Perspectives and preliminary experiences of psychedelics for the treatment of eating disorders: A systematic scoping review.

OBJECTIVE: Research regarding the therapeutic application of psychedelics and psychedelic-assisted psychotherapy in the treatment of eating disorders (EDs) has begun to emerge. This systematic scoping review aimed to map and synthesise the existing evidence regarding the participant reported efficacy and perspectives concerning psychedelics in the treatment of EDs, and to identify significant research gaps. METHOD: A systematic search was undertaken across several databases in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. RESULTS: 1290 publications were identified, 1135 after duplicates removed, with 17 meeting full-eligibility criteria. Overall, findings suggested that most participants reported experiencing a meaningful reduction in their ED symptoms and having positive experiences or an openness to explore psychedelics as a treatment for ED symptoms, although some noted concerns of adverse effects and the importance of having psychological support to increase safety and efficacy. CONCLUSIONS: While preliminary research suggests psychedelics and psychedelic-assisted psychotherapy may be a viable treatment option for ED symptoms, further research with more robust research designs is required to increase confidence in its efficacy, generalisability, and safety as a therapeutic medium.

Ayahuasca ceremony leaders' perspectives on special considerations for eating disorders.

Eating disorders (EDs) are difficult conditions to resolve, necessitating novel treatments. Ayahuasca, a psychedelic plant medicine originating in Indigenous Amazonian communities, is being investigated. Aspects of ceremonial ayahuasca use (purging, dietary restrictions) appear similar to ED behaviors, raising questions about ayahuasca's suitability as an intervention for individuals with EDs. This study explored the perspectives of ayahuasca ceremony leaders on these and other considerations for ceremonial ayahuasca drinking among individuals with EDs. A qualitative content analysis of interviews was undertaken with 15 ayahuasca ceremony leaders, the majority of whom were from the West/Global North. Screening for EDs, purging and dietary restrictions, potential risks and dangers, and complementarity with conventional ED treatment emerged as categories. The findings offer ideas, including careful screening and extra support, to promote safe and beneficial ceremony experiences for ceremony participants with EDs. More research is needed to clarify the impacts of ceremony-related purging and preparatory diets. To evolve conventional models of treatment, the ED field could consider Indigenous approaches to mental health whereby ayahuasca ceremony leaders and ED researchers and clinicians collaborate in a decolonizing, bidirectional bridging process between Western and Indigenous paradigms of healing.

"But the reality is it's happening": A qualitative study of eating disorder providers about psilocybin-assisted psychotherapy.

OBJECTIVE: This study invited providers who care for patients with eating disorders to inform engagement, communication, and collaboration with psilocybin-assisted psychotherapy interventions. METHOD: Medical and mental health providers who treat patients with eating disorders were recruited via professional referral networks and participant driven sampling from across California to participate in one of five focus groups. Discussion topics included prior knowledge of psychedelic therapy, interest/concerns related to psilocybin therapy, and opportunities for collaboration. Study team members completed iterative rounds of coding with a grounded theory approach. RESULTS: A total of 32 participants reported a range of familiarity with psychedelics. Some raised concerns about the risks of administering psilocybin to malnourished patients and to those with psychological comorbidities. Despite these concerns, participants were hopeful to see psilocybin therapy as a treatment for patients with eating disorders. In anticipating challenges, providers had concerns about equity in access to care among publicly insured and non-English speaking patients. They requested opportunities for continuing education about psilocybin therapy. DISCUSSION: Our findings demonstrate provider interest in psilocybin therapy for the treatment of patients with eating disorders. As psilocybin therapy interventions are developed, providers caring for patients with eating disorders value collaboration to improve longitudinal patient outcomes. PUBLIC SIGNIFICANCE: This study invited healthcare providers of patients with eating disorders to discuss their thoughts around the use of psilocybin-assisted psychotherapy in this population. Findings will help inform emerging psilocybin therapy clinical trials with the goal of successful translation and adoption in real world clinical settings.

Psychiatric visits during the postpartum year in women with eating disorders who continue or discontinue antidepressant treatment in pregnancy.

