights.
There is no strong RCT evidence that any treatments work well for anorexia nervosa. However, there is a gradual accumulation of evidence suggesting that early intervention is effective. Increasing evidence suggests that working with the family may also interrupt the development of a persistent form of the illness, when this work begins early in the disease.
Evidence on the benefits of psychotherapy is unclear.
Refeeding is a necessary and effective component of treatment, but is not sufficient alone. Very limited evidence from a quasi-experimental study suggests that a lenient approach to refeeding is as effective and more acceptable compared with a more strict approach.Refeeding may be as effective in an outpatient setting as during hospital admission.Nasogastric refeeding has been used to speed up weight gain in inpatient observational studies, although it is rarely studied in RCTs. Very limited RCT evidence suggests that adding nasogastric feeding to oral nutrition can increase weight gain and reduce relapse in the short term more than oral nutrition alone, but these gains are not maintained at 1 year post-discharge. Given ethical and medical concerns with tube feeding, this approach is encouraged with caution.Nutritional supplements, including zinc, have only limited evidence for their effectiveness, and additional evaluations of these measures are warranted.
We don't know whether inpatient or outpatient treatment is more effective in people with anorexia nervosa.
Limited evidence from small RCTs has not shown significant weight gain from SSRIs or tricyclic antidepressants, some of which may cause serious adverse effects. Tricyclic antidepressants may cause drowsiness, dry mouth, blurred vision, and a prolonged QT interval in people who have anorexia nervosa. SSRIs have not been shown to be beneficial, but the evidence remains very limited; in the 4 RCTs we found, conclusions were limited because of small trial size and high rates of withdrawal.
Older-generation antipsychotic drugs may prolong the QT interval, increasing the risk of ventricular tachycardia, torsades de pointes, and sudden death. Atypical antipsychotics have been evaluated for their potential role in reducing agitation and anxiety related to refeeding, as well as for potentially increasing appetite. Increasing observational data (case series) have suggested that they may decrease obsessiveness and agitation. However, further evidence from large, well-conducted RCTs is necessary to draw reliable conclusions. Newer atypical antipsychotics, in particular olanzapine, do not seem to be associated with the same cardiac risks as older-generation antipsychotic drugs, but the known association between olanzapine and weight gain may impact compliance in people with anorexia nervosa. However, further research needs to be done.
We found insufficient RCT evidence assessing benzodiazepines or cyproheptadine for treating anorexia nervosa.
Oestrogen treatment has been hypothesised to reduce the negative effects on bone mineral density associated with anorexia nervosa. However, three small RCTs have failed to demonstrate clinically relevant changes in bone mineral density after treatment with oestrogen either HRT or oral contraceptives), and these results are supported by 2-year longitudinal data, which found similar lack of improvement.
PMCID: PMC3275304  PMID: 21481284
3.  Treatment of anorexia nervosa with long-term risperidone in an outpatient setting: case study 
SpringerPlus  2014;3:706.
Introduction
There are currently few studies focusing on the efficacy of long-term atypical antipsychotics to treat anorexia nervosa in the pediatric population.
Case description
This case report follows the treatment of a 17 year-old female with anorexia nervosa over her four-year undergraduate career. After two years of multidisciplinary treatment, low-dose risperidone was initiated due to persistence of her disease. She expressed decreased rigidity around meal times, her weight improved and she had resumption of menses. She was compliant with treatment through graduation and maintained her weight gain.
Discussion & evaluation
Atypical antipsychotics are a treatment option in the management of anorexia nervosa. Risperidone has not been studied as frequently as olanzapine for eating disorders. Risperidone was chosen for its more favorable side effect profile and decreased cost to the patient. Previous studies on anorexia nervosa treatment have occurred during inpatient treatment and have limited follow-up due to patients’ refusal to initiate or maintain medication compliance. This case presents 17 months of outpatient data. The efficacy of risperidone therapy was evaluated with frequent weight checks, subjective decrease in rigidity, serial complete metabolic panels, and restoration of menses.
Conclusions
In this case report, an adolescent female treated with low-dose risperidone had decreased rigid thinking, weight gain and resolution of secondary amenorrhea without medication side effects. Therefore, the atypical antipsychotic risperidone may be an effective long-term outpatient treatment option for patients with anorexia nervosa.
doi:10.1186/2193-1801-3-706
PMCID: PMC4265638  PMID: 25525567
Anorexia nervosa; Risperidone; Secondary amenorrhea; Eating disorders; Outpatient treatment; Case report
4.  Long-Term Physiological Alterations and Recovery in a Mouse Model of Separation Associated with Time-Restricted Feeding: A Tool to Study Anorexia Nervosa Related Consequences 
PLoS ONE  2014;9(8):e103775.
Background
Anorexia nervosa is a primary psychiatric disorder, with non-negligible rates of mortality and morbidity. Some of the related alterations could participate in a vicious cycle limiting the recovery. Animal models mimicking various physiological alterations related to anorexia nervosa are necessary to provide better strategies of treatment.
Aim
To explore physiological alterations and recovery in a long-term mouse model mimicking numerous consequences of severe anorexia nervosa.
Methods
C57Bl/6 female mice were submitted to a separation-based anorexia protocol combining separation and time-restricted feeding for 10 weeks. Thereafter, mice were housed in standard conditions for 10 weeks. Body weight, food intake, body composition, plasma levels of leptin, adiponectin, IGF-1, blood levels of GH, reproductive function and glucose tolerance were followed. Gene expression of several markers of lipid and energy metabolism was assayed in adipose tissues.
Results
Mimicking what is observed in anorexia nervosa patients, and despite a food intake close to that of control mice, separation-based anorexia mice displayed marked alterations in body weight, fat mass, lean mass, bone mass acquisition, reproductive function, GH/IGF-1 axis, and leptinemia. mRNA levels of markers of lipogenesis, lipolysis, and the brown-like adipocyte lineage in subcutaneous adipose tissue were also changed. All these alterations were corrected during the recovery phase, except for the hypoleptinemia that persisted despite the full recovery of fat mass.
