Refeeding syndrome and psychopharmacological interventions in children and adolescents with Anorexia Nervosa: a focus on olanzapine-related modifications of electrolyte balance.

This study aims to investigate the potential correlation between the use of olanzapine, a psychopharmacological intervention commonly prescribed in Anorexia Nervosa treatment, and the occurrence of Refeeding Syndrome. Despite the acknowledged nutritional and biochemical impacts of olanzapine, the literature lacks information regarding its specific association with Refeeding Syndrome onset in individuals with Anorexia Nervosa. This is a naturalistic, retrospective, observational study, reporting the occurrence of Refeeding Syndrome in children and adolescents with Anorexia Nervosa, treated or untreated with olanzapine. Dosages and serum levels of olanzapine were assessed for potential associations with the occurrence of Refeeding Syndrome and specific variations in Refeeding Syndrome-related electrolytes. Overall, 113 patients were enrolled, including 46 (41%) who developed a Refeeding Syndrome. Mild (87%), moderate (6.5%), and severe (6.5%) Refeeding Syndrome was described, at a current average intake of 1378 ± 289 kcal/day (39 ± 7.7 kcal/kg/die), frequently associated with nasogastric tube (39%) or parenteral (2.2%) nutrition. Individuals receiving olanzapine experienced a more positive phosphorus balance than those who did not (F(1,110) = 4.835, p = 0.030), but no difference in the occurrence of Refeeding Syndrome was documented. The mean prescribed doses and serum concentrations of olanzapine were comparable between Refeeding Syndrome and no-Refeeding Syndrome patients.    Conclusion: The present paper describes the occurrence of Refeeding Syndrome and its association with olanzapine prescriptions in children and adolescents with Anorexia Nervosa. Olanzapine was associated with a more positive phosphorus balance, but not with a different occurrence of Refeeding Syndrome. Further, longitudinal studies are required. What is Known: • Refeeding Syndrome (RS) is a critical complication during refeeding in malnourished patients, marked by electrolyte (phosphorus, magnesium, potassium) imbalances. • Olanzapine, an atypical antipsychotic with nutritional and biochemical impacts, is used in Anorexia Nervosa (AN) treatment, however data concerning its association with RS are lacking. What is New: • The study observed RS in 46/113 (41%) young patients with AN. • Olanzapine-treated individuals showed a higher improvement in serum phosphate levels than untreated ones, although no impact on the occurrence of Refeeding Syndrome was observed.

Omega-3 as an adjuvant in the treatment eating and psychological symptoms in patients with anorexia nervosa: a systematic review and meta-analyses.

BACKGROUND: This study was carried out to assess the effects of omega-3 supplementation as an adjunct treatment for eating and psychological symptoms in patients with anorexia nervosa. METHODS: We conducted a systematic review of the literature using the terms 'anorexia nervosa' AND 'Fatty Acids, Omega-3'. Five randomised controlled trials with a total of 144 participants, published between 2003 and 2022, were included. RESULTS: The effects of supplementation of omega-3 on anxiety were standardised mean difference (SMD) 0.79, 95% confidence interval (CI) -0.08 to 1.66; p = 0.08; I² = 3%; two studies, 33 participants; moderate quality of evidence. For depression, the supplementation of omega-3 was SMD: 0.22, 95% CI: -0.50 to 0.93; p = 0.18; I² = 45%; two studies, 33 participants; moderate quality of evidence. For obsessive-compulsive disorder, the supplementation of omega-3 was SMD: -0.22, 95% CI: -0.70 to 2.25; p = 0.36; I² = 0%; three studies, 32 participants; low quality of evidence. CONCLUSION: This research showed that regardless of dose, time or, if associated with other components, the use of omega-3 supplementations as an adjuvant treatment showed no evidence of effect in eating and psychological symptoms in patients with anorexia nervosa.

A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model.