OBJECTIVE: To determine the association between continued antidepressant use in pregnancy and postpartum psychiatric visits for eating (ED) or mood/anxiety disorders in women with preexisting ED. METHOD: Using Danish health registry data (1998-2015), we identified 3529 pregnancies in women with ED prepregnancy: (i) 564 with continued antidepressant use before and during pregnancy; (ii) 778 with discontinued antidepressants before pregnancy; (iii) 2137 unexposed. Outpatient and inpatient postpartum visits for an ED or a mood/anxiety disorder constituted the outcome measures. We estimated hazard ratios (HRs) and 95% confidence intervals (CI) using Cox regression with inverse probability of treatment weighting, and performed stratified analyses by antidepressant prescription filling in the first 3 months postpartum. RESULTS: The weighted cumulative incidence for an ED visit at end of follow-up was 4.5% (continued) and 4.8% (discontinued). We found no association between continued antidepressant and postpartum ED visit, relative to discontinued (HR: 0.89, 95% CI: 0.52-1.52). The HR for postpartum mood/anxiety disorder visit was 1.27 (95% CI: 0.68-2.36) with continued antidepressants versus discontinued but decreased if more than two antidepressant prescriptions were refilled. Continued antidepressant use was associated with a 57% reduced likelihood of a postpartum ED visit versus discontinued use in pregnancies with antidepressant prescription refills in the early postpartum. CONCLUSION: Among women with preexisting ED, there was no association between continued antidepressant use during pregnancy and the likelihood of postpartum psychiatric visits, relative to discontinued antidepressants before pregnancy. Continuation of treatment into the early postpartum is associated with reduced likelihood of postpartum ED visit. PUBLIC SIGNIFICANCE: Based on data from the Danish registries, we identified 3529 pregnancies among women with preexisting eating disorders before pregnancy. Women with continued antidepressant treatment both before and during pregnancy did not have a lower probability of having postpartum psychiatric visits for an eating disorder or for mood/anxiety disorders (often coexisting with eating disorders), relative to those who discontinued antidepressants before pregnancy. Further continuation of antidepressant treatment into the early postpartum is associated with improved maternal postpartum outcomes. However, residual confounding by disease severity limits confidence in this conclusion.

Psychedelic-Assisted Therapy for People with Eating Disorders.

PURPOSE OF REVIEW: A growing body of research suggests psychedelic-assisted therapy (PAT) may be safe and effective for a variety of mental health conditions. Among these, eating disorders have been a recent target of interest. This review provides an up-to-date summary of the potential mechanisms and use of PAT in people diagnosed with eating disorders, with a focus on anorexia nervosa. RECENT FINDINGS: Classic psychedelics may have transdiagnostic efficacy through several mechanisms relevant to eating disorder pathology. Interest in, and efforts to increase access to PAT are both high. Early clinical trials are focused on establishing the safety and utility of this treatment in eating disorders, and efficacy remains unclear. High-quality published data to support the use of PAT for people with eating disorders remains lacking. Recent studies however suggest PAT has the potential to augment the efficacy of current interventions for these difficult-to-treat conditions.

Psychopharmacologic Management of Eating Disorders.

PURPOSE OF REVIEW: Identifying medications that may be used as therapeutic agents for eating disorders is a longstanding focus of research, with varying degrees of success. The present review consolidates the most recent findings on pharmacological treatment of three eating disorders, including anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). RECENT FINDINGS: Recent research suggests that olanzapine demonstrates positive effects on weight gain among outpatients with AN. There are fewer recent advances in psychopharmacological treatment for BN and BED, likely due to the relative success of prior medication trials. Olanzapine is the first medication to safely promote weight gain among individuals with AN. Fluoxetine is FDA-approved for BN treatment, and lisdexamfetamine is FDA-approved for BED treatment. BN and BED also generally respond well to SSRIs prescribed off-label. Research on psychopharmacological treatments for other eating disorders, such as avoidant-restrictive food intake disorder and other specified feeding and eating disorders, are sorely needed.