Conclusion
This study strongly supports the separation-based anorexia protocol as a valuable model of long-term negative energy balance state that closely mimics various symptoms observed in anorexia nervosa, including metabolic adaptations. Interestingly, during a recovery phase, mice showed a high capacity to normalize these parameters with the exception of plasma leptin levels. It will be interesting therefore to explore further the central and peripheral effects of the uncorrected hypoleptinemia during recovery from separation-based anorexia.
doi:10.1371/journal.pone.0103775
PMCID: PMC4121212  PMID: 25090643
5.  Remission of anorexia nervosa after thyroidectomy: A report of two cases with Graves' disease and anorexia nervosa 
Thyroid Research  2011;4:17.
We report two patients with anorexia nervosa and Graves' disease who received subtotal thyroidectomy for Graves' disease and concomitantly experienced remission from anorexia nervosa. Both were young women (aged 20 and 26) at the time of surgery. Both had well controlled thyroid function and eating behavior at the time of surgery. Both were followed for over five years without relapse of anorexia nervosa or hyperthyroidism. These cases suggest the existence of an endocrine factor originating from the thyroid gland that is involved in the pathogenesis of anorexia nervosa. Since patients of thyroidectomy can remain in good health with supplement of thyroxine alone, it can be hypothesized that this anorexigenic endocrine factor is an evolutionary relic not necessary for the normal function of humans and does not have physiological effects unless secreted beyond normal levels. Given that, it implies the existence of a creature in the animal kingdom for which such an anorexigenic hormone is essential for survival. Migrating birds eat beyond their caloric expenditure before migration and become anorexic for the duration of their flight. It is also known that their thyroid function is elevated during migration. The normal physiology of migration is a complex mechanism involving the hypothalamic, pituitary, thyroid, adrenal and reproductive hormones. The mechanism of disease, however, can be simpler. A review of the literature is presented that suggest a heretofore unreported thyroid hormone, which is involved in the regulation of migration behavior, may be the responsible factor behind anorexia nervosa.
doi:10.1186/1756-6614-4-17
PMCID: PMC3253671  PMID: 22128818
thyroid; anorexia nervosa; thyroidectomy; avian migration
6.  Reduced salience and default mode network activity in women with anorexia nervosa 
Background
The neurobiology of anorexia nervosa is poorly understood. Neuronal networks contributing to action selection, self-regulation and interoception could contribute to pathologic eating and body perception in people with anorexia nervosa. We tested the hypothesis that the salience network (SN) and default mode network (DMN) would show decreased intrinsic activity in women with anorexia nervosa and those who had recovered from the disease compared to controls. The basal ganglia (BGN) and sensorimotor networks (SMN) were also investigated.
Methods
Between January 2008 and January 2012, women with restricting-type anorexia nervosa, women who recovered from the disease and healthy control women completed functional magnetic resonance imaging during a conditioned stimulus task. Network activity was studied using independent component analysis.
Results
We studied 20 women with anorexia nervosa, 24 recovered women and 24 controls. Salience network activity in the anterior cingulate cortex was reduced in women with anorexia nervosa (p = 0.030; all results false-discovery rate–corrected) and recovered women (p = 0.039) compared to controls. Default mode network activity in the precuneus was reduced in women with anorexia compared to controls (p = 0.023). Sensorimotor network activity in the supplementary motor area (SMA; p = 0.008), and the left (p = 0.028) and right (p = 0.002) postcentral gyrus was reduced in women with anorexia compared to controls; SMN activity in the SMA (p = 0.019) and the right postcentral gyrus (p = 0.008) was reduced in women with anorexia compared to recovered women. There were no group differences in the BGN.
Limitations
Differences between patient and control populations (e.g., depression, anxiety, medication) are potential confounds, but were included as covariates.
Conclusion
Reduced SN activity in women with anorexia nervosa and recovered women could be a trait-related biomarker or illness remnant, altering the drive to approach food. The alterations in the DMN and SMN observed only in women with anorexia nervosa suggest state-dependent abnormalities that could be related to altered interoception and body image in these women when they are underweight but that remit following recovery.
doi:10.1503/jpn.130046
PMCID: PMC3997603  PMID: 24280181
7.  The MOSAIC study - comparison of the Maudsley Model of Treatment for Adults with Anorexia Nervosa (MANTRA) with Specialist Supportive Clinical Management (SSCM) in outpatients with anorexia nervosa or eating disorder not otherwise specified, anorexia nervosa type: study protocol for a randomized controlled trial 
Trials  2013;14:160.
Background
Anorexia nervosa (AN) is a biologically based serious mental disorder with high levels of mortality and disability, physical and psychological morbidity and impaired quality of life. AN is one of the leading causes of disease burden in terms of years of life lost through death or disability in young women. Psychotherapeutic interventions are the treatment of choice for AN, but the results of psychotherapy depend critically on the stage of the illness. The treatment response in adults with a chronic form of the illness is poor and drop-out from treatment is high. Despite the seriousness of the disorder the evidence-base for psychological treatment of adults with AN is extremely limited and there is no leading treatment. There is therefore an urgent need to develop more effective treatments for adults with AN. The aim of the Maudsley Outpatient Study of Treatments for Anorexia Nervosa and Related Conditions (MOSAIC) is to evaluate the efficacy and cost effectiveness of two outpatient treatments for adults with AN, Specialist Supportive Clinical Management (SSCM) and the Maudsley Model of Treatment for Adults with Anorexia Nervosa (MANTRA).
Methods/Design
138 patients meeting the inclusion criteria are randomly assigned to one of the two treatment groups (MANTRA or SSCM). All participants receive 20 once-weekly individual therapy sessions (with 10 extra weekly sessions for those who are severely ill) and four follow-up sessions with monthly spacing thereafter. There is also optional access to a dietician and extra sessions involving a family member or a close other. Body weight, eating disorder- related symptoms, neurocognitive and psychosocial measures, and service use data are measured during the course of treatment and across a one year follow up period. The primary outcome measure is body mass index (BMI) taken at twelve months after randomization.