Anorexia nervosa (AN) is a psychiatric illness with the highest mortality. Current treatment options have been limited to psychotherapy and nutritional support, with low efficacy and high relapse rates. Hypothalamic AgRP (agouti-related peptide) neurons that coexpress AGRP and neuropeptide Y (NPY) play a critical role in driving feeding while also modulating other complex behaviors. We have previously reported that genetic ablation of Tet3, which encodes a member of the TET family dioxygenases, specifically in AgRP neurons in mice, activates these neurons and increases the expression of AGRP, NPY, and the vesicular GABA transporter (VGAT), leading to hyperphagia and anxiolytic effects. Bobcat339 is a synthetic small molecule predicted to bind to the catalytic pockets of TET proteins. Here, we report that Bobcat339 is effective in mitigating AN and anxiety/depressive-like behaviors using a well-established mouse model of activity-based anorexia (ABA). We show that treating mice with Bobcat339 decreases TET3 expression in AgRP neurons and activates these neurons leading to increased feeding, decreased compulsive running, and diminished lethality in the ABA model. Mechanistically, Bobcat339 induces TET3 protein degradation while simultaneously stimulating the expression of AGRP, NPY, and VGAT in a TET3-dependent manner both in mouse and human neuronal cells, demonstrating a conserved, previously unsuspected mode of action of Bobcat339. Our findings suggest that Bobcat339 may potentially be a therapeutic for anorexia nervosa and stress-related disorders.

Ketamine and Zinc: Treatment of Anorexia Nervosa Via Dual NMDA Receptor Modulation.

Anorexia nervosa is a disorder associated with serious adverse health outcomes, for which there is currently considerable treatment ineffectiveness. Characterised by restrictive eating behaviours, distorted body image perceptions and excessive physical activity, there is growing recognition anorexia nervosa is associated with underlying dysfunction in excitatory and inhibitory neurometabolite metabolism and signalling. This narrative review critically explores the role of N-methyl-D-aspartate receptor-mediated excitatory and inhibitory neurometabolite dysfunction in anorexia nervosa and its associated biomarkers. The existing magnetic resonance spectroscopy literature in anorexia nervosa is reviewed and we outline the brain region-specific neurometabolite changes that have been reported and their connection to anorexia nervosa psychopathology. Considering the proposed role of dysfunctional neurotransmission in anorexia nervosa, the potential utility of zinc supplementation and sub-anaesthetic doses of ketamine in normalising this is discussed with reference to previous research in anorexia nervosa and other neuropsychiatric conditions. The rationale for future research to investigate the combined use of low-dose ketamine and zinc supplementation to potentially extend the therapeutic benefits in anorexia nervosa is subsequently explored and promising biological markers for assessing and potentially predicting treatment response are outlined.

Comment on Keeler et al. Ketamine as a Treatment for Anorexia Nervosa: A Narrative Review. Nutrients 2021, 13, 4158.

Anorexia Nervosa (AN) represents a difficult therapeutic challenge, with up to 4% prevalence among females and increasing incidence among youth [...].

Reply to Skokou, M. Comment on "Keeler et al. Ketamine as a Treatment for Anorexia Nervosa: A Narrative Review. Nutrients 2021, 13, 4158".

In response to our narrative review, which suggested the use of the glutamatergic n-methyl-D-aspartate (NMDA) receptor antagonist ketamine as a potential treatment for anorexia nervosa (AN) [...].

Dehydroepiandrosterone status and efficacy of dehydroepiandrosterone supplementation for bone health in anorexia nervosa: A systematic review and meta-analysis.