Evaluating the use of lamotrigine to reduce mood lability and impulsive behaviors in adults with chronic and severe eating disorders.

BACKGROUND: Gold-standard psychological and pharmacological treatments for bulimic-spectrum eating disorders only result in remission for around 50% of patients; patients with affective lability and impulsivity represent a subgroup with particularly poor outcomes. Both dialectical behavior therapy (DBT), a treatment for emotion dysregulation, and lamotrigine, a mood stabilizer, have demonstrated promise for targeting affective lability and impulsivity; however, data exploring the combination of these interventions remain limited. OBJECTIVE: We followed a group of women with recurrent dysregulated eating behaviors (N = 62) throughout intensive DBT treatment and compared the symptom trajectory of those prescribed lamotrigine (n = 28) and those who were not (n = 34). METHOD: Participants completed surveys every 2 weeks throughout treatment. RESULTS: Group analyses suggested that all participants self-reported decreases in emotional reactivity, negative urgency, and symptoms of borderline personality disorder (BPD). The lamotrigine group reported greater elevations in BPD symptoms at baseline, but demonstrated steeper decreases in emotion and behavioral dysregulation than the non-matched comparison group. Within-subject analyses suggested that within the lamotrigine group, subjects reported greater decreases in symptoms following prescription of lamotrigine. CONCLUSIONS: Findings provide initial data suggesting that lamotrigine could be useful as an adjunctive treatment for patients with affective lability and impulsivity. LEVEL OF EVIDENCE: IV, time series without randomization.

Candida guilliermondii-induced chorioretinitis in a patient with eating disorder.

Candidemia is a life-threatening fungal infection among patients undergoing long-term intravenous catheterization, hematopoietic stem cell transplantation, or immunosuppressive therapy, as well as patients with severe immunodeficiency or cancer. Endophthalmitis is a rare but severe form of ocular inflammation caused by infection of the intraocular cavity, which can lead to irreversible visual loss if not treated properly and promptly. The initial manifestation typically involves chorioretinitis, which requires early diagnosis and appropriate treatment. Candida guilliermondii is a non-Candida albicans yeast species; its frequency of detection in Japan has increased in recent years, and many drug-resistant and less-chorioretinitis-related strains are known. Here, we describe a 17-year-old girl with an eating disorder who exhibited chorioretinitis because of catheter-related bloodstream infection (CRBSI) caused by C. guilliermondii. The patient was hospitalized with severe weight loss, and she was presumed to develop candidemia because of immunosuppression during central parenteral nutrition therapy with a peripherally inserted central catheter. After onset of CRBSI, the catheter was immediately removed. Antifungal therapy was modified following fundus examination, fungal species confirmation, and drug sensitivity confirmation; thus, the patient recovered without long-term complications. To the best of our knowledge, this is the first report of C. guilliermondii-induced chorioretinitis in a patient with an eating disorder. Prolonged malnutrition and immunosuppression during nutritional therapy create a risk of candidemia in patients with eating disorders. After the onset of CRBSI, early administration and appropriate use of antifungal agents, with respect to specific ocular complications, are important for reduction of both mortality and ocular complications.

Perspectives on psychedelic treatment and research in eating disorders: a web-based questionnaire study of people with eating disorders.

Approximately 1.25 million people in the UK suffer from an eating disorder, yet the treatment options show limited efficacy, warranting the need for novel approaches. This study aimed to investigate the perspectives of people with eating disorders on the use of complementary therapies and psychedelic research and treatment. Two hundred participants with eating disorders took part in this web survey study. The majority of participants (70%) had used a complementary treatment to manage their eating disorder. Participants believed that psychedelic research was worthwhile in the context of a moderate level of concern. The most popular solutions to meet these concerns included providing education around psychedelics and their effects and use in psychiatry and experiencing endorsement from professionals in the area. Moreover, participant responses emphasized the need for a safe, monitored environment and the patient-therapist rapport in the context of psychedelic treatment. The findings are explored concerning future trials of psychedelics as a treatment for eating disorders.