Discussion
This multi-center study provides a large sample size, broad inclusion criteria and a follow-up period. However, the study has to contend with difficulties directly related to running a large multi-center randomized controlled trial and the psychopathology of AN. These issues are discussed.
Trial Registration
Current Controlled Trials ISRCTN67720902 - A Maudsley outpatient study of treatments for anorexia nervosa and related conditions.
doi:10.1186/1745-6215-14-160
PMCID: PMC3679869  PMID: 23721562
Anorexia nervosa; Eating disorder not otherwise specified; Outpatient treatment; Randomized controlled trial; Cost effectiveness
8.  Serum brain-derived neurotrophic factor and peripheral indicators of the serotonin system in underweight and weight-recovered adolescent girls and women with anorexia nervosa 
Background
Brain-derived neurotrophic factor (BDNF) mutant mice show hyperphagia and hyperleptinemia. Animal and cell-culture experiments suggest multiple interrelations between BDNF and the serotonin (5-HT) system. We studied serum BDNF in patients with anorexia nervosa and its associations with peripheral indicators of the 5-HT system. To control for secondary effects of acute malnutrition, we assessed acutely underweight patients with anorexia nervosa (acAN) in comparison to long-term weight-recovered patients with the disorder (recAN) and healthy controls.
Methods
We determined serum BDNF, platelet 5-HT content and platelet 5-HT uptake in 33 patients in the acAN group, 20 patients in the recAN group and 33 controls. Plasma leptin served as an indicator of malnutrition.
Results
Patients in the acAN group were aged 14–29 years and had a mean body mass index (BMI) of 14.9 (standard deviation [SD] 1.4) kg/m2. Those in the recAN group were aged 15–29 years and had a mean BMI of 20.5 (SD 1.3) kg/m2 and the controls were aged 15–26 years and had a BMI of 21.4 (SD 2.1) kg/m2. The mean serum BDNF levels were significantly increased in the recAN group compared with the acAN group (8820, SD 3074 v. 6161, SD 2885 pg/mL, U = 154.5, p = 0.001). There were no significant associations between BDNF and either platelet 5-HT content or platelet 5-HT uptake. Among patients with anorexia nervosa, we found significant positive linear relations between BDNF and BMI (r = 0.312, p = 0.023) and between BDNF and leptin (r = 0.365, p = 0.016).
Limitations
We measured the signal proteins under study in peripheral blood.
Conclusion
Serum BDNF levels in patients with anorexia nervosa depend on the state of illness and the degree of hypoleptinemia. Upregulation of BDNF in weight-recovered patients with anorexia nervosa could be part of a regenerative process after biochemical and molecular neuronal injury due to prolonged malnutrition. Associations between the BDNF and the 5-HT system in humans remain to be established.
PMCID: PMC2702450  PMID: 19568484
9.  THE ENDOCRINOPATHIES OF ANOREXIA NERVOSA 
Endocrine Practice  2008;14(8):1055-1063.
Objective
To describe the hormonal adaptations and alterations in anorexia nervosa.
Methods
We performed a PubMed search of the English-language literature related to the pathophysiology of the endocrine disorders observed in anorexia nervosa, and we describe a case to illustrate these findings.
Results
Anorexia nervosa is a devastating disease with a variety of endocrine manifestations. The effects of starvation are extensive and negatively affect the pituitary gland, thyroid gland, adrenal glands, gonads, and bones. Appetite is modulated by the neuroendocrine system, and characteristic patterns of leptin and ghrelin concentrations have been observed in anorexia nervosa. A thorough understanding of refeeding syndrome is imperative to nutrition rehabilitation in these patients to avoid devastating consequences. Although most endocrinopathies associated with anorexia nervosa reverse with recovery, short stature, osteoporosis, and infertility may be long-lasting complications. We describe a 20-year-old woman who presented with end-stage anorexia nervosa whose clinical course reflects the numerous complications caused by this disease.
Conclusions
The effects of severe malnutrition and subsequent refeeding are extensive in anorexia nervosa. Nutrition rehabilitation is the most appropriate treatment for these patients; however, it must be done cautiously.
PMCID: PMC3278909  PMID: 19095609
10.  Resting tachycardia, a warning sign in anorexia nervosa: case report 
Background
Among psychiatric disorders, anorexia nervosa has the highest mortality rate. During an exacerbation of this illness, patients frequently present with nonspecific symptoms. Upon hospitalization, anorexia nervosa patients are often markedly bradycardic, which may be an adaptive response to progressive weight loss and negative energy balance. When anorexia nervosa patients manifest tachycardia, even heart rates in the 80–90 bpm range, a supervening acute illness should be suspected.
Case presentation
A 52-year old woman with longstanding anorexia nervosa was hospitalized due to progressive leg pain, weakness, and fatigue accompanied by marked weight loss. On physical examination she was cachectic but in no apparent distress. She had fine lanugo-type hair over her face and arms with an erythematous rash noted on her palms and left lower extremity. Her blood pressure was 96/50 mm Hg and resting heart rate was 106 bpm though she appeared euvolemic. Laboratory tests revealed anemia, mild leukocytosis, and hypoalbuminemia. She was initially treated with enteral feedings for an exacerbation of anorexia nervosa, but increasing leukocytosis without fever and worsening left leg pain prompted the diagnosis of an indolent left lower extremity cellulitis. With antibiotic therapy her heart rate decreased to 45 bpm despite minimal restoration of body weight.
Conclusions
Bradycardia is a characteristic feature of anorexia nervosa particularly with significant weight loss. When anorexia nervosa patients present with nonspecific symptoms, resting tachycardia should prompt a search for potentially life-threatening conditions.
doi:10.1186/1471-2261-4-10
PMCID: PMC503388  PMID: 15257758
anorexia nervosa; bradycardia; tachycardia; malnutrition
11.  Psychiatrists' attitudes towards autonomy, best interests and compulsory treatment in anorexia nervosa: a questionnaire survey 
Background
The compulsory treatment of anorexia nervosa is a contentious issue. Research suggests that psychiatrists have a range of attitudes towards patients suffering from anorexia nervosa, and towards the use of compulsory treatment for the disorder.