OBJECTIVE: This study was designed to determine the status of dehydroepiandrosterone (DHEA) in women with anorexia nervosa (AN) and to assess the efficacy of DHEA supplementation as a treatment for bone health in women with AN. METHOD: Studies were retrieved from the PubMed, Embase, Cochrane Library, MEDLINE, and Scopus databases from inception to February 14, 2022. Observational studies that compared serum DHEA levels between women with AN and healthy controls were included for meta-analysis, and randomized controlled trials (RCTs) that evaluated the effects of DHEA supplementation on bone mass were reviewed. RESULTS: Meta-analysis of 15 cross-sectional studies revealed that patients with AN had significantly elevated serum DHEA levels (mean difference (MD) = 311.63 ng/dl; 95% confidence interval (CI), 78.01-545.25) and reduced DHEAS levels (MD = -24.90 µg/dl; 95% CI, -41.72 to -8.07) compared with healthy controls. A systematic review of seven RCTs found that DHEA monotherapy does not improve bone mineral density (BMD) compared with placebo after adjusting for weight gain. While the combination of DHEA and conjugated oral contraceptives has led to increased bone strength and decreased bone loss, the beneficial effect appears to be limited to older adolescents and adults with closed physes. Potential detrimental effects on BMD were identified in younger adolescents with open physes in one study. DISCUSSION: Due to the lack of apparent benefit of DHEA in women with AN and its potential detrimental effect on BMD in young patients with AN, current evidence does not support the use of DHEA. PUBLIC SIGNIFICANCE: This study demonstrates that women with anorexia nervosa have abnormal levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS), which have been suggested by previous studies to play a role in the development of low bone density in this condition. However, current evidence does not support the use of DHEA as a treatment to preserve bone health in patients with anorexia nervosa given the lack of clear benefit following its use and also because of a potential detrimental effect on bone mineral density in young patients with anorexia nervosa.

OBJETIVO: Este estudio fue diseñado para determinar el estado de la dehidroepiandrosterona (DHEA) en mujeres con anorexia nerviosa (AN) y para evaluar la eficacia de la suplementación con DHEA como tratamiento para la salud ósea en mujeres con AN. MÉTODO: Los estudios se obtuvieron de las bases de datos PubMed, Embase, Cochrane library, MEDLINE y Scopus desde su inicio hasta el 14 de febrero de 2022. Se incluyeron estudios observacionales que compararon los niveles séricos de DHEA entre mujeres que padecen AN y controles sanos para el metanálisis, y se revisaron los ensayos controlados aleatorios (ECA) que evaluaron los efectos de la suplementación con DHEA sobre la masa ósea. RESULTADOS: El metanálisis de 15 estudios transversales reveló que los pacientes que padecen AN tenían niveles séricos significativamente elevados de DHEA (diferencia de medias [DM] = 311,63 ng/dL; intervalo de confianza [IC] del 95%, 78,01-545,25) y niveles reducidos de DHEAS (DM = -24,90 µg/dL; IC del 95%, -41,72 a -8,07) en comparación con los controles sanos. La revisión sistemática de siete ECA encontró que la monoterapia con DHEA no mejora la densidad mineral ósea (DMO) en comparación con placebo después de ajustar el aumento de peso. Si bien la combinación de DHEA y anticonceptivos orales conjugados ha llevado a un aumento de la fuerza ósea y una disminución de la pérdida ósea, el efecto beneficioso parece limitarse a adolescentes mayores y adultos con placas de crecimiento cerradas. En un estudio se identificaron posibles efectos perjudiciales sobre la DMO en adolescentes más jóvenes con placas de crecimiento abiertas. DISCUSIÓN: Debido a la falta de beneficio aparente de la DHEA en mujeres que padecen AN y su posible efecto perjudicial sobre la DMO en pacientes jóvenes que padecen AN, la evidencia actual no apoya el uso de la DHEA.

Treatment studies with cannabinoids in anorexia nervosa: a systematic review.

