Approved and Pipeline Pharmacological Interventions for Eating Disorders (2010–2025): 15 Years of Progress (or Lack Thereof)

Abstract

Eating disorders (EDs) are complex psychiatric conditions characterized by disruptions in eating behaviors, body image concerns, and profound medical and psychosocial consequences. Despite their significant global prevalence, coupled with high morbidity and mortality rates, pharmacological treatment options remain limited. This review synthesizes evidence from clinical drug trials conducted between 1 January 2010 and 1 January 2025, supplemented with relevant literature, to evaluate the current and emerging pharmacological landscape for EDs. A systematic search of the U.S. Clinical Trials Registry (ClinicalTrials.gov) identified 43 eligible phase I–IV clinical trials for the treatment of anorexia nervosa (n = 12), binge eating disorder (n = 27), bulimia nervosa (n = 2), and rumination disorder (n = 2). Among 24 distinct compounds studied, only 1 agent, lisdexamfetamine dimesylate, received approval from the U.S. Food and Drug Administration (FDA) for an ED during this period. Notably, few agents have demonstrated positive results in late-stage trials and remain in development for EDs as of 2025. While some emerging agents show promise, such as solriamfetol and psilocybin, there remains a significant lack of evidence-based pharmacological interventions for anorexia nervosa and a dearth of progress in pharmacotherapy for bulimia nervosa. Overall, the past 15 years have witnessed limited advancements in pharmacotherapy for EDs. There remains an urgent need for rigorous clinical trials in this area in addition to increased prioritization of ED research at the public health level to overcome longstanding barriers in the treatment of EDs.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40263-025-01248-7.

Key Points

Despite the increasing global prevalence of eating disorders, progress in pharmacological treatment has been slow, with only two medications approved by the U.S. Food and Drug Administration: fluoxetine for bulimia nervosa in 1994 and lisdexamfetamine for binge eating disorder in 2015.

Emerging treatments, including solriamfetol and psilocybin, show potential, however, there remains a critical gap in evidence-based pharmacotherapy for eating disorders, and few drugs remain in late-stage clinical trials as of 2025.

Introduction

Eating disorders (EDs) are chronic conditions characterized by significant disturbances in eating behaviors and related attitudes toward weight, body shape, appearance, and health [1]. Often emerging in adolescence or early adulthood, these disorders frequently persist for years, affecting individuals across diverse demographics and cultural contexts [2]. EDs are increasingly recognized as a significant public health concern due to their widespread prevalence, associated disability, and substantial mortality [3].

The DSM-5 categorizes EDs into the following categories: anorexia nervosa (AN), bulimia nervosa (BN), binge-eating disorder (BED), avoidant/restrictive food intake disorder (ARFID), pica, rumination disorder, other specified feeding or eating disorder (OSFED), and unspecified feeding and eating disorders [1]. The diagnosis and categorization of EDs are challenging due to poor screening practices, the dynamic nature of eating disorder diagnoses, limited training on eating disorders among healthcare professionals, and low rates of help-seeking behavior among individuals affected by EDs [4–8]. Moreover, the presence of EDs that are not formally recognized, such as orthorexia, characterized by an obsessive focus on “healthy” eating, and muscle dysmorphia, marked by a preoccupation with insufficient muscle mass, further complicates both diagnosis and treatment [9, 10].

Globally, the lifetime prevalence of EDs is estimated at 8.4% among women and 2.2% among men, and analysis shows an increasing prevalence rate over time [11]. AN affects up to 4% of women and 0.3% of men over a lifetime, while BN is observed in up to 3% of women and more than 1% of men [12]. BED also affects a significant portion of the population and is estimated to impact 1.5% of women and 0.3% of men worldwide [13]. OSFED has the highest lifetime prevalence at 7.4% [11]. In addition to disrupting individuals’ eating patterns, EDs carry severe medical and psychological repercussions.

Mortality rates associated with EDs are alarmingly high. AN is consistently estimated to carry a mortality rate more than five times higher than that of the general population, the highest of any psychiatric illness [14–16]. Moreover, mortality rates for BN, while lower than those for AN, are nonetheless around twice that of the general population [14, 15]. More than 3.3 million healthy life years worldwide are lost due to EDs [17], and 1.3 million disability adjusted life years in 2018–2019 in just the USA alone [18], attributed to premature mortality and reduction in quality of life. Individuals with AN, BN, and BED experience significantly lower health-related quality of life compared with the general population [19, 20]. In addition to their high mortality, individuals with AN and BN experience numerous serious medical complications. AN is associated with a variety of life-threatening issues, including osteoporosis, bone marrow suppression, and cardiac arrhythmias, all of which contribute to its high morbidity [21]. Similarly, BN can lead to severe complications, such as electrolyte imbalances, seizures, renal failure, and tooth erosion, which may require intensive medical intervention [21]. In the USA, the economic burden of eating disorders is substantial, with total costs estimated at $64.7 billion annually (95% CI $63.5–66.0 billion) for 2018–2019, which translates to more than $11,000 per affected individual, in addition to $326.5 billion attributable to reductions in well-being associated with EDs [22].

This substantial public health burden is compounded by high rates of resistance to treatment among individuals with EDs. Data from the National Quality Registry for Eating Disorders Treatment in Sweden indicated that remission rates for eating disorders decreased from 21% in 2014 to 14% in 2016, with more than half of the patients lost to follow-up [23]. Following an adequate course of treatment with current evidence-based therapies, nearly half of patients with AN will not recover, and it is known that longer illness duration is a predictor of poorer outcomes [24, 25]. A 2014 study found that between 23.0% and 34.5% of patients remained unchanged after specialized inpatient treatment for AN [26]. In bulimia nervosa (BN), the situation is similarly concerning. A meta-analysis of 45 randomized controlled trials (RCTs) reported that only 35.4% of treatment completers achieved symptom abstinence post-treatment, and this figure dropped to 29.9% when considering all randomized patients [27]. Thus, more than 60% of patients may fail to abstain from core BN symptoms even after receiving current treatments. Likewise, following psychological or behavioral treatments for binge eating disorder, a meta-analysis of 39 RCTs found that nearly 50% of patients did not fully respond to treatment [28].

Current standard practices for the treatment of EDs usually comprise a combination of pharmacotherapy and psychotherapy in a variety of practice settings, though limited efficacy is found with these treatments [23–29]. Although a variety of medications are used “off-label” in the treatment of eating disorders and their psychiatric comorbidities, the U.S. Food and Drug Administration (FDA) has only approved two medications for eating disorders. In 1994, the FDA approved fluoxetine for BN, and in 2015, lisdexamfetamine was approved for BED, with no current FDA-approved medication for the treatment of AN [30]. Current evidence-based psychotherapy in adults includes cognitive behavioral therapy (CBT), dialectical behavioral therapy (DBT), interpersonal psychotherapy (IPT), Maudsley model of anorexia nervosa treatment for adults (MANTRA), and specialist supportive clinical management (SSCM) [31, 32]. In adolescence, the only well-established evidence-based treatments (level 1 evidence) include family-based treatment for AN and family-based treatment for BN, with no evidence for BED and ARFID [33].

While considerable efforts have been made to catalog progress in psychotherapeutic and behavioral interventions for EDs [34–37], to our knowledge, comparatively less attention has been given to advancements in pharmacological interventions. This review synthesizes data on medications investigated in clinical trials from 2010 through the beginning of 2025, focusing on eating disorders. It details medication classes, mechanisms of action, indications, evidence for efficacy, and reported adverse effects.