Methods
A postal self-completed attitudinal questionnaire was sent to senior psychiatrists in the United Kingdom who were mostly general adult psychiatrists, child and adolescent psychiatrists, or psychiatrists with an interest in eating disorders.
Results
Respondents generally supported a role for compulsory measures under mental health legislation in the treatment of patients with anorexia nervosa. Compared to 'mild' anorexia nervosa, respondents generally were less likely to feel that patients with 'severe' anorexia nervosa were intentionally engaging in weight loss behaviours, were able to control their behaviours, wanted to get better, or were able to reason properly. However, eating disorder specialists were less likely than other psychiatrists to think that patients with 'mild' anorexia nervosa were choosing to engage in their behaviours or able to control their behaviours. Child and adolescent psychiatrists were more likely to have a positive view of the use of parental consent and compulsory treatment for an adolescent with anorexia nervosa. Three factors emerged from factor analysis of the responses named: 'Support for the powers of the Mental Health Act to protect from harm'; 'Primacy of best interests'; and 'Autonomy viewed as being preserved in anorexia nervosa'. Different scores on these factor scales were given in terms of type of specialist and gender.
Conclusion
In general, senior psychiatrists tend to support the use of compulsory treatment to protect the health of patients at risk and also to protect the welfare of patients in their best interests. In particular, eating disorder specialists tend to support the compulsory treatment of patients with anorexia nervosa independently of views about their decision-making capacity, while child and adolescent psychiatrists tend to support the treatment of patients with anorexia nervosa in their best interests where decision-making is impaired.
doi:10.1186/1753-2000-2-40
PMCID: PMC2649038  PMID: 19091113
12.  Long-term misuse of zopiclone in an alcohol dependent woman with a history of anorexia nervosa: a case report 
Introduction
The Z-drugs, zaleplon, zopiclone and zolpidem, are short-acting hypnotics which act at the same receptor as the benzodiazepines, but seemingly without the potential for misuse and the development of dependence of the older benzodiazepines. However, with increased prescribing of Z-drugs, reports of misuse and possible dependence began to appear in the literature, particularly in people with a history of substance misuse and comorbid psychiatric illness. Here we report the case of a woman with a history of chronic zopiclone use and anorexia nervosa, admitted for alcohol detoxification.
Case presentation
A 31-year old Caucasian British woman with a history of long-term zopiclone use and anorexia nervosa was admitted as an inpatient for a ten-day alcohol detoxification. Her weekly (four days out of seven) intake of alcohol was 180 units and her daily intake of zopiclone, 30 mg. Apart from a short period five years ago, she had been taking zopiclone for 13 years at daily doses of up to 90 mg. She admitted to using 'on top' of her prescribed medication, purchasing extra tablets from friends or receiving them gratis from her partner. After detoxification from alcohol and zopiclone, she was prescribed diazepam which she found ineffectual and voiced her intention of returning to zopiclone on leaving the hospital.
Conclusion
Zopiclone is generally regarded as safer than benzodiazepines, however, this particular individual, who was using high doses of zopiclone over many years, may provide further evidence of a risk of dependency when this drug is prescribed for substance users with a comorbid psychiatric illness.
doi:10.1186/1752-1947-4-403
PMCID: PMC3014964  PMID: 21143957
13.  Anorexia nervosa 
BMJ Clinical Evidence  2009;2009:1011.
Introduction
Anorexia nervosa is characterised by a low body mass index (BMI), fear of gaining weight, denial of current low weight and its impact on health, and amenorrhoea. Estimated prevalence is highest in teenage girls, and up to 0.7% of this age group may be affected. While most people with anorexia nervosa recover completely or partially, about 5% die of the condition, and 20% develop a chronic eating disorder. Young women with anorexia nervosa are at increased risk of bone fractures later in life.
Methods and outcomes
We conducted a systematic review which aimed to answer the following clinical questions: What are the effects of treatments for anorexia nervosa? What are the effects of interventions to prevent or treat complications of anorexia nervosa? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 40 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: anxiolytic drugs, cyproheptadine, inpatient/outpatient treatment setting, oestrogen treatment, psychotherapy, refeeding, selective serotonin reuptake inhibitors (SSRIs), and tricyclic antidepressants.
Key Points
Anorexia nervosa is characterised by a low BMI, fear of gaining weight, denial of current low weight and its impact on health, and amenorrhoea. Estimated prevalence is highest in teenage girls, and may affect up to 0.7% of this group.Anorexia nervosa is related to family, sociocultural, genetic, and other biological factors. Psychiatric and personality disorders such as depression, anxiety disorders, obsessive compulsive disorder, and perfectionism, are commonly found in people who have anorexia nervosa.Most people with anorexia nervosa recover completely or partially, but about 5% die from the condition and 20% develop a chronic eating disorder.Young women with anorexia nervosa are at increased risk of fractures later in life.
There is no strong research evidence that any treatments work well for anorexia nervosa. However, there is a gradual accumulation of evidence which suggests that early intervention is effective. Working with the family may also interrupt the development of a persistent form of the illness.
Evidence on the benefits of psychotherapy is unclear.
Refeeding is a necessary and effective component of treatment, but is not sufficient alone. Very limited evidence from a quasi-experimental study suggests that a lenient approach to refeeding is as effective and more acceptable compared with a more strict approach.Refeeding may be as effective in an outpatient setting as during hospital admission.Nasogastric feeding is rarely required and can lead to problems due to hypophosphataemia.Nutritional supplements, including zinc, have only limited evidence for their effectiveness, and additional evaluation of these measures are warranted.
Limited evidence from small RCTs has not shown significant weight gain from SSRIs or tricyclic antidepressants, some of which may cause serious adverse effects. Tricyclic antidepressants may cause drowsiness, dry mouth, blurred vision, and a prolonged QT interval in people who have anorexia nervosa. SSRIs have not been shown to be beneficial, but the evidence remains very limited; in the four RCTs we found, conclusions were limited due to small trial size and high withdrawal rates.