The Role of the Noradrenergic System in Eating Disorders: A Systematic Review.

Noradrenaline (NE) is a catecholamine acting as both a neurotransmitter and a hormone, with relevant effects in modulating feeding behavior and satiety. Several studies have assessed the relationship between the noradrenergic system and Eating Disorders (EDs). This systematic review aims to report the existing literature on the role of the noradrenergic system in the development and treatment of EDs. A total of 35 studies were included. Preclinical studies demonstrated an involvement of the noradrenergic pathways in binge-like behaviors. Genetic studies on polymorphisms in genes coding for NE transporters and regulating enzymes have shown conflicting evidence. Clinical studies have reported non-unanimous evidence for the existence of absolute alterations in plasma NE values in patients with Anorexia Nervosa (AN) and Bulimia Nervosa (BN). Pharmacological studies have documented the efficacy of noradrenaline-modulating therapies in the treatment of BN and Binge Eating Disorder (BED). Insufficient evidence was found concerning the noradrenergic-mediated genetics of BED and BN, and psychopharmacological treatments targeting the noradrenergic system in AN. According to these data, further studies are required to expand the existing knowledge on the noradrenergic system as a potential target for treatments of EDs.

Role of Nociceptin/Orphanin FQ-NOP Receptor System in the Regulation of Stress-Related Disorders.

Nociceptin/orphanin FQ (N/OFQ) is a 17-residue neuropeptide that binds the nociceptin opioid-like receptor (NOP). N/OFQ exhibits nucleotidic and aminoacidics sequence homology with the precursors of other opioid neuropeptides but it does not activate either MOP, KOP or DOP receptors. Furthermore, opioid neuropeptides do not activate the NOP receptor. Generally, activation of N/OFQ system exerts anti-opioids effects, for instance toward opioid-induced reward and analgesia. The NOP receptor is widely expressed throughout the brain, whereas N/OFQ localization is confined to brain nuclei that are involved in stress response such as amygdala, BNST and hypothalamus. Decades of studies have delineated the biological role of this system demonstrating its involvement in significant physiological processes such as pain, learning and memory, anxiety, depression, feeding, drug and alcohol dependence. This review discusses the role of this peptidergic system in the modulation of stress and stress-associated psychiatric disorders in particular drug addiction, mood, anxiety and food-related associated-disorders. Emerging preclinical evidence suggests that both NOP agonists and antagonists may represent a effective therapeutic approaches for substances use disorder. Moreover, the current literature suggests that NOP antagonists can be useful to treat depression and feeding-related diseases, such as obesity and binge eating behavior, whereas the activation of NOP receptor by agonists could be a promising tool for anxiety.

Positive effects of psychedelics on depression and wellbeing scores in individuals reporting an eating disorder.

PURPOSE: Psychedelic therapy is showing promise for a broad range of mental health conditions, indicative of a transdiagnostic action. While the efficacy of symptom-focused treatments for eating disorders (EDs) is limited, improved mental health and psychological wellbeing are thought to contribute to greater treatment outcomes. This study provides the first quantitative exploration of the psychological effects of psychedelics in those reporting an ED diagnosis. METHODS: Prospective, online data were collected from individuals planning to take a psychedelic drug. Twenty-eight participants reporting a lifetime ED diagnosis completed measures of depressive symptomology (Quick Inventory of Depressive Symptomology; QIDS-SR16) and psychological wellbeing (Warwick-Edinburgh Mental Wellbeing Scale; WEMWBS) 1-2 weeks before, and 2 weeks after a psychedelic experience. Twenty-seven of these participants also completed a measure of emotional breakthrough [Emotional Breakthrough Inventory (EBI)] in relation to the acute psychedelic experience. RESULTS: Bayesian t tests demonstrated overwhelming evidence for improvements in depression and wellbeing scores following the psychedelic experience. Marginal evidence was also found for a correlation between emotional breakthrough and the relevant mental health improvements. CONCLUSION: These findings provide supportive evidence for positive psychological aftereffects of a psychedelic experience that are relevant to the treatment of EDs. It is hoped that this will encourage further research and will bolster initiatives to directly examine the safety and efficacy of psychedelic assisted therapy as a treatment of EDs in future clinical trials. LEVEL OF EVIDENCE: Level III, cohort study.