Search Methods

This review was conducted as a narrative synthesis on the basis of a systematic search of clinical drug trials in eating disorders, supplemented by relevant literature. ClinicalTrials.gov was searched for phase I–IV trials conducted between 1 January 2010 and 1 January 2025. The search was restricted to interventional studies evaluating pharmacological agents in AN, BN, BED, ARFID, OSFED, pica, and rumination disorder. Trials of pharmacological agents in phase I–IV were included if they evaluated psychiatric, behavioral, or weight-related outcomes in an eating disorder population. Studies limited to nondrug interventions, nutritional supplements, obesity without comorbid eating disorder, or trials that were withdrawn, suspended, or terminated were excluded. To provide additional context on mechanisms of action, drug classes, indications, and safety profiles, supplementary searches were performed in PubMed for publications linked to identified trials and for background literature on emerging agents. Data from eligible trials were extracted manually, with information summarized descriptively and organized by disorder. A flow chart alongside the detailed search strategy is provided as supplemental material.

Advances in Pharmacological Treatment of Anorexia Nervosa

A total of 12 clinical trials were identified investigating the effects of eight novel and repurposed agents on AN symptoms or complications from 2010 through the beginning of 2025. These compounds included two monoaminergic agents, two N-methyl-d-aspartate (NMDA) receptor modulators, one cholinergic agent, and three endocrine agents. Table 1 summarizes the clinical trials for anorexia nervosa from 1 January 2010 to 1 January 2025, sorted by class. A summary of each agent tested is presented in Supplementary Table 1, including mechanisms of action, dosing information, clinical trial phase, and notes to clinicians (involving effects on sedation, weight/lipids, dependence risk, and other information).

Table 1.

Summary of clinical trials for anorexia nervosa (2010–2025)

NCT registry number	Active drug (dose)	Control groups	Trial phase, design	N	Start year	End year	Sponsor	Primary outcomes	Main findings
Monoaminergic agents
NCT01170117 [38]	Olanzapine 2.5–10 mg daily	Placebo	Double-blind parallel group RCT (trial phase not indicated)	152	2010	2017 (actual)	New York State Psychiatric Institute	Rate of weight change, YBOCS	In patients with AN, olanzapine produced a greater increase in BMI over time, relative to placebo (0.259 [SD 0.051] versus 0.095 [SD 0.053] per month). Change in YBOCS obsessions subscale score over time did not significantly differ between groups (− 0.325 versus − 0.017 points per month)
NCT04661514 [39]	Psilocybin 25 mg in one session	N/A (open-label)	Phase 1 open-label single group trial	16	2021	2022 (actual)	University of California, San Diego	Adverse events (baseline to day 28), ECG parameters (baseline to D1, D7, D28), laboratory tests (baseline to D1, D7, D28), vital signs (baseline to D1, D7, D28), C-SSRS (baseline to D28)	Psilocybin therapy was found to be safe and well tolerated in female participants with anorexia nervosa, with no clinically significant changes in ECG, vital signs, suicidality, or other laboratory values. Adverse events were mild, transient, and participants generally found the treatment acceptable
NCT04505189	Psilocybin (up to) 25 mg in three sessions	N/A (open-label)	Phase 2, open-label single-group trial	21	2021	2024 (actual)	Imperial College London	RMQ, EDE, EDEQ - baseline to primary endpoint (6 weeks)	Pending (trial is completed)
NCT05481736	Psilocybin 25 mg	Active comparator: 1 mg psilocybin	Phase 2 double-blind parallel group RCT	32	2022	2024 (actual)	COMPASS Pathways	Change from baseline in EDEQ global score, week 4	Pending (trial is completed)
NCT04052568	Psilocybin 20–30 mg in up to four sessions	N/A (open label)	Phase 1 open-label single group trial	22	2019	2023 (actual)	Johns Hopkins University	Change in HADS score, 1 week post-final psilocybin session; change in EDQLS score, 2 months post-final psilocybin session	Pending (trial is completed)
NCT06399263	Psilocybin 20–30 mg in two sessions	N/A (open label)	Phase 2, open-label single-group trial	40	2024	2029 (estimated)	Marissa Raymond-Flesch, MD, MPH	BMI in adult women with AN, difference in BMI from D0 to D90	Pending (trial is active)
NMDA receptor modulators
NCT01996644 [40]	d-Cycloserine 250 mg/session	Placebo	Double-blind parallel group RCT (trial phase not indicated)	36	2013	2014	Washington University School of Medicine	Anxiety (as measured by the SUDS), difference in BMI	In patients with AN, exposure therapy for food anxiety with d-cycloserine produced a significantly greater increase in BMI relative to placebo. No statistically significant difference in anxiety was reported between groups
NCT04714541 [41]	Ketamine 0.75–1.2 mg/kg IV	N/A (open-label)	Phase 1 open-label single group trial	5	2021	2022 (actual)	Homeostasis Therapeutics, LLC	Changes in EDEQ, EDREQ, CIA for eating disorders scale, and behavior, mood; change from baseline through 12 months	Patients on a ketogenic diet treated with ketamine exhibited clinically significant improvements on the CIA, EDEQ Global score, EDEQ-Eating Concerns, EDEQ-Shape Concerns, EDEQ-Weight Concerns, EDREQ, Acceptance of Self and Body, and EDREQ-Social and Emotional Connection
Cholinergic agents
NCT06687993	Donepezil 2.5–5 mg/day	Placebo	Phase 2, double-blind parallel group RCT	147	2024	2030 (estimated)	Centre Hospitalier St Anne	Difference in BMI between inclusion (D0) and end of treatment (D90)	Pending (trial is active)
Endocrine agents
NCT06305182	Metreleptin 0.4–1.2 mL/day	Placebo	Phase 2, double-blind parallel group RCT	50	2024	2026 (estimated)	Gabriella Milos	Clinician-rated depression (HAMD-17) and body weight status (kg) between baseline (D−1), post-treatment (D14), and 5-week follow-up (D49)	Pending (trial is active)
NCT01642550 [42]	Relamorelin 100 mcg daily	Placebo	Phase 2, double-blind parallel group RCT	20	2012	2015 (actual)	Motus Therapeutics, Inc.	Change from baseline in body weight, baseline to D28	In women with AN, relamorelin led to a trend in weight gain after 4 weeks and significantly reduced gastric emptying time
NCT01121211 [43]	Testosterone 300 mcg	Placebo	Phase 2 double-blind parallel group RCT	90	2010	2016 (actual)	Massachusetts General Hospital	Change from baseline in weight (kg), baseline, 24 weeks; change from baseline in depression symptom severity (HAM-D, 0-23), baseline, 24 weeks	In women with AN, 24 weeks of low-dose testosterone therapy was associated with less weight gain and did not lead to sustained improvements in disordered eating symptoms, depression, or anxiety compared with placebo

Each identified agent investigated in the treatment of anorexia nervosa is described in detail in the main text, sorted by class

AN anorexia nervosa, BMI body mass index, C-SSRS Columbia-Suicide Severity Rating Scale, CIA Clinical Impairment Assessment, D day, ECG electrocardiogram, EDEQ Eating Disorder Examination Questionnaire, EDQLS Eating Disorder Quality of Life Scale, EDREQ Eating Disorder Recovery Endorsement Questionnaire, HADS Hospital Anxiety and Depression Scale, HAMD-17/HAM-D Hamilton Depression Rating Scale, IV intravenous, NCT National Clinical Trial (identifier number), RCT randomized controlled trial, RMQ Readiness and Motivation questionnaire, SD standard deviation, SUDS Subjective Units of Distress Scale, YBOCS Yale–Brown Obsessive Compulsive Scale