Anxiolytic drugs (mainly older generation antipsychotic drugs) may prolong the QT interval, increasing the risk of ventricular tachycardia, torsades de pointes, and sudden death. Atypical antipsychotics have been evaluated for their potential role in reducing agitation and anxiety related to refeeding, as well as for potentially increasing appetite. Weak observational evidence has suggested that they may decrease obsessiveness and agitation. However, we found no RCTs of sufficient quality on the effects of atypical antipsychotics, and further evidence from large, well-conducted RCTs is necessary to draw reliable conclusions. Some atypical antipsychotics do not appear to be associated with the same cardiac risks as older-generation antipsychotic drugs. However, further research needs to be done.
We found insufficient evidence assessing cyproheptadine for treating anorexia nervosa.
Oestrogen treatment has been hypothesized to reduce the negative effects on bone mineral density associated with anorexia nervosa. However, three small RCTs have failed to demonstrate significant changes in bone mineral density after treatment with oestrogen.
PMCID: PMC2907776  PMID: 19445758
14.  Stability of Neuropsychological Performance in Anorexia Nervosa 
Background
We investigated the stability of neuropsychological performance and eating disorder (EDO) symptoms before, immediately after, and 2 years after inpatient treatment. We also examined relationships between neuropsychological and EDO measures.
Methods
Sixteen women who were admitted for inpatient treatment of anorexia nervosa participated in three evaluations: (1) at admission to the hospital, (2) at discharge, and (3) at a follow-up exam approximately two years after discharge.
Results
Body mass index increased significantly from each testing session to the next. Endorsement of eating disorder symptoms was significantly decreased at discharge and at follow-up compared to admission. In terms of cognitive performance, total scores on a brief neuropsychological battery (RBANS) were significantly greater at follow-up than at admission. We found no relationships between EDO symptoms and cognitive function at follow-up.
Conclusions
The current findings suggest that EDO symptoms and cognitive performance in anorexia nervosa patients can show improvement as long as two years after hospitalization, but there is no evidence that EDO symptoms are related to neuropsychological performance at that time.
doi:10.1080/10401230701844836
PMCID: PMC3808087  PMID: 18297581
anorexia nervosa; neuropsychological functioning; body mass index
15.  Eating Disorders in Schizophrenia: Implications for Research and Management 
Objective. Despite evidence from case series, the comorbidity of eating disorders (EDs) with schizophrenia is poorly understood. This review aimed to assess the epidemiological and clinical characteristics of EDs in schizophrenia patients and to examine whether the management of EDs can be improved. Methods. A qualitative review of the published literature was performed using the following terms: “schizophrenia” in association with “eating disorders,” “anorexia nervosa,” “bulimia nervosa,” “binge eating disorder,” or “night eating syndrome.” Results. According to our literature review, there is a high prevalence of comorbidity between schizophrenia and EDs. EDs may occur together with or independent of psychotic symptoms in these patients. Binge eating disorders and night eating syndromes are frequently found in patients with schizophrenia, with a prevalence of approximately 10%. Anorexia nervosa seems to affect between 1 and 4% of schizophrenia patients. Psychopathological and neurobiological mechanisms, including effects of antipsychotic drugs, should be more extensively explored. Conclusions. The comorbidity of EDs in schizophrenia remains relatively unexplored. The clearest message of this review is the importance of screening for and assessment of comorbid EDs in schizophrenia patients. The management of EDs in schizophrenia requires a multidisciplinary approach to attain maximized health outcomes. For clinical practice, we propose some recommendations regarding patient-centered care.
doi:10.1155/2014/791573
PMCID: PMC4251071  PMID: 25485152
16.  Natural Course of Bulimia Nervosa and of Eating Disorder Not Otherwise Specified: 5-Year Prospective Study of Remissions, Relapses, and the Effects of Personality Disorder Psychopathology 
Objective
To examine prospectively the natural course of bulimia nervosa and eating disorder not otherwise specified (EDNOS) and to test for the effects of personality disorder psychopathology on remission and relapse.
Method
Subjects were 92 female patients with current bulimia nervosa (N = 23) or EDNOS (N = 69) at baseline enrollment in the Collaborative Longitudinal Personality Disorders Study. Axis I psychiatric disorders (including eating disorders) were assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Version, and personality disorders were assessed with the Diagnostic Interview for DSM-IV Personality Disorders (DIPD-IV). The course of eating disorders was assessed with the Longitudinal Interval Follow-Up Evaluation and the course of personality disorders with the Follow-Along version of the DIPD-IV at 6 and 12 months and then yearly through 60 months. The study was conducted from July 1996 through June 2005.
Results
Probability of remission by 60 months was 74% for bulimia nervosa and 83% for EDNOS, and probability of relapse among those with a remission was 47% for bulimia nervosa and 42% for EDNOS. Patients with and without personality disorders did not differ in probability of remission. Cox proportional hazards regression analyses revealed that bulimia nervosa and EDNOS did not differ significantly in time to remission and that personality disorder comorbidity did not significantly predict time to remission. Analyses using proportional hazards regression with time-varying covariates revealed that dimensional changes in personality disorders were minimally related to either remission or relapse in these eating disorders.
Conclusions
The 5-year natural course of bulimia nervosa and EDNOS differed little with both eating disorder categories showing similar patterns of remissions and relapses. These findings suggest the clinical significance of EDNOS and the need for further research on this most common but least studied eating disorder. The natural course of bulimia nervosa and EDNOS does not appear to be influenced significantly by the presence, severity, or time-varying changes of co-occurring personality disorder psychopathology.
PMCID: PMC2527481  PMID: 17503983
17.  The journey from opposition to recovery from eating disorders: multidisciplinary model integrating narrative counseling and motivational interviewing in traditional approaches 
Background
In the world of today’s of ever-briefer therapies and interventions, people often seem more interested in outcome than process. This paper focuses on the processes used by a multidisciplinary team in the journey from opposition to change to recovery from eating disorders. The approach outlined is most relevant to those with severe and enduring illness.