Eating Disorders and Psychofarmachology: Rethink the Treatment of Eating Disorders.

The pharmacological approach to eating disorders (ED) is effective in a few conditions, and to date, no treatment has shown certain efficacy in treating patients with this disorder. Furthermore, attempts to regulate hunger and satiety through modulation pharmacological effects of neurotransmitters and neuropeptides have shown only short-term benefit. However, in light of the serious impact of DCA on patients and the scarcity of non-pharmacological therapeutic approaches, research in this area should not be abandoned, also because new generation "molecules" become increasingly available. Many studies looked at efficacy of antipsychotics, Tryciclics, SSRI, mood stabilizers in the treatment of ED. Gabaergic circuit, the opioid one are extremely involved in the neurohormonal mechanisms of regulation of dietary behaviors and that molecules that influence these circuits could be used in the pharmacological treatment of ED as already happens in the case of Naltrexone, gabapentine or gabaergic drugs.

Psychotropic medication use in treatment-seeking youth with eating disorders.

OBJECTIVE: Psychotropic medication use in youth with eating disorders (EDs) is poorly understood despite high co-occurrence of psychiatric disorders. This study examined characteristics associated with medication use in treatment-seeking youth with EDs. METHOD: Youth up to age 18 reported on medication use when presenting to an academic medical center outpatient ED service in the United States. Data presented were collected between 1998-2015. RESULTS: The sample (N = 604) was predominantly female (90.6%) with a mean age of 15.3 years (SD = 2.3). Approximately one-third (30%, n = 173) were taking psychotropic medications (40%, n = 70, were taking multiple medications). Antidepressant use was most common (26%, n = 152), followed by atypical antipsychotics (8%, n = 43). Adjusting for co-occurring psychiatric disorders, non-Hispanic Whites who had received prior treatment (psychotherapy, hospitalization) were significantly more likely to be using medication. Longer illness duration and prior treatment were associated with greater antidepressant use. For atypical antipsychotics, prior hospitalization was associated with greater use. CONCLUSIONS: Findings confirm moderate psychotropic medication use among young patients with EDs despite a lack of clarity regarding optimally effective pharmacologic interventions in this population. Pharmacological trials examining the efficacy of medications for young patients with EDs are warranted to inform future prescribing practice.

Orthorexia nervosa and comorbid depression successfully treated with mirtazapine: a case report.

Orthorexia nervosa (ON) is a recently proposed eating disordered behaviour characterized by an obsessional or exaggerated fixation on healthy eating. The published literature is scarce regarding its classification, clinical presentation, management and long-term outcomes. Herein, we present the clinical and follow-up findings of an 18-year-old woman with ON comorbid with depression, successfully treated with mirtazapine. The patient had a 12-month history of obsessional behaviours for "healthy food", characterized by suppression of sugar and fat from her diet, tightly counted meal calorie content, eating only self-made meals, avoidance of eating in public, unacceptance of other person's opinions on diet, social isolation and a weight loss of 15 kg (body mass index of 16.2 kg/m2). A score of 19-points was initially obtained on the ORTO-15 questionnaire, suggesting the presence of orthorexic tendencies and behaviours. The patient also reported a 1-month history of depressed mood, anxiety, anhedonia, fatigue, insomnia with early morning waking, leading to the presumptive diagnosis of ON with comorbid depression. Treatment with mirtazapine for 11 months resulted in the remission of the disordered eating behaviour, a sustained regain of weight, a score of 41-points on the ORTO-15, and to the resolution of depressive symptomatology (including insomnia). To our knowledge, this is the first description of ON with comorbid depression successfully treated with mirtazapine. This case highlights the possible usefulness of mirtazapine as a treatment option for patients with ON. However, randomized controlled studies are warranted to confirm the current findings.