Monoaminergic Agents in Anorexia Nervosa

Two agents with primarily monoaminergic mechanisms of action were investigated for the treatment of AN, including olanzapine and psilocybin. Olanzapine (Zyprexa^®) is an atypical antipsychotic agent approved by the FDA for the treatment of schizophrenia and bipolar I disorder, which functions as a dopamine D2 and serotonin 5-HT2A receptor antagonist [44]. Its proposed mechanism in AN may involve modulation of dopamine and serotonin signaling, attenuation of hyperactive reward pathways, and promotion of weight gain and behavioral normalization [38, 45]. In a double-blind, placebo-controlled RCT for the treatment of AN, olanzapine produced a significantly greater increase in body mass index (BMI) over time than placebo (0.259 [standard deviation (SD) 0.051] versus 0.095 [SD 0.053] per month) [38]. However, there were no significant differences between groups in terms of psychological symptoms, as measured by change in the Yale–Brown Obsessive Compulsive Scale (YBOCS) obsessions subscale score over time (− 0.325 versus − 0.017 points per month) [38]. Overall, there is limited evidence for the use of atypical antipsychotics in AN [45], and findings regarding their effects on psychiatric symptoms in AN remain inconsistent [38, 46, 47]. Olanzapine is associated with notable adverse effects, including extrapyramidal symptoms, such as akathisia and tardive dyskinesia, in addition to QT prolongation, xerostomia, sedation, and increase in appetite [48]. As such, the use of olanzapine and other atypical antipsychotics in AN should be considered on a case-by-case basis [45].

Psilocybin is an orally administered psychedelic, which functions as a prodrug of psilocin and is thought to produce its psychotropic effects via biased agonism at the serotonin 5-HT2A receptor [49, 50]. Psilocybin has been investigated with positive results in the treatment of major depressive disorder, anxiety disorders, and substance use disorders [51]. It has been hypothesized that psilocybin may help in AN by modulating interoception and cognitive flexibility [52]. It entered phase 2 RCTs for the treatment of AN in 2021, and to date, five trials for this indication have been identified, during which 20–30 mg of psilocybin is administered orally in one or more sessions.

Preliminary data from a phase 1 open-label feasibility study assessed the safety, tolerability, and feasibility of psilocybin therapy in ten adult female participants with AN [39]. Psilocybin was found to be generally safe and well tolerated, with no clinically significant changes in electrocardiogram, vital signs, or suicidality, though two participants experienced transient, asymptomatic hypoglycemia that resolved within 24 h [39]. No trial results from RCTs investigating the efficacy of psilocybin in AN were identified. Of note, psilocybin remains classified as a Schedule I controlled substance, though it is not typically associated with a significant risk of dependence [53]. Reported adverse effects include headache, nausea, anxiety, dizziness, and elevated blood pressure [54].

NMDA Receptor Modulators in Anorexia Nervosa

During this period, two N-methyl-d-aspartate (NMDA) receptor modulators, including d-cycloserine and ketamine, were explored in the treatment of AN, comprising two clinical trials. As a partial agonist at the NMDA receptor, d-cycloserine has been investigated in the treatment of various psychiatric conditions, including anxiety disorders and obsessive compulsive disorder (OCD) [55]. In AN, its proposed mechanism involves the facilitation of fear extinction and enhancement of emotional learning during exposure therapy sessions [56]. d-Cycloserine entered a placebo-controlled clinical trial in 2013 for the treatment of food anxiety in AN [40]. Across four sessions, augmentation of exposure-based therapy with 250 mg d-cycloserine was associated with a significantly greater increase in body mass index compared with placebo; however, no statistically significant differences were observed in reported anxiety between groups [40]. Reported adverse effects include drowsiness, headache, fatigue, rash, and fever, though typically occurring only at higher doses [57].

Ketamine, on the contrary, is an antagonist at the NMDA receptor and possesses rapid-acting antidepressant properties. It is FDA approved for anesthesia and treatment-resistant depression (TRD) in its (S) enantiomer form, esketamine. Ketamine’s mechanism of action involves increasing glutamate release, which enhances synaptic plasticity, neurogenesis, and synaptogenesis [41, 58]. In AN, ketamine has been investigated in a phase 1 pilot study evaluating the combination of a therapeutic ketogenic diet and ketamine infusion [41]. Participants received intravenous ketamine at doses ranging from 0.75 to 1.2 mg/kg administered over 45 min. The study demonstrated significant improvements in clinical measures of impairment, eating disorder symptoms, and psychological recovery, with no major adverse effects reported. It should be noted that ketamine is a Schedule III controlled substance with documented abuse potential [59]. Adverse effects associated with ketamine include dissociative symptoms, transient elevations in blood pressure and heart rate, nausea, and dizziness [60].

Cholinergic Agents in Anorexia Nervosa

A single cholinergic agent, donepezil (Aricept^®), was investigated in AN during the review period, comprising one early stage clinical trial. Donepezil is an orally administered acetylcholinesterase inhibitor that is FDA approved for the management of Alzheimer’s disease [61]. Increasing evidence suggests that the cholinergic system is compromised in AN, promoting vulnerability to maladaptive eating and habit formation, thus, donepezil represents a promising area of therapeutic investigation [62, 63]. In November 2024, donepezil entered a multicenter, placebo-controlled phase 2 RCT to investigate its efficacy in the treatment of AN. No completed trials were identified investigating donepezil in AN, however, the current study (n = 147) has an estimated completion in early 2030. Commonly reported adverse effects include nausea, diarrhea, vomiting, insomnia, and fatigue [61].

Metabolic and Endocrine Agents in Anorexia Nervosa

A total of three unique endocrine agents were investigated in AN during this period, including metreleptin, relamorelin, and testosterone. These compounds are believed to act on pathways involved in appetite regulation, energy balance, and metabolic function [64, 65].

Metreleptin, a synthetic analog of leptin, is approved as adjunctive to diet to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy [66]. Known as the obese protein, leptin is an endogenous peptide hormone that acts as the body’s satiety signal [64]. It was hypothesized that treatment with metreleptin would normalize low circulating leptin levels in patients with AN [67]. Metreleptin entered a placebo-controlled phase 2 RCT for the treatment of AN in 2024 (n = 50), with an estimated completion in early 2026.

The quality of evidence regarding the use of metreleptin in AN is currently limited and primarily based on case reports and small, uncontrolled studies. Several case reports have documented rapid improvements in cognitive, emotional, and behavioral symptoms in patients with AN treated off label with metreleptin. For instance, Milos et al. reported beneficial effects on hyperactivity, repetitive thoughts of food, inner restlessness, and weight phobia in two out of three patients treated with metreleptin for up to 14 days [67]. Similarly, Antel et al. described substantial improvements in mood, eating disorder-related cognitions, and hyperactivity in a male adolescent with severe AN during a 24-day treatment period [68]. Commonly reported adverse effects associated with metreleptin include headache, hypoglycemia, weight loss, and abdominal pain [69].

Relamorelin is a subcutaneously administered ghrelin/growth hormone secretagogue receptor agonist under development for the treatment of AN, in addition to diabetic gastroparesis and chronic idiopathic constipation [42, 70]. In a double-blind, placebo-controlled trial, 22 women with anorexia nervosa were randomized to receive either relamorelin 100 μg subcutaneously daily or placebo for 4 weeks. The primary outcomes measured were changes in weight and gastric emptying time. The study found a trend toward weight gain in the relamorelin group (mean ± standard error of the mean [SEM] change: 0.86 ± 0.40 kg) compared with the placebo group (0.04 ± 0.28 kg; P = 0.07) [42]. Additionally, gastric emptying time was significantly shorter in the relamorelin group (median [interquartile range]: 58.0 [51.0, 78.0] min) compared with the placebo group (85.0 [75.8, 100.5] min; P = 0.03). [42]. Commonly reported adverse effects include headache, dizziness, bloating, nausea, and abdominal pain [70].