INTRODUCTION: Anorexia nervosa (AN) is a psychiatric disorder with a high mortality and unknown etiology, and effective treatment is lacking. For decades, cannabis has been known to cause physical effects on the human body, including increasing appetite, which may be beneficial in the treatment of AN. OBJECTIVE: To systematically review the literature for evidence of an effect of cannabinoids on (1) weight gain, and (2) other outcomes, in AN. METHOD: A systematic review was done using three databases Embase, PubMed and Psychinfo. The review was registered in PROSPERO with ID number CRD42019141293 and was done according to PRISMA guidelines. RESULTS: There were 1288 studies identified and after thorough review and exclusion of copies, 4 studies met the inclusion criteria. Three studies used the same AN population and utilized data from one original study, leaving only two original studies. Both of these were Randomized Controlled Trials that explored the effects of delta-9-tetrahydrocannabinol (Δ9-THC) or dronabinol in AN, whereof one study was properly designed and powered and showed a weight increase of an added 1 kg over 4 weeks over placebo. DISCUSSION AND CONCLUSION: There are few studies and the level of evidence is low. The only properly designed, low bias and highly powered study found a weight increasing effect of dronabinol in AN, while the other, using Δ9-THC at a high dose, found no effect and where the dose may have counteracted the weight gaining effects due to adverse events. More research on cannabinoids in anorexia nervosa is warranted, especially its effects on psychopathology. LEVEL OF EVIDENCE: Level I, systematic review.

Phosphatidylcholine Containing Long Chain Omega-3 Fatty Acids: a Treatment Adjunct for Patients with Anorexia Nervosa?

BACKGROUND: Anorexia nervosa (AN) is a serious mental disorder with a high mortality rate and often a chronic course. In contrast to many other common mental disorders, there is no drug therapy approved for AN. METHODS: We performed a narrative literature review to consider whether a choline-containing molecule, such as phosphatidylcholine (PC), with an omega (ω)-3 long chain polyunsaturated fatty acid (LCPUFA) could be a potential future medicinal treatment for AN. RESULTS: Choline and LCPUFAs have individually shown benefit for mental health. Case series and pilot studies suggest ω-3 LCPUFAs may be effective in eating disorders. However, pharmacodynamic and pharmacokinetic considerations suggest a greater benefit from the combination of both components. CONCLUSION: The combination of a choline-containing molecule with an ω-3 LCPUFA may be clinically effective and well tolerated. This idea is supported by the current literature on the role of inflammation, the microbiome, the gut-brain-axis, hormonal, neurotransmitter and intracellular signalling, and on the structure and fluidity of nerve cells membranes in patients with AN.

Anorexia nervosa, zinc deficiency and the glutamate system: The ketamine option.

Anorexia nervosa (AN) is a severe, biological brain disorder with significant medical risks and a tenacious development over time. Unfortunately, few treatments show efficacy in people with AN although numerous therapies including pharmacological have been explored. Zinc deficiency has been implicated in AN and zinc is important in a large range of processes in the brain. In particular, it is an allosteric modulator of NMDA receptors - the maintenance of zinc levels within a normal, narrow range is essential for glutamatergic functioning. Chronic zinc deficiency increases neuronal stores of calcium and reduces direct modulation of NMDA receptors which collectively lead to overactivation and upregulation of NMDA receptors. This may facilitate pathologically high levels of glutamate, calcium influx and subsequent excitotoxicity, which can disrupt synaptogenesis and synaptic plasticity. While studies of zinc supplementation in AN have shown some promise, the efficacy of this treatment is limited. This may be due to AN illness chronicity and the significant changes already made, as well as a reduced potency of zinc to inhibit NMDA receptors in a pathological state. Thus, we propose that the safe (at low doses) yet more potent NMDA receptor antagonist, ketamine, may act to normalise a perturbed glutamatergic system and increase synaptogenesis in the short term. This 'kickstart' via ketamine could then allow zinc supplementation and other forms of treatment to enhance recovery in AN.

Efficacy of fluoxetine for anorexia nervosa caused by chemotherapy in patients with cholangiocarcinoma.