Treating Individuals With Eating Disorders: Part 2.

Health care providers often need additional training to understand the recommended treatment for eating disorders (EDs). Treatment varies by diagnosis and particularly for vulnerable populations (e.g., adolescents, pregnant women). EDs have life-threatening consequences and require timely interventions. Treatment tends to focus on decreasing disordered eating behaviors, psychological suffering, and nutritional deficits associated with EDs while simultaneously promoting whole health. An overview of EDs was presented in the first article of this two-part series about treating EDs. The current article discusses pharmacological and nonpharmacological evidence-based treatments for EDs. [Journal of Psychosocial Nursing and Mental Health Services, 58(4), 9-15.].

Beneficial effects of leptin substitution on impaired eating behavior in lipodystrophy are sustained beyond 150 weeks of treatment.

AIM: Metreleptin treatment in lipodystrophy patients improves eating behavior with increased satiety and reduced hunger. However, no data are available whether effects are maintained beyond 52 weeks of treatment. METHODS: A prospective study with measurements at baseline and at >150 weeks of metreleptin treatment was performed. Five female lipodystrophy patients with indication for metreleptin were included. Behavioral aspects of hunger- and satiety regulation were assessed by validated eating behavior questionnaires and visual analog scales assessing hunger and satiety feelings before and after a standardized meal. RESULTS: Hunger rated on visual analog scales at 120 min after the meal significantly decreased from 46 ±â€¯10 mm at baseline to 17 ±â€¯6 mm at long-term assessment. Furthermore, satiety at 5 and 120 min after the meal significantly increased from baseline to long-term assessment (5 min: 70 ±â€¯7 mm to 87 ±â€¯3 mm; 120 min: 43 ±â€¯10 mm to 79 ±â€¯8 mm). On the Three Factor Eating Questionnaire, the mean value of factor 3 (hunger) significantly decreased from 9.2 ±â€¯0.2 at baseline to 2.6 ±â€¯1.5 at long-term assessment. In the Inventory of Eating Behavior and Weight Problems Questionnaire, mean values for scale 2 (strength and triggering of desire to eat) and scale 7 (cognitive restraint of eating) significantly decreased from baseline (31.6 ±â€¯4.8 and 11.4 ±â€¯2.2, respectively) to long-term assessment (14.0 ±â€¯2.1 and 10.0 ±â€¯1.9). CONCLUSION: First evidence is presented that long-term metreleptin treatment of >150 weeks has sustained effects on eating behavior with increased satiety, as well as reduced hunger and hunger-related measures.

Management of ARFID (Avoidant Restrictive Food Intake Disorder) in a 12-year-old on a Paediatric Ward in a General Hospital: Use of Mirtazapine, Partial Hospitalisation Model and Family Based Therapy.

BACKGROUND: Avoidant Restrictive Food Intake Disorder (ARFID), at the cross roads of eating and feeding disorders, is sometimes called an "umbrella diagnosis" as it covers a certainly large and rather heterogeneous list of eating symptoms. It came with the DSM5 (2013) but still, there are no clear guidelines re diagnosis and treatment. PURPOSE: Through this case, we aim to report not only a presentation of ARFID, but also how this relatively new and emerging diagnostic category has been identified and managed on a Pediatric Ward, in a General Hospital. SUBJECTS AND METHODS: This study reports the case of a 12y old girl Irish girl with ARFID treated by a multi-disciplinary team on a Pediatric Ward in a general hospital. A literature review regarding ARFID was concomitantly carried on, in order to consider the current therapeutic options recommended. RESULTS: 3 admissions on a pediatric Ward were necessary for this patient with ARFID, who was successfully managed with a partial hospitalization model, Family Based Treatment (FBT) and Mirtazapine. CONCLUSIONS: The dynamic around the management of this condition is the occasion to discuss the other therapeutic options suggested these days, and more specifically the different pharmacological molecules that have also been used in young patients with ARFID and the importance of involving a multi-disciplinary team.

A systematic review of cost-effectiveness studies of prevention and treatment for eating disorders.