Testosterone is an androgen hormone primarily responsible for the development of male secondary sexual characteristics and is FDA approved for the treatment of male hypogonadism and delayed puberty in males [65]. Testosterone exerts its effects by binding to androgen receptors, influencing gene expression and protein synthesis, which in turn improves muscle mass, bone density, and erythropoiesis [65]. Testosterone is a Schedule III controlled substance with a potential for abuse, which may lead to anabolic steroid use disorder [71].

In AN, testosterone has been evaluated in a phase 2, double-blind, placebo-controlled trial of 90 women, in which participants received a low-dose transdermal patch delivering 300 mcg daily for 24 weeks [43]. Testosterone therapy was associated with less weight gain relative to placebo, and no significant difference in eating disorder symptoms, depression, or anxiety was noted between groups [43]. Reported adverse effects of testosterone in AN include acne, hirsutism, headaches, weight changes, changes in lipid profile and metabolism [72].

Challenges, Clinical Implications, and Future Directions

Research on pharmacological interventions in AN continues to present formidable challenges. Despite the presence of 12 trials examining pharmacological interventions for AN, no eligible late-stage trials for AN during this period were identified. This is in stark contrast to the number of drugs in late-stage clinical trials or approved for other psychiatric disorder classifications during similar periods [73–76]. For example, between 2009 and early 2025, 15 medications were approved by the FDA for depressive disorders, and 18 were investigated in phase 3 clinical trials [77].

Despite its high prevalence, morbidity, mortality, and significant public health burden, there are currently no effective medications and few effective nonpharmacological treatments for AN [29, 32]. The American Psychiatric Association (APA)’s current practice guidelines for AN do not include pharmacotherapy as an option [32]. Instead, they recommend ED-focused psychotherapy and family based treatment (i.e., caregiver education) alongside individualized weekly goals for weight gain and target weight. Likewise, while most international guidelines recommend individual and family based psychotherapy, few contain recommendations for or against the use of specific medications in AN [78]. However, there is no reliable evidence demonstrating the superiority of specific psychological interventions (including cognitive behavioral and family based therapy) over treatment as usual [34, 35]. As it does not appear that any pharmacological agents will advance out of the pipeline in the near future, there is a strong need for novel agents and interventions to treat AN, supported by well-powered, placebo-controlled clinical trials.

Alongside the pharmacological interventions under examination for use in AN, emerging interest has been directed toward neuromodulation techniques and novel therapeutic approaches. RCTs have been developed to investigate the use of transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) to treat AN, with promising improvements in mood, restriction behaviors, body image, and subsequently BMI [79, 80]. Electroencephalography (EEG)-based neurofeedback has also been explored, demonstrating potential therapeutic benefits in this population [81]. Notably, deep brain stimulation (DBS) has been investigated in the treatment of AN, primarily in individuals with longstanding, treatment-refractory illness. A systematic review of DBS for AN reported favorable outcomes, including increases in BMI and improvements in quality of life [79]. Lastly, virtual reality (VR)-based interventions have shown preliminary efficacy in reducing body dissatisfaction and attenuating fear of weight gain [79]. While current evidence appears to support the safety and tolerability of neuromodulation and VR interventions in AN, replication of efficacy in larger, controlled trials remains necessary [82, 83].

Advances in Pharmacological Treatment of Binge Eating Disorder

A total of 27 clinical trials were identified investigating the effect of an agent in the treatment of BED from 1 January 2010 to 1 January 2025. Agents tested included central nervous system (CNS) stimulants, nonstimulant catecholaminergic drugs, combination therapies, serotonergic agents, opioidergic drugs, and neurohormone modulators. Of these trials, 16 were later-stage trials (phase 3 or 4), which primarily investigated CNS stimulants, nonstimulant catecholaminergic medications, and combination therapies. A summary of identified trials for the treatment of BED is presented in Table 2, sorted by medication class. A summary of each agent tested is presented in Supplementary Table 2, including mechanisms of action, dosing information, clinical trial phase, and notes to clinicians.

Table 2.

Summary of clinical trials for binge eating disorder (2010–2025)