Methods
This paper describes a five-phase journey from eating-disorder disability and back to health as it occurs for patients in a community-based facility. This integrative model uses narrative and motivational interviewing counseling weaved into traditional approaches. It approaches illness from a transdiagnostic orientation, addressing the dynamics and needs demanded by the comorbidities and at the same time responding effectively in a way that reduces the influence of the eating disorder.
The treatment described involves a five-phase journey: Preliminary phase (choosing a shelter of understanding); Phase 1: from partial recognition to full acknowledgment; Phase 2: from acknowledgment to clear cognitive stance against the eating disorder; Phase 3: towards clear stance against the “patient” status; Phase 4: towards re-authoring life and regaining self-agency; Phase 5: towards recovery and maintenance.
Results
In a longitudinal study of patients with a severe and debilitating eating disorder treated with this approach. The drop-out rate was less than 10%. This was during the first two months of treatment for those diagnosed with bulimia nervosa, and this was higher than in those diagnosed with anorexia nervosa. At the end of treatment (15 months to 4 years later) 65% of those treated with anorexia nervosa and 81% of those treated with bulimia nervosa were either in a fully recovered state or in much improved. At the four-year follow-up, 68% of those diagnosed with anorexia nervosa and 83% of those diagnosed with bulimia nervosa were categorized as either fully recovered or much improved. All patients who completed the program were gainfully employed.
Conclusions
The collaborative work, which is the heart of the described model increases the patient’s and family’s ownership of treatment and outcome and strengthen the therapeutic bond, thus enhances recovery.
doi:10.1186/2050-2974-1-19
PMCID: PMC4081798  PMID: 24999400
Anorexia nervosa; Bulimia nervosa; Transdiagnostic model
18.  Inpatient Cognitive Behaviour Therapy for Anorexia Nervosa: A Randomized Controlled Trial 
Psychotherapy and Psychosomatics  2013;82(6):390-398.
Background
The aim of this study was to compare the immediate and longer-term effects of two cognitive behaviour therapy programmes for hospitalized patients with anorexia nervosa, one focused exclusively on the patients' eating disorder features and the other focused also on mood intolerance, clinical perfectionism, core low self-esteem or interpersonal difficulties. Both programmes were derived from enhanced cognitive behaviour therapy (CBT-E) for eating disorders.
Methods
Eighty consecutive patients with severe anorexia nervosa were randomized to the two inpatient CBT-E programmes, both of which involved 20 weeks of treatment (13 weeks as an inpatient and 7 as a day patient). The patients were then followed up over 12 months. The assessments were made blind to treatment condition.
Results
Eighty-one percent of the eligible patients accepted inpatient CBT-E, of whom 90% completed the 20 weeks of treatment. The patients in both programmes showed significant improvements in weight, eating disorder and general psychopathology. Deterioration after discharge did occur but it was not marked and it was restricted to the first 6 months. There were no statistically significant differences between the effects of the two programmes.
Conclusions
These findings suggest that both versions of inpatient CBT-E are well accepted by these severely ill patients and might be a viable and promising treatment for severe anorexia nervosa. There appears to be no benefit from using the more complex form of the treatment.
doi:10.1159/000350058
PMCID: PMC3884188  PMID: 24060628
Anorexia nervosa; Body mass index; Cognitive behaviour therapy; Eating disorders, diagnosis, therapy; Female; Follow-up studies; Humans; Inpatient treatment; Relapse

19.  Dysfunctional metacognition and drive for thinness in typical and atypical anorexia nervosa 
Background
Anorexia nervosa is complex and difficult to treat. In cognitive therapies the focus has been on cognitive content rather than process. Process-oriented therapies may modify the higher level cognitive processes of metacognition, reported as dysfunctional in adult anorexia nervosa. Their association with clinical features of anorexia nervosa, however, is unclear. With reclassification of anorexia nervosa by DSM-5 into typical and atypical groups, comparability of metacognition and drive for thinness across groups and relationships within groups is also unclear. Main objectives were to determine whether metacognitive factors differ across typical and atypical anorexia nervosa and a non-clinical community sample, and to explore a process model by determining whether drive for thinness is concurrently predicted by metacognitive factors.
Methods
Women receiving treatment for anorexia nervosa (n = 119) and non-clinical community participants (n = 100), aged between 18 and 46 years, completed the Eating Disorders Inventory (3rd Edition) and Metacognitions Questionnaire (Brief Version). Body Mass Index (BMI) of 18.5 kg/m2 differentiated between typical (n = 75) and atypical (n = 44) anorexia nervosa. Multivariate analyses of variance and regression analyses were conducted.
Results
Metacognitive profiles were similar in both typical and atypical anorexia nervosa and confirmed as more dysfunctional than in the non-clinical group. Drive for thinness was concurrently predicted in the typical patients by the metacognitive factors, positive beliefs about worry, and need to control thoughts; in the atypical patients by negative beliefs about worry and, inversely, by cognitive self-consciousness, and in the non-clinical group by cognitive self-consciousness.
Conclusions
Despite having a healthier weight, the atypical group was as severely affected by dysfunctional metacognitions and drive for thinness as the typical group. Because metacognition concurrently predicted drive for thinness in both groups, a role for process-oriented therapy in adults is suggested. Implications are discussed.
doi:10.1186/s40337-015-0060-4
PMCID: PMC4491244  PMID: 26146555
Anorexia nervosa; Atypical anorexia nervosa; Metacognition; Drive for thinness
20.  Psychosomatic syndromes and anorexia nervosa 
BMC Psychiatry  2013;13:14.
Background
In spite of the role of some psychosomatic factors as alexithymia, mood intolerance, and somatization in both pathogenesis and maintenance of anorexia nervosa (AN), few studies have investigated the prevalence of psychosomatic syndromes in AN. The aim of this study was to use the Diagnostic Criteria for Psychosomatic Research (DCPR) to assess psychosomatic syndromes in AN and to evaluate if psychosomatic syndromes could identify subgroups of AN patients.