BACKGROUND: Fluoxetine has been reported to treat anorexia nervosa (AN) caused by chemotherapy in patients with cholangiocarcinoma effectively. However, no study systematically investigated its efficacy and safety. Thus, this study will systematically assess its efficacy and safety for AN caused by chemotherapy in patients with cholangiocarcinoma. METHODS: A comprehensive literature search for relevant studies will be conducted from the following databases from inception to the present: MEDILINE, EMBASE, Cochrane Library, Web of Science, PSYCINFO, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All randomized controlled trials on assessing the efficacy and safety of fluoxetine for AN caused by chemotherapy in patients with cholangiocarcinoma will be considered for inclusion in this study. RevMan V.5.3 software will be used for risk of bias assessment and statistical analysis. RESULTS: This study will summarize the latest evidence of fluoxetine for AN caused by chemotherapy in patients with cholangiocarcinoma through assessing outcomes of weight, depression, anxiety, and quality of life. Additionally, any adverse events will also be analyzed. CONCLUSION: The findings of this study will provide most recent evidence of fluoxetine for AN caused by chemotherapy in patients with cholangiocarcinoma. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019131583.

Impact of Adrenal Hormone Supplementation on Bone Geometry in Growing Teens With Anorexia Nervosa.

PURPOSE: Adolescents with anorexia nervosa (AN) have decreased dehydroepiandrosterone (DHEA) and estrogen concentrations that may contribute to skeletal deficits. We sought to determine whether DHEA + estrogen replacement (ERT) prevented bone loss in young adolescents with AN. METHODS: We recruited females with AN (n = 70, ages 11-18 years) into a 12-month, randomized, double-blind placebo-controlled trial. Participants were randomized to oral micronized DHEA 50 mg + 20 mcg ethinyl estradiol/.1 mg levonorgestrel daily (n = 35) or placebo (n = 35). Outcomes included serial measures of bone mineral density (BMD) by dual-energy X-ray absorptiometry (total body, hip, spine) and peripheral quantitative computed tomography (pQCT; tibia). Magnetic resonance imaging of T1-weighted images of the left knee determined physeal status (open/closed). RESULTS: Sixty-two subjects completed the trial. Physeal closure status was the strongest predictor of aBMD changes. Among girls with open physes, those who received DHEA + ERT showed a decline in BMD Z-scores compared with those receiving placebo, whereas there was no effect in those with at least one closed physis. Treatment did not affect any pQCT measures, regardless of physeal closure status. CONCLUSIONS: Combined DHEA + ERT did not significantly improve dual-energy X-ray absorptiometry or pQCT BMD measurements in young adolescent girls with AN, in contrast to an earlier trial showing benefit in older adolescents and young women. In girls with open physes, the mean change in the placebo arm was greater than that of the DHEA + ERT group. We conclude that DHEA + ERT is ineffective for preserving bone health in growing young adolescents with AN at the dose and route of administration described in this report.

The perceived therapeutic benefits of complementary medicine in eating disorders.

OBJECTIVES: The purpose of this study was to investigate the perception of Complementary Medicines (CMs) in community women; to identify which CM approaches people perceived as the most beneficial; and the impact of Eating Disorder (ED) symptoms on one's perception of treatment. DESIGN & SETTING: Electronic and paper-based surveys were distributed to a pre-existing cohort of community women (n = 100) aged 18 years and over. The survey included questions about the perception of CMs' benefits in EDs regarding a vignette of a women with Anorexia Nervosa (AN), and whether CMs helped the participant's own personal health. MAIN OUTCOME MEASURE: The mental health literacy of women with regards to the recognition, evidence-based and CM treatment, and outcomes of a fictional person with AN. RESULTS: Exercise, yoga, meditation, relaxation, vitamins and minerals, massage and creative therapy were perceived as very helpful for someone with AN and for general health. Excluding meditation, there was no significant relationship between the levels of ED symptoms and perceived helpfulness of the therapies. Positive benefits were perceived for the use of CMs for AN. CONCLUSION: Considering the positive regard for these approaches, empirical studies are required to test their efficacy in the treatment of EDs.