NCT registry number	Active interventions (dose)	Control groups	Trial phase, design	N	Start year	End year (actual/estimated)	Sponsor	Primary outcomes	Main findings
CNS stimulants
NCT01657019	Lisdexamfetamine 50–70 mg/day	N/A (open label)	Phase 3, open-label single-group trial	604	2012	2014 (actual)	Takeda (Shire)	Percentage of participants with TEAEs, 52 weeks; number of participants with a positive response on the C-SSRS, 53 weeks	Of the 604 participants enrolled, 369 completed the study, with most receiving LDX treatment for 12 months or longer. The primary findings indicated that 84.5% of participants experienced TEAEs , with dry mouth, headache, insomnia, and upper respiratory tract infection being the most frequently reported, while no suicidal behaviors or completed suicides were observed
NCT03924193 [84]	Lisdexamfetamine + CBT 30–70 mg/day	CBT only	Phase 3 single-blind parallel group RCT	141	2019	2023 (actual)	Yale University	BE frequency (post-treatment, 3 months); change in BMI (post-treatment, 3 months)	BE frequency and eating-disorder psychopathology significantly decreased across all treatments, with CBT+LDX showing the greatest reductions and outperforming CBT and LDX. CBT+LDX also led to the highest binge-eating remission rates and significant weight loss, followed by LDX, while CBT alone had minimal impact on weight outcomes
NCT01090713	Lisdexamfetamine 20–70 mg/day	Placebo	Phase 3 double-blind parallel group RCT	50	2010	2012 (actual)	Lindner Center of HOPE	Frequency of BE episodes, 12 weeks	Pending (trial is completed)
NCT01718509 [85]	Lisdexamfetamine 50–70 mg/day	Placebo	Phase 3 double-blind parallel group RCT	390	2012	2013 (actual)	Takeda (Shire)	Change from baseline in number of BE days per week at visit 8 (weeks 11/12), as assessed by clinical interview on the basis of subject binge diary	Lisdexamfetamine dimesylate was superior to placebo in reducing BE days per week
NCT01718483 [85]	Lisdexamfetamine 50–70 mg/day	Placebo	Phase 3 double-blind parallel group RCT	383	2012	2013 (actual)	Takeda (Shire)	Change from baseline in number of BE days per week at visit 8 (weeks 11/12), as assessed by clinical interview on the basis of subject binge diary	Lisdexamfetamine dimesylate demonstrated superiority over placebo in reducing BE days per week in adults with BED
NCT02009163 [86]	Lisdexamfetamine 50–70 mg/day	Placebo	Phase 3 double-blind parallel group RCT	418	2014	2015 (actual)	Takeda (Shire)	Time to relapse (date of randomization to endpoint of randomized-withdrawal period), relapse status (double-blind treatment phase), BE (self-report diary), CGI-S (Visit 21, 26 weeks after randomization)	Lisdexamfetamine significantly reduced the risk of relapse compared with placebo in participants meeting relapse criteria during the randomized phase of the study
NCT01291173 [87]	Lisdexamfetamine 30–70 mg/day	Placebo	Phase 2 double-blind parallel group RCT	271	2011	2012 (actual)	Takeda (Shire)	Change from baseline in log transformed BE days per week, week 11	The 50 and 70 mg/d treatment groups were effective in reducing BE days and achieving BE cessation compared to the placebo group. No such improvements were observed in the 30 mg/day treatment group
NCT03926052 [84]	Lisdexamfetamine 30–70 mg/day	Placebo	Phase 3 double-blind parallel group RCT	80	2019	2023 (actual)	Yale University	BE relapse (eating disorder examination interview, ≥ 4 episodes/month), baseline to 3 months, post-treatment to 6 months, post-treatment to 12 months	Maintenance LDX and placebo did not differ significantly in BE remission or relapse rates, but they differed in weight-change and eating-disorder psychopathology outcomes. LDX was associated with weight loss and stable psychopathology, while placebo led to weight gain and increased psychopathology
NCT01921582 [88]	Methylphenidate 18–72 mg	CBT only	Phase 2, single-blinded parallel group trial	51	2013	2015 (actual)	Centre for Addiction and Mental Health	Frequency of BE episodes/days, as assessed by prospective daily binge diary, after 12 weeks of treatment	Both methylphenidate and CBT significantly reduced the frequency of BE episodes; methylphenidate was associated with greater decreases in BMI, compared with CBT
Nonstimulant catecholaminergic agents
NCT05118906	BP1.4979 15 mg/twice daily	Placebo	Phase 2, double-blind parallel group RCT	66	2022	2025 (estimated)	Bioprojet	Number of BE episodes per week as measured during baseline and at the end of the treatment period, 8 weeks	Pending (trial is active)
NCT05113953	Centanafadine 200–400 mg daily	Placebo	Phase 2, double-blind parallel group RCT	147	2021	2022 (actual)	Otsuka Pharmaceutical Development & Commercialization, Inc.	Change from baseline in number of BE days per week, baseline to week 8	Pending (trial is completed)
NCT02684279	Dasotraline 4–8 mg/day	N/A (open label)	Phase 3, open-label single-group trial	533	2016	2019 (actual)	Sumitomo Pharma America, Inc.	Frequency and severity of suicidal ideation (C-SSRS), baseline to week 52; frequency and severity of suicidal behavior (C-SSRS), baseline to week 52	Majority of patients with BED treated with dasotraline experienced no suicidal ideation per the C-SSRS (515/527) or suicide attempts (525/527)
NCT02564588 [89]	Dasotraline 4–8 mg/day	Placebo	Phase 3 double-blind parallel group RCT	319	2015	2016 (actual)	Sumitomo Pharma America, Inc.	Change from baseline in number of BE days (defined as days during which at least 1 BE episode occurs) per week to week 12, 12 weeks	Dasotraline treatment resulted in greater reductions in weekly BE days and notable improvements in illness severity, BE symptoms, and cessation rates over 4 weeks compared with placebo
NCT03107026 [90]	Dasotraline 4–6 mg	Placebo	Phase 3 double-blind parallel group RCT	491	2017	2018 (actual)	Sumitomo Pharma America, Inc.	Change from baseline in number of BE days, 12 weeks	Dasotraline 6 mg/day significantly reduced the frequency of BE days per week, while the 4 mg/day dose did not demonstrate efficacy. Both doses improved scores on the YBOCS-BE and BE-CGI-S. Dasotraline was generally safe and well tolerated
NCT04602936	Solriamfetol 37.5–150 mg/day	Placebo	Phase 4 double-blind parallel group RCT	64	2021	2024 (estimated)	Lindner Center of HOPE	BE day frequency as assessed by the take-home patient diary; days with BE episodes, days 1–84	Pending (trial is active)
NCT06413433	Solriamfetol 50–300 mg/day	Placebo	Phase 3 double-blind parallel group RCT	450	2024	2025 (estimated)	Axsome Therapeutics, Inc.	Change from baseline to week 12 in number of BE episodes, 12 weeks	Pending (trial is active)
Combination pharmacotherapy
NCT03045341 [91]	Bupropion 360 mg/day + naltrexone 32 mg/day	Placebo + behavioral weight loss (BWL) counseling, placebo only, BWL only	Phase 3, double-blind balanced factorial (2 × 2) design RCT	136	2017	2022 (actual)	Yale University	BE frequency, post-treatment (4 months); BMI, post-treatment (4 months)	Naltrexone-bupropion was significantly superior to placebo and BWL counseling was superior to no BWL in improving BE remission rates. However, there was no significant interaction between BWL and medication
NCT03539900 [92]	Bupropion 360 mg/day + naltrexone 32 mg/day	Placebo	Phase 3 double-blind parallel group RCT	89	2018	2023 (actual)	Yale University	Change in BE frequency post-treatment, (3 months); percent BMI change post-treatment (3 months)	Both naltrexone/bupropion and placebo led to significant reductions in BE frequency, though there were no significant differences between groups. The naltrexone/bupropion group had a significantly higher rate of attaining ≥ 5% weight loss than placebo (27.9% versus 6.5%)
NCT03047005	Bupropion 360 mg/day + naltrexone 32 mg/day	Placebo	Phase 3 double-blind parallel group RCT	68	2017	2022 (actual)	Yale University	BE frequency (continuous), post-treatment (4 months); change in BMI, baseline and post-treatment (4 months)	BE frequency was reduced in the naltrexone-bupropion medication group compared with placebo at post-treatment, though the difference did not reach statistical significance (P = 0.07). Participants receiving naltrexone-bupropion medication showed a greater reduction in BMI compared with placebo (P = 0.01)
NCT03946111	Bupropion 360 mg/day + naltrexone 32 mg/day	Placebo	Phase 3 double-blind parallel group RCT	3	2019	2024 (estimated)	Yale University	BE frequency (continuous), post-treatment (4 months); change in BMI, baseline and post-treatment (4 months)	Pending (trial is active)
NCT02659475 [93]	Phentermine 3.75–7.5 mg / Topiramate 23–46 mg daily	N/A (open label)	Phase 2, open-label single-group trial	10	2015	2016 (actual)	Lindner Center of HOPE	Change in weight, weeks 2, 4, 6, 8, 10, and 12 from baseline visit (week 0) to final visit or early termination	Phentermine–topiramate treatment led to significant weight loss and reduction in BE episodes in participants with BED and obesity or overweight. The drug combination also improved clinical severity and eating disorder psychopathology without SAEs
NCT02553824 [94]	Phentermine 3.75–15 mg / topiramate 23–92 mg daily	Placebo	Phase 1 double-blind crossover trial	22	2015	2017 (actual)	Stanford University	Frequency of BE episodes as measured by the EDE, 8.5 months	Phentermine-topiramate significantly reduced BE episodes compared with placebo and was well tolerated with minimal side effects. However, findings related to safety and efficacy in individuals with bulimia nervosa should be interpreted cautiously due to the small sample size for this subgroup
Serotonergic agents
NCT05035927	Psilocybin 25 mg	N/A (open label)	Phase 2, open-label single-group trial	5	2022	2024 (actual)	TRYP Therapeutics	AEs, SAEs, safety labs, vital signs, and other tests, 12 weeks following dosing	Pending (trial is completed)
NCT02528409 [95]	Vortioxetine 10–20 mg/day	Placebo	Phase 2 double-blind parallel group RCT	80	2016	2018 (actual)	University of Chicago	Change in number of BE episodes, from week 0 (baseline) to the final visit (week 12)	Vortioxetine and placebo both resulted in significant reductions in BE frequency, with no significant differences observed between the groups on any efficacy measure
Opioidergic agents
NCT01098435 [96]	Samidorphan 10 mg	Placebo	Phase 2 double-blind parallel group RCT	69	2010	2011 (actual)	Alkermes, Inc.	Number of participants in each dose group reporting at least one TEAE, 6 weeks	Treatment with samidorphan over a 6-week period failed to separate from placebo in decreasing the frequency of BE episodes
Neurohormone modulators
NCT04753164 [97]	Nivasorexant 100 mg/twice daily	Placebo	Phase 2, double-blind parallel group RCT	136	2021	2022 (actual)	Idorsia Pharmaceuticals Ltd.	Change in BE days per week from baseline to week 12 (duration ~ 3.5 months)	Nivasorexant did not demonstrate a significant difference from placebo in reducing the number of BE days per week from baseline to week 12
NCT05664516	Oxytocin (dose is unknown)	Placebo	Phase 2, double-blind parallel group RCT	60	2023	2024 (estimated)	Massachusetts General Hospital	Weight (kg), change from baseline in weight, 8 weeks	Pending (trial is active)