Methods
108 AN inpatients (76 AN restricting subtype, AN-R, and 32 AN binge-purging subtype, AN-BP) were consecutively recruited and psychosomatic syndromes were diagnosed with the Structured Interview for DCPR. Participants were asked to complete psychometric tests: Body Shape Questionnaire, Beck Depression Inventory, Eating Disorder Inventory–2, and Temperament and Character Inventory. Data were submitted to cluster analysis.
Results
Illness denial (63%) and alexithymia (54.6%) resulted to be the most common syndromes in our sample. Cluster analysis identified three groups: moderate psychosomatic group (49%), somatization group (26%), and severe psychosomatic group (25%). The first group was mainly represented by AN-R patients reporting often only illness denial and alexithymia as DCPR syndromes. The second group showed more severe eating and depressive symptomatology and frequently DCPR syndromes of the somatization cluster. Thanatophobia DCPR syndrome was also represented in this group. The third group reported longer duration of illness and DCPR syndromes were highly represented; in particular, all patients were found to show the alexithymia DCPR syndrome.
Conclusions
These results highlight the need of a deep assessment of psychosomatic syndromes in AN. Psychosomatic syndromes correlated differently with both severity of eating symptomatology and duration of illness: therefore, DCPR could be effective to achieve tailored treatments.
doi:10.1186/1471-244X-13-14
PMCID: PMC3556145  PMID: 23302180
Anorexia nervosa; Eating disorders; Psychosomatic syndromes; Illness denial; Alexithymia
21.  Diagnostic Crossover in Anorexia Nervosa and Bulimia Nervosa: Implications for DSM-V 
The American journal of psychiatry  2008;165(2):245-250.
Objective
The Diagnostic and Statistical Manual of Mental Disorders (DSM) is designed primarily as a clinical tool. Yet high rates of diagnostic “crossover” among the anorexia nervosa subtypes and bulimia nervosa may reflect problems with the validity of the current diagnostic schema, thereby limiting its clinical utility. This study was designed to examine diagnostic crossover longitudinally in anorexia nervosa and bulimia nervosa to inform the validity of the DSM-IV-TR eating disorders classification system.
Method
A total of 216 women with a diagnosis of anorexia nervosa or bulimia nervosa were followed for 7 years; weekly eating disorder symptom data collected using the Eating Disorder Longitudinal Interval Follow-Up Examination allowed for diagnoses to be made throughout the follow-up period.
Results
Over 7 years, the majority of women with anorexia nervosa experienced diagnostic crossover: more than half crossed between the restricting and binge eating/purging anorexia nervosa subtypes over time; one-third crossed over to bulimia nervosa but were likely to relapse into anorexia nervosa. Women with bulimia nervosa were unlikely to cross over to anorexia nervosa.
Conclusions
These findings support the longitudinal distinction of anorexia nervosa and bulimia nervosa but do not support the anorexia nervosa subtyping schema.
doi:10.1176/appi.ajp.2007.07060951
PMCID: PMC3684068  PMID: 18198267
22.  The ANTOP study: focal psychodynamic psychotherapy, cognitive-behavioural therapy, and treatment-as-usual in outpatients with anorexia nervosa - a randomized controlled trial 
Trials  2009;10:23.
Background
Anorexia nervosa is a serious eating disorder leading to high morbidity and mortality as a result of both malnutrition and suicide. The seriousness of the disorder requires extensive knowledge of effective treatment options. However, evidence for treatment efficacy in this area is remarkably weak. A recent Cochrane review states that there is an urgent need for large, well-designed treatment studies for patients with anorexia nervosa. The aim of this particular multi-centre study is to evaluate the efficacy of two standardized outpatient treatments for patients with anorexia nervosa: focal psychodynamic (FPT) and cognitive behavioural therapy (CBT). Each therapeutic approach is compared to a "treatment-as-usual" control group.
Methods/Design
237 patients meeting eligibility criteria are randomly and evenly assigned to the three groups – two intervention groups (CBT and FPT) and one control group. The treatment period for each intervention group is 10 months, consisting of 40 sessions respectively. Body weight, eating disorder related symptoms, and variables of therapeutic alliance are measured during the course of treatment. Psychotherapy sessions are audiotaped for adherence monitoring. The treatment in the control group, both the dosage and type of therapy, is not regulated in the study protocol, but rather reflects the current practice of established outpatient care. The primary outcome measure is the body mass index (BMI) at the end of the treatment (10 months after randomization).
Discussion
The study design surmounts the disadvantages of previous studies in that it provides a randomized controlled design, a large sample size, adequate inclusion criteria, an adequate treatment protocol, and a clear separation of the treatment conditions in order to avoid contamination. Nevertheless, the study has to deal with difficulties specific to the psychopathology of anorexia nervosa. The treatment protocol allows for dealing with the typically occurring medical complications without dropping patients from the protocol. However, because patients are difficult to recruit and often ambivalent about treatment, a drop-out rate of 30% is assumed for sample size calculation. Due to the ethical problem of denying active treatment to patients with anorexia nervosa, the control group is defined as "treatment-as-usual".
Trial registration
Current Controlled Trials ISRCTN72809357
doi:10.1186/1745-6215-10-23
PMCID: PMC2683809  PMID: 19389245
23.  Psychotropic medication use at a private eating disorders treatment facility: A retrospective chart review and descriptive data analysis 
Background:
The extent of psychotropic medication use in patients with eating disorders worldwide is unknown.
Objectives:
The purposes of this study were to: (1) describe the extent and pattern of psychotropic medication use at a private treatment facility for patients with eating disorders and (2) describe patient characteristics and treatment outcomes at the facility.
Methods:
This retrospective chart review included data from a private treatment facility (inpatient or outpatient) for patients with eating disorders in the greater Los Angeles area. Data from all patients of any age who attended the facility between January 1, 2004, and January 1, 2005, and who met the criteria for anorexia nervosa (AN), bulimia nervosa (BN), or eating disorder not otherwise specified (ED NOS) defined in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision were included. Two investigators used a consistent chart-review method for recording clinical status, including treatment-related adverse effects and discharge status (improved, no change, or decompensated from admission). Improved was defined as meeting 1 or more of the following criteria: achieved ideal body weight, stabilized mood, decreased eating disorder symptoms (binge-purge, restrictive, or ritualistic behavior), eating disorder remission, or decreased suicidal ideation plus another improvement in this list.