BACKGROUND: Eating disorders are serious mental disorders and are associated with substantial economic and social burden. The aim of this study is to undertake a systematic review of the cost-effectiveness studies of both preventive and treatment interventions for eating disorder. METHOD: Electronic databases (including the Cochrane Controlled Trial Register, MEDLINE, PsycINFO, Academic Search Complete, Global Health, CINAHL complete, Health Business Elite, Econlit, Health Policy Reference Center and ERIC) were searched for published cost-effectiveness studies of eating disorder prevention and treatment including papers published up to January 2017. The quality of studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: In all, 13 studies met the review inclusion criteria as full cost-effectiveness studies and 8 were published since 2011. The studies included three modelled and one trial-based study focused on prevention, two trial-based and one modelled study for anorexia nervosa treatment and three trial-based studies for bulimia nervosa treatment. The remaining studies targeted binge-eating disorder or non-specific eating disorder treatment. The average percent of CHEERS checklist items reported was 71% (standard deviation 21%). Eating disorder interventions were mainly cost-saving or more effective and more costly compared to comparators; however, some results did not reach statistical significance. In the two studies that achieved 100% CHEERS checklist, one study reported that a cognitive dissonance intervention might be cost-effective for prevention of anorexia nervosa and bulimia nervosa with a 90% participation rate and the second study supported lisdexamfetamine to be cost-effective in the treatment of binge-eating disorder. Insufficient evidence for long-term cost-effectiveness (e.g. over 2 years) was found. CONCLUSION: Cost-effectiveness studies in eating disorder appear to be increasing in number over the last 6 years. Findings were inconsistent and no firm conclusion can be drawn with regard to comparative value-for-money conclusions. However, some promising interventions were identified. Further research with improved methodology is required.

Impact of brown rice-specific γ-oryzanol on epigenetic modulation of dopamine D2 receptors in brain striatum in high-fat-diet-induced obesity in mice.

AIMS/HYPOTHESIS: Overeating of dietary fats causes obesity in humans and rodents. Recent studies in humans and rodents have demonstrated that addiction to fats shares a common mechanism with addiction to alcohol, nicotine and narcotics in terms of a dysfunction of brain reward systems. It has been highlighted that a high-fat diet (HFD) attenuates dopamine D2 receptor (D2R) signalling in the striatum, a pivotal regulator of the brain reward system, resulting in hedonic overeating. We previously reported that the brown rice-specific bioactive constituent γ-oryzanol attenuated the preference for an HFD via hypothalamic control. We therefore explored the possibility that γ-oryzanol would modulate functioning of the brain reward system in mice. METHODS: Male C57BL/6J mice fed an HFD were orally treated with γ-oryzanol, and striatal levels of molecules involved in D2R signalling were evaluated. The impact of γ-oryzanol on DNA methylation of the D2R promoter and subsequent changes in preferences for dietary fat was examined. In addition, the effects of 5-aza-2'-deoxycytidine, a potent inhibitor of DNA methyltransferases (DNMTs), on food preference, D2R signalling and the levels of DNMTs in the striatum were investigated. The inhibitory effects of γ-oryzanol on the activity of DNMTs were enzymatically evaluated in vitro. RESULTS: In striatum from mice fed an HFD, the production of D2Rs was decreased via an increase in DNA methylation of the promoter region of the D2R. Oral administration of γ-oryzanol decreased the expression and activity of DNMTs, thereby restoring the level of D2Rs in the striatum. Pharmacological inhibition of DNMTs by 5-aza-2'-deoxycytidine also ameliorated the preference for dietary fat. Consistent with these findings, enzymatic in vitro assays demonstrated that γ-oryzanol inhibited the activity of DNMTs. CONCLUSIONS/INTERPRETATION: We demonstrated that γ-oryzanol ameliorates HFD-induced DNA hypermethylation of the promoter region of D2R in the striatum of mice. Our experimental paradigm highlights γ-oryzanol as a promising antiobesity substance with the distinct property of being a novel epigenetic modulator.