Each agent in the BED clinical trials above is described in detail in the main text, sorted by class

AEs adverse events, BE binge eating, BE-CGI-S Binge Eating Clinical Global Impression-Severity, BED binge eating disorder, BMI body mass index, BWL behavioral weight loss, CBT cognitive behavioral therapy, C-SSRS Columbia-Suicide Severity Rating Scale, CGI-S Clinical Global Impression-Severity, CNS central nervous system, EDE Eating Disorder Examination, IV intravenous, LDX lisdexamfetamine dimesylate, NCT National Clinical Trial (identifier number), RCT randomized controlled trial, SAEs serious adverse events, TEAE treatment-emergent adverse event, YBOCS-BE Yale–Brown Obsessive Compulsive Scale–Binge Eating

CNS Stimulants in Binge Eating Disorder

A total of two CNS stimulants, including lisdexamfetamine dimesylate and methylphenidate, were investigated in BED during this period, comprising nine clinical trials, the majority of which were in phase 3. Among these, lisdexamfetamine dimesylate (LDX) (Vyvanse^®) has been the subject of significant investigation and is the first drug to receive FDA approval for BED [98].

As a prodrug, LDX consists of dextroamphetamine bound to the amino acid l-lysine [99]. Following administration, enzymatic hydrolysis of this bond functions as a rate-limiting step, permitting a duration of action of 13+ h post-dose [99]. Pharmacodynamically, LDX acts as both a releasing agent and competitive reuptake inhibitor of dopamine, norepinephrine, and to a lesser extent, serotonin. These mechanisms contribute to appetite suppression, attenuation of reward sensitivity, and improved goal-directed cognitive control, which are believed to underlie its efficacy in BED [98, 100].

Two phase 3 randomized controlled trials found that 50 mg and 70 mg of LDX produced statistically significant decreases in binge eating days/week relative to placebo in adults with moderate-to-severe BED (least square means change [LSMC] − 3.9 versus − 2.5 in study 1, − 3.9 versus − 2.3 in study 2) [85]. LDX was also associated with a statistically significant and clinically meaningful greater response on outcomes of global improvement in BED pathology, 4-week cessation of binge eating at the endpoint, and BED-related obsessive and compulsive psychopathology [85]. As a Schedule II controlled substance, it should be noted that LDX carries risk for stimulant use disorder [101]. Common adverse effects of LDX include xerostomia, headache, and insomnia [102].

In addition to LDX, methylphenidate (Ritalin®, Concerta®) has also been evaluated as a potential treatment for BED and is FDA approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) [103]. As a reuptake inhibitor of dopamine and norepinephrine, methylphenidate has been investigated in the treatment of several conditions, including binge eating disorder, depressive disorders, and substance use disorders, among others [88, 103, 104]. In a phase 2 RCT, long-acting methylphenidate was compared with cognitive behavioral therapy (CBT) in the treatment of BED [88]. Both interventions significantly reduced the frequency of binge episodes and improved secondary outcomes such as body mass index (BMI) and quality of life. Methylphenidate was associated with greater decreases in BMI compared with CBT [88]. As with other stimulants, methylphenidate is classified as a Schedule II controlled substance with potential for misuse [105]. Reported treatment-emergent effects include insomnia, anxiety, headache, xerostomia, and other sympathomimetic side effects [106].

Nonstimulant Catecholaminergic Agents in Binge Eating Disorder

A total of four unique nonstimulant catecholaminergic drugs were investigated in BED during this period, comprising seven clinical trials in phases 2, 3, and 4. Among these are novel and repurposed agents, including BP1.4979, centanafadine, dasotraline, and solriamfetol.

BP1.4979 is a selective partial agonist at the dopamine D3 receptor [107]. It entered a phase 2 placebo-controlled, double-blind clinical trial for the treatment of binge eating disorder in 2022, with participants receiving an oral dose of 15 mg twice daily. No results were identified from completed trials investigating BP1.4979 in BED. However, the current study (n = 66) has an estimated completion date in late 2025. Commonly reported adverse effects include headache, fatigue, lack of sleep, and increased dream activity [107].

Centanafadine (EB-1020) is an orally administered reuptake inhibitor of serotonin, dopamine, and norepinephrine under development for the treatment of BED and ADHD [108]. In BED, centanafadine was evaluated in a single phase 2 clinical trial (n = 147) in which participants received oral doses of 200 mg twice daily. To date, results could not be identified from this trial, which was completed in late 2022. Documented adverse effects of centanafadine include gastrointestinal disorders, diarrhea, xerostomia, nausea, decreased appetite, and headache [108].

Dasotraline (SEP-225289) is an orally administered reuptake inhibitor of serotonin, dopamine, and norepinephrine that has been investigated in several phase 3 trials for the treatment of BED and ADHD [89, 109, 110]. Unlike its stereoisomer, desmethylsertraline (an active metabolite of sertraline), dasotraline inhibits the dopamine transporter (DAT) most strongly (IC₅₀ 3 nM), followed by the norepinephrine transporter (NET; IC₅₀ 4 nM), and is a relatively weaker inhibitor of the serotonin transporter (SERT; IC₅₀ 15 nM) [110]. In 2020, however, development was halted for this indication, and its accepted New Drug Application (NDA) with the FDA was withdrawn, citing a need for more trials [111].

In a phase 3 randomized, placebo-controlled, flexible-dose clinical trial in patients with BED (N = 315), dasotraline (4, 6, or 8 mg) significantly reduced the number of binge-eating days per week compared with placebo (least squares mean difference score, − 0.99; P < 0.0001; effect size, 0.74) [89]. Significant improvements were also observed in the Clinical Global Impressions-Severity of Illness scale (CGI-S) and the Yale–Brown Obsessive Compulsive Scale Modified for Binge-Eating (YBOCS-BE), with effect sizes of 0.95 and 0.96, respectively. Common adverse events included insomnia, dry mouth, decreased appetite, and anxiety, with a discontinuation rate due to adverse events of 11.3% for dasotraline versus 2.5% for placebo. In a second phase 3 RCT, dasotraline was evaluated at doses of 4 mg/day and 6 mg/day [109]. The 6 mg/day dose (N = 162) was associated with a significant reduction in binge-eating days per week compared with placebo (− 3.47 versus − 2.92; P = 0.0045), though this was not the case for the 4 mg/day dose (N = 161; 3.21 versus. − 2.92; P = 0.119). Both doses showed improvements in the BE-CGI-S and YBOCS-BE scores, with effect sizes of 0.37 and 0.27 for BE-CGI-S, and 0.43 and 0.29 for YBOCS-BE, respectively.