Results:
Data from 60 patients were included (31 with AN, 28 with 13N, and I with ED NOS). Ages ranged from 12 to 47 years, and the mean duration of treatment was 35 days. Fifty-eight (96.7%) patients received a psychotropic agent; 35 (58.3%) patients were prescribed 2 or more agents concomitantly. Selective serotonin reuptake inhibitors (SSRls) were the most commonly prescribed class of psychotropic medication (86.7%), followed by antipsychotics (38.3%). Fluoxetine, escitalopram, and aripiprazole were the most commonly prescribed agents (41.7%, 28.3%, and 23.3%, respectively). A total of 63.3% of patients had a comorbid diagnosis of major depressive disorder, with 96.7% of these patients prescribed an antidepressant. At discharge, 51.6% of the inpatients and 37.9% of the outpatients had improved (AN, 52.6% and 33.3%, respectively; BN, 54.5% and 41.2%, respectively). Of the patients prescribed an SSRI, 40.4% had improved. In the inpatient setting, 35.5% of patients receiving an antipsychotic had improved, versus 6.9% in the outpatient setting.
Conclusions:
The results of this retrospective chart review and descriptive analysis of data from patients at a private eating disorders treatment facility in the United States suggest that psychotropics, particularly antidepressants and antipsychotics, were highly utilized, largely to treat comorbid symptoms. Fluoxetine, escitalopram, and aripiprazole were the most commonly prescribed agents. We observed that psychotropic medication selection was based on patient comorbidities and symptom expression and severity.
doi:10.1016/j.curtheres.2005.12.011
PMCID: PMC3997119  PMID: 24764595
psychotropic medication; anorexia nervosa; bulimia nervosa; eating disorder; antidepressant; antipsychotic
24.  “Fixing a heart”: the game of electrolytes in anorexia nervosa 
Nutrition Journal  2014;13:90.
Case
A 25-year-old woman with chronic anorexia nervosa and depression presented with sudden weakness and fatigue. Psychosocial history was notable for binge-starve cycles over the past year and a decline in overall well-being. Vitals on presentation were notable for hypothermia, hypotension, and bradycardia. Initial exam was significant for emaciation, lethargy, and lower extremity edema. Laboratory work-up revealed markedly elevated LFTs, hypoglycemia, thrombocytopenia and elevated INR and lipase. ECG showed sinus bradycardia with prolonged QTc. Ultrasound revealed normal liver and biliary tree. Serum acetaminophen, alcohol level, and urinary toxicology were unremarkable. Work up for infectious, autoimmune, and genetic causes of hepatitis was negative. Echocardiogram revealed left ventricular hypokinesis and EF 10-15%. Nutritional support was begun slowly, however electrolyte derangements began to manifest on hospital day 2, with hypophosphatemia, hypokalemia, hypocalcemia, and hypomagnesemia. Multiple medical and psychiatric disciplines were consulted, and aggressive electrolyte monitoring and repletion were done. The patient’s overall clinical status improved slowly during her hospital course. Her liver enzymes trended down, and her QTc interval eventually returned toward the normal range. Repeat echocardiogram following treatment revealed improvement of her EF to 40%.
Discussion
Anorexia nervosa is an eating disorder characterized by extremely low body weight, fear of gaining weight or distorted perception of body image, and amenorrhea. Anorexia can lead to life threatening medical complications, and thus constitutes a major challenge to manage. Central to the pathogenesis of the refeeding syndrome is a weakened cardiopulmonary system, electrolytes abnormalities, hepatic dysfunction, liver hypoperfusion and failure.
Conclusion
Given the clinical presentation, this patient likely presented on the brink of developing frank refeeding syndrome, with cardiac dysfunction and hypovolemia, leading to hepatic hypoperfusion and ischemic hepatitis. Subsequently, she developed electrolyte disturbances characteristic of refeeding syndrome, which were managed without major complication. Her hospital course is encouraging not only for her recovery, but for the collaboration of the different teams involved in her care, and it highlights the importance of a multidisciplinary approach to caring for patients with the potential dire complications of a complex psychiatric illness.
doi:10.1186/1475-2891-13-90
PMCID: PMC4168120  PMID: 25192814
25.  Systematic review of evidence for different treatment settings in anorexia nervosa 
World Journal of Psychiatry  2015;5(1):147-153.
AIM: To compare outcomes in anorexia nervosa (AN) in different treatment settings: inpatient, partial hospitalization and outpatient.
METHODS: Completed and published in the English language, randomized controlled trials comparing treatment in two or more settings or comparing different lengths of inpatient stay, were identified by database searches using terms “anorexia nervosa” and “treatment” dated to July 2014. Trials were assessed for risk of bias and quality according to the Cochrane handbook by two authors (Madden S and Hay P) Data were extracted on trial quality, participant features and setting, main outcomes and attrition.
RESULTS: Five studies were identified, two comparing inpatient treatment to outpatient treatment, one study comparing different lengths of inpatient treatment, one comparing inpatient treatment to day patient treatment and one comparing day patient treatment with outpatient treatment. There was no difference in treatment outcomes between the different treatment settings and different lengths of inpatient treatment. Both outpatient treatment and day patient treatment were significantly cheaper than inpatient treatment. Brief inpatient treatment followed by evidence based outpatient care was also cheaper than prolonged inpatient care for weight normalization also followed by evidence based outpatient care.
CONCLUSION: There is preliminary support for AN treatment in less restrictive settings but more research is needed to identify the optimum treatment setting for anorexia nervosa.
doi:10.5498/wjp.v5.i1.147
PMCID: PMC4369544  PMID: 25815264
Anorexia nervosa; Treatment; Inpatient; Outpatient; Day patient

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