Personalized polyunsaturated fatty acids as a potential adjunctive treatment for anorexia nervosa.

Anorexia nervosa (AN) is a complex psychiatric disorder with high morbidity and mortality rates. While many individuals make full recoveries, up to a third of patients develop a chronic, treatment-resistant form of the illness that leads to a premature death in 15-20% of those affected. There have been few advances in treatment, both in terms of psychological or pharmacologic treatment over the last 30 years. Food aversion is commonly cited by patients with AN as a barrier to normalizing eating and weight. Our group has a keen interest in examining factors that might allow this to be addressed, thus improving treatment outcomes through personalized dietary plans or nutritional supplementation related to underlying genetic status. We demonstrated that polyunsaturated fatty acids (PUFAs)-derived bioactive lipids (eicosanoids) are implicated in not only the risk of AN, but also with its comorbid psychopathology. Of interest, the differential postprandial omega 6-derived eicosanoid shift observed in AN highlights the possibility that the metabolism of PUFAs is an important mechanism underlying the profound food version, contributing to pathological food restriction in AN. A concise knowledge of the relationships among PUFAs, eicosanoids, and AN clinical course and psychopathology could be the key to developing personalized nutritional rehabilitative treatments for those suffering from AN. This paper provides a comprehensive overview of the literature on PUFAs in AN. We also selectively reviewed the clinical benefits PUFA treatments exert in other psychiatric diseases, on weight and appetite regulation, and for resolution of inflammation, all of which are relevant in the disease course and outcome of AN. We propose that personalized PUFA formulation be developed and tested as a novel adjunctive treatment for patients with AN. We hypothesize that with personalized PUFA formulation, food aversion and anxiety about eating will decrease while mood, dietary behavior, and weight restoration will improve in AN, leading to improvements in the overall treatment outcome.

2-Arachidonoylglycerol as a possible treatment for anorexia nervosa in animal model in mice.

We have investigated the effects of 0.001mg/kg 2-arachidonoylglycerol (2-AG) administered in combination with compounds present in the body alongside 2-AG like 2-palmitoylglycerol and 2-linoleylglycerol (also termed "entourage"), on cognitive function,food intake, and neurotransmitter levels in the hippocampus and hypothalamus of mice under diet restriction. Young female Sabra mice were treated with vehicle, 2-AG, 2-AG+entourage, 2-AG+entourage+5-(4-Chlorophenyl)-1-(2,4-dichloro-phenyl)- 4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (SR141716A, a CB1 antagonist) and SR141716A. The mice were fed for 2.5h a day for 14days. Cognitive function was evaluated by the eight arm maze test, and neurotransmitter (norepinephrine, dopamine, L-DOPA and serotonin) levels were measured in the hippocampus and hypothalamus by high-performance liquid chromatography-electrochemical detection. Food intake was increased by 2-AG and, to an even greater extent, by 2-AG+entourage. SR141716A reversed the effect of 2-AG+entourage. The administration of 2-AG+entourage improved cognitive function compared to the vehicle mice, and this improvement was blocked by SR141716A. 2-AG+entourage-treated mice showed an increase in norepinephrine (NE), dopamine and L-DOPA levels in the hippocampus. SR141716A normalized NE and L-DOPA levels. There were no significant changes in hypothalamic neurotransmitter levels. The use of very low doses of the endocannabinoid 2-AG+entourage can improve cognitive function by elevating norepinephrine and L-DOPA levels in the hippocampus, without cannabinomimetic side effects. These findings may have implications for cognitive enhancement in anorexia nervosa.

Improving therapeutics in anorexia nervosa with tryptophan.