Solriamfetol (Sunosi^®) is an orally administered norepinephrine–dopamine reuptake inhibitor (NDRI) approved by the FDA for the treatment of excessive daytime sleepiness in narcolepsy or obstructive sleep apnea (OSA) [112]. A phase 3 randomized, placebo-controlled, double-blind trial was initiated in 2024 to investigate its efficacy in BED. Solriamfetol shares a pharmacologic mechanism with other agents evaluated in BED, such as dasotraline, and is hypothesized to reduce binge-eating behavior through modulation of catecholaminergic signaling [113]. Of note, solriamfetol is a Schedule IV controlled substance with an abuse potential similar to or lower than phentermine [114].

In patients with narcolepsy, solriamfetol has been associated with short-term and long-term weight loss. Among two 12-week randomized, placebo-controlled trials, the proportion of participants achieving ≥ 5% weight reduction at week 12 was 0% with placebo, 10.2% with 75 mg/day, 6.0% with 150 mg/day, and 7.0% with 300 mg/day doses of solriamfetol [115]. These weight reductions are believed to potentially contribute to improvement of BED symptomatology. Given the established association between narcolepsy and binge-eating behavior, these findings support further investigation into solriamfetol’s potential as a treatment for BED [113, 116]. Reported adverse effects of solriamfetol include agitation, headache, and dizziness [113].

Combination Pharmacotherapy in Binge Eating Disorder

A total of two unique combination therapies were investigated in BED during this period, comprising six clinical trials in phases 1, 2, and 3. These agents include combination preparations of naltrexone and bupropion, as well as phentermine and topiramate.

Naltrexone/bupropion (NB) is an orally administered combination therapy approved by the FDA for the treatment of obesity [117]. Bupropion, a norepinephrine–dopamine reuptake inhibitor (NDRI), activates pro-opiomelanocortin (POMC) neurons in the hypothalamus, which suppress appetite and increase energy expenditure [118]. Concurrently, naltrexone blocks inhibitory feedback on POMC neurons, prolonging their activation and enhancing their appetite-suppressant effects [119]. Through these mechanisms, NB is hypothesized to regulate food intake and reduce binge eating behavior [92, 119]. Preliminary findings from a prospective, randomized, double-blind, placebo-controlled trial demonstrated higher binge-eating remission rates during maintenance treatment with NB compared with placebo (68.8% versus 50.0%) [92]. Following acute treatment response, continuing with placebo was linked to a significant decrease in binge-eating remission rates, increased frequency of binge-eating episodes, and no weight loss. Conversely, continuing with naltrexone/bupropion maintained high rates of binge-eating remission, reduced frequency of binge-eating episodes, and led to additional significant weight loss. Commonly reported adverse effects of NB include nausea, headache, xerostomia, and constipation [120].

Phentermine/topiramate combination therapy (Qsymia^®) is FDA approved to aid in the reduction of excess body weight and support long-term weight maintenance when combined with a reduced-calorie diet and physical activity [93]. Phentermine is an orally administered amine sympathomimetic that functions as both a releasing agent and reuptake inhibitor, namely of norepinephrine and dopamine [121]. As a Schedule IV controlled substance, it should be noted that phentermine has potential for misuse [122]. Topiramate is an anticonvulsant and voltage-dependent sodium channel blocker that is FDA approved for the treatment of epilepsy (as monotherapy and adjunctive therapy) and prophylaxis of migraine headaches [123]. Adverse effects of phentermine/topiramate include dysgeusia, paresthesia, xerostomia, attentional disturbances, irritability, hypoesthesia, constipation, and dizziness [124].

In a placebo-controlled RCT, 22 adults with BED or BN were treated with phentermine/topiramate extended-release (ER) at doses ranging from 3.75 mg/23 mg to 15 mg/92 mg [94]. The primary outcome, objective binge-eating (OBE) days over 4 weeks, significantly decreased from a baseline of 16.2 days (SD 7.8) to 4.2 days (SD 8.4) with phentermine/topiramate ER, compared with 13.2 days (SD 9.1) with placebo (P < 0.0001). Additionally, the abstinence rate from binge eating was 63.6% with phentermine/topiramate ER versus 9.1% with placebo (P < 0.0001). Weight loss was also observed, with a mean reduction of 5.8 kg on phentermine/topiramate ER compared with a gain of 0.4 kg on placebo. The dropout rate was 9% for both groups, and side effects were minimal and comparable with placebo [94].

Serotonergic Agents in Binge Eating Disorder

A total of two unique serotonergic agents were investigated in BED during this period, comprising two clinical trials, all of which were phase 2. These agents include psilocybin and the multimodal antidepressant vortioxetine.

Psilocybin is an orally administered psychedelic, which functions as a prodrug of psilocin and is thought to produce its psychotropic effects via biased agonism at the serotonin 5-HT2A receptor [49, 50]. Psilocybin has been investigated with positive results in the treatment of major depression, anxiety disorders, and substance use disorders [51, 125]. It completed a phase 2 RCT for the treatment of BED in 2021, and trial results are pending. No other trial results from RCTs investigating the efficacy of psilocybin in BED were identified. Documented adverse effects of psilocybin include nausea, anxiety, dizziness, and elevated blood pressure [54].

Vortioxetine is an antidepressant approved by the FDA for the treatment of major depression. It functions as a serotonin modulator and stimulator, primarily through inhibition of the serotonin transporter and modulation of various serotonin receptors, including 5-HT1A agonism and 5-HT3 antagonism [126]. In a placebo-controlled, double-blind, phase 2 RCT, both vortioxetine and placebo significantly reduced binge eating frequency in adults with BED [95]. There were no significant differences between groups on any efficacy measure. Reported adverse effects of vortioxetine include nausea, diarrhea, xerostomia, and headaches [127].

Opioidergic Agents in Binge Eating Disorder

One opioidergic agent, samidorphan, was investigated in BED during this period. Samidorphan is a μ-opioid receptor (MOR) antagonist that has been primarily studied in combination with olanzapine to mitigate weight gain associated with antipsychotic treatment in schizophrenia and bipolar I disorder [128]. As MOR agonism is known to enhance the reward value of flavors, it was hypothesized that samidorphan would have clinical utility in the treatment of BED [96, 129]. In a phase 2 double-blind, placebo-controlled trial, 6 weeks of treatment with samidorphan and placebo led to large decreases in the frequency of binge eating episodes [96]. However, samidorphan failed to significantly outperform placebo in any outcome measure in the treatment of BED. Reported adverse effects include somnolence, nausea, constipation, and decreased appetite [130].

Neurohormone Modulators in Binge Eating Disorder

A total of two unique neurohormone modulators were investigated in BED during this period, comprising two clinical trials, both of which were phase 2. Nivasorexant (ACT-539313) is an orally administered, selective orexin-1 receptor (OX1R) antagonist that has been investigated for its potential use in the treatment of BED [97, 131]. As one of the first identified selective orexin-1 receptor antagonists investigated in clinical trials, it may confer therapeutic benefits without inducing the degree of sleep premotion observed with dual orexin receptor antagonists (DORAs) [131]. It entered a phase 2 placebo-controlled RCT to investigate its efficacy in the treatment of BED in 2022 [97]. However, 12 weeks of therapy with nivasorexant failed to separate from placebo in reducing the number of binge eating days per week. Likewise, there were no significant between-group differences in secondary outcome measures, though nivasorexant was well tolerated [97]. Reported adverse effects include headache, nausea, decreased appetite, and possible somnolence [132].