A growing body of evidence suggests that our diet is an important contributing factor in the development, management and prevention of a number of psychiatric illnesses. Tryptophan, an essential amino acid, is the sole precursor of neurotransmitter 5-hydroxytryptamine (5-HT; serotonin). Administration of tryptophan can boost serotonin neurotransmission to produce therapeutically important effects in serotonin deficiency disorders. Anorexia nervosa (AN) an eating disorder associated with high levels of psychiatric comorbidity including psychosis, hyperactivity, depression and anxiety has highest lethality of all psychiatric illnesses. Evidence suggests that excessive dieting and food restriction can decrease brain tryptophan and serotonin in AN patients to precipitate depression, psychosis and hyperactivity. There are currently no FDA approved pharmacological treatments available for AN patients; antidepressants and antipsychotics, largely used to treat associated psychiatric comorbidities are also not very effective. The aim of this non-systematic review article is to evaluate and document a potential importance of tryptophan supplementation in improving therapeutics in AN patients.

A Double Blind, Randomized Cross-Over Trial of Tyrosine Treatment on Cognitive Function and Psychological Parameters in Severe Hospitalized Anorexia Nervosa Patients.

BACKGROUND: Anorexia nervosa (AN) is characterized by self-induced malnutrition, affecting body image, mood, cognition and survival. Tyrosine, an essential amino acid is the precursor of catecholamines. The use of tyrosine to treat AN is based on experiments on diet restricted mice, in which it increased food consumption, improved cognitive function and elevated brain catecholamines. We evaluated the effect of oral tyrosine administration on the cognition and emotional state of patients with AN. We hypothesized that tyrosine may improve cognitive function without changing body weight, thus "kick-start" nutritional rehabilitation. METHODS: 19 female hospitalized patients with chronic AN were supplemented with L-tyrosine (100 mg/kg/day)/ placebo capsules for a three-week period in a double blind, randomized, cross-over study. Participants were evaluated cognitively and psychologically. RESULTS: Tyrosine shortened reaction time and test duration in memory tasks and improved depressive mood. No side effects were noted with the use of tyrosine. CONCLUSIONS: Tyrosine may improve cognitive function and psychological traits associated with AN.

Inpatient treatment for anorexia nervosa: a systematic review of randomized controlled trials.

BACKGROUND: Anorexia nervosa (AN) is a serious psychiatric disease. Choice of acute inpatient care for AN is driven by the severity of symptoms and the level of risk to the patient. Inpatient hospitalization of patients with AN typically includes a behavioral weight gain protocol that is designed to address the core features of the disorder: weight, appetite, and distorted thoughts and behavior. Some add-on treatments may also be included in the inpatient treatment model and may have potential benefits, including faster or greater weight gain; such treatments include psychotherapy, psychoeducation, pharmacological treatment, and nutritional replacement. OBJECTIVE: The goal of this study was to systematically review randomized clinical trials (RCTs) that have compared the efficacy of different forms of add-on treatment delivered during admission to a 24-hour hospital and to summarize the existing data regarding weight gain associated with such pharmacological, medical, and psychological interventions. METHODS: Systematic electronic and manual searches were conducted to identify published RCTs concerning inpatient treatment of AN. Weight gain was used as the main outcome variable. RESULTS: Overall, no significant increase in weight recovery was reported with atypical antipsychotics compared to placebo or therapy as usual. Only one study showed slight benefits in young patients during hospitalization (d=0.77; 95% confidence interval [CI] -0.09-1.64). No significant effects on weight recovery were found for antidepressants (d=-0.10; 95% CI=-0.63-0.42). In addition, none of the add-on psychotherapy techniques that were evaluated demonstrated superiority compared with control interventions in the inpatient setting. Cyclic enteral nutrition was studied in one RCT in which it demonstrated superiority compared to oral refeeding only (d=0.97; 95% CI=0.51-1.47). Other less common treatments such as bright light therapy and lithium carbonate were not found to produce additional significant weight improvement compared with placebo. CONCLUSION: Most add-on treatments during the acute inpatient phase of AN treatment are not effective in increasing weight recovery. Long-term follow-up studies after the acute treatment phase are needed to make evidence-based recommendations.