TNX-1900 is a proprietary intranasal formulation of oxytocin undergoing phase 2 clinical trials for the treatment of binge eating disorder and obesity. Oxytocin, a hypothalamic peptide hormone, is known for its roles in labor, lactation, and social behavior [133, 134]. A phase 2 placebo-controlled RCT investigating intranasal oxytocin in the management of binge eating disorder (n = 60) began in 2023 and is currently ongoing. A meta-analysis by Chen et al. (2021) reviewed 12 controlled trials and found that single-dose intranasal oxytocin significantly reduced food intake in non-psychiatric subjects (standardized mean difference, SMD − 0.66 [95% CI − 1.18, − 0.14]). However, no significant effects were observed in patients with BN and BED (SMD − 0.41 [95% CI − 0.94, 0.11]) [135]. Notably, oxytocin does not appear reliably associated with significant adverse effects when acutely delivered in research settings [136].

Challenges, Clinical Implications, and Future Directions

One of the few significant developments during this period was the approval of lisdexamfetamine dimesylate (Vyvanse) for the treatment of BED in 2015, marking the first medication approved for this indication. As of January 2025, it is one of two drugs approved by the FDA for any ED, alongside fluoxetine for the management of BN [30]. Following the approval of lisdexamfetamine for BED, it has become integrated into current practice guidelines. The APA recommends that patients with BED receive eating-disorder-focused cognitive behavioral therapy (CBT) or interpersonal therapy (IPT) as first-line treatment, offered in either individual or group settings [32]. For adult patients with BED who prefer pharmacotherapy or have not responded to psychotherapy alone, the APA suggests the use of pharmacological options, including lisdexamfetamine and antidepressants [32]. Both antidepressants and lisdexamfetamine have demonstrated efficacy in reducing binge frequency in patients with BED relative to placebo [29]. Meta-analytic findings indicate that antidepressants are associated with a small effect size (standardized mean difference = − 0.29; 95% CI − 0.51, − 0.06), while lisdexamfetamine exhibits a medium effect size (Hedges’ g = 0.57; 95% CI 0.28–0.86) in reducing binge episodes [29, 137, 138].

Apart from the approval of lisdexamfetamine, little progress has been made in the development of medications for BED. Of the 14 agents investigated in BED, a total of 3 (besides lisdexamfetamine) were in late-stage trials (phase 3 or 4), including solriamfetol, dasotraline, and bupropion/naltrexone. Of these, few had positive results and remain in development as of January 2025.

In particular, solriamfetol, a norepinephrine and dopamine reuptake inhibitor, appears to be one of the more promising investigative agents, with results pending from a large phase 3 trial initiated in 2024. Additionally, it may be noted that combination therapy with the norepinephrine–dopamine reuptake inhibitor bupropion and the opioid receptor antagonist naltrexone was consistently superior to placebo in promoting weight loss, though not reducing binge eating frequency in individuals with BED.

Other agents are used off label in the treatment of BED, despite a lack of recent identified clinical trials to confirm their potential therapeutic benefit. Topiramate, an antiepileptic drug with FDA approval for epilepsy and migraines, is often prescribed for the treatment of BED. A 2003 randomized placebo-controlled trial found that topiramate significantly reduced binge frequency (94% versus 46%) and binge day frequency (93% versus 46%) compared with placebo, demonstrating a notably higher response rate [139]. A 2021 systematic review and meta-analysis published in CNS Spectrums found topiramate to significantly outperform placebo in reducing binge episodes per week, binge days per week, and weight among three trials [140]. However, participants receiving topiramate exhibited a significantly higher rate of withdrawal attributable to adverse effects, most commonly headache, paresthesia, somnolence, and nausea [140]. More recently, topiramate has been explored in combination with LDX for the treatment of BED. A 2024 randomized control trial found that 3 months of combination therapy with LDX and topiramate significantly decreased Binge Eating Scale (BES) scores and improved metabolic markers compared with patients treated with LDX alone [141]. Future research may aim to evaluate the long-term efficacy, safety profile, and optimal dosing strategies of topiramate monotherapy and polytherapy in BED.

Novel pharmacotherapy with glucagon-like peptide-1 (GLP-1) may also provide benefit given increasing evidence that GLP-1 may play an important role in binge eating [142]. A retrospective cohort study in 2023 found that in patients with BED, treatment with GLP-1 analog semaglutide alone resulted in significantly lower BES scores compared with patients receiving lisdexamfetamine and topiramate [143]. In addition, in a pilot randomized controlled trial (n = 27), treatment with liraglutide was associated with greater percent weight loss relative to placebo (5.2 ± 1.0% versus 0.9 ± 0.7%, P = 0.005), though there was no statistically significant difference in BED remission rates between groups (44% versus 36%) [144]. Further studies are needed to fully understand the effects of GLP-1 agonists in BED.

Recent investigations have also evaluated nonpharmacologic interventions for BED. Preliminary studies of tDCS have demonstrated superiority over sham stimulation in reducing cravings and binging [145]. Likewise, rTMS and neurofeedback have been proposed as potential strategies to attenuate binge-eating behaviors [79, 81, 145]. VR-based interventions have also been examined, although findings remain inconsistent [79]. The mechanisms underlying these approaches are not fully elucidated, and further controlled trials are warranted to clarify their efficacy and integration with pharmacologic treatments.

Advances in Pharmacological Treatment of Bulimia Nervosa

A total of two identified trials investigated the effect of a pharmacotherapeutic intervention on BN from 1 January 2010 to 1 January 2025. A summary of these trials is presented in Table 3, and a summary of identified agents is presented in Supplementary Table 3.

Table 3.

Summary of clinical trials for bulimia nervosa (2010–2025)

NCT registry number	Active drug (dose)	Control groups	Trial phase, design	N	Start year	End year (actual/estimated)	Sponsor	Primary outcomes	Main findings
Combination pharmacotherapy
NCT04225221	Estradiol 2 mg/twice daily; progesterone 2 mg/twice daily	Placebo	Phase 2 double-blind crossover trial	10	2020	2022 (actual)	University of North Carolina, Chapel Hill	Change in 8-item binge eating subscale of the EPSI, change in weekly average BE frequency; baseline to end of intervention (D14 of intervention)	BE symptoms, assessed using the EPSI BE subscale, decreased in the estradiol group but increased slightly in the progesterone group from baseline to the end of the intervention. Similarly, self-reported weekly BE episodes declined in the estradiol group, while they increased in the progesterone group over the same period
NCT02553824 [94]	Phentermine 3.75–15 mg/topiramate 23–92 mg daily	Placebo	Phase 1 double-blind crossover trial	22	2015	2017 (actual)	Stanford University	Frequency of BE episodes as measured by the EDE, 8.5 months	PHEN/TPM-ER significantly reduced BE episodes compared with placebo and was well tolerated with minimal side effects. However, findings related to safety and efficacy in individuals with bulimia nervosa should be interpreted cautiously due to the small sample size for this subgroup

Each agent in the bulimia nervosa clinical trials above is described in detail in the main text, sorted by class

BE binge eating, BMI body mass index, BN bulimia nervosa, D day, EDE Eating Disorder Examination, EPSI Eating Pathology Symptoms Inventory, NCT National Clinical Trial (identifier number), PHEN/TPM-ER phentermine/topiramate extended-release, RCT randomized controlled trial

Combination Pharmacotherapy in Bulimia Nervosa

Combination therapy with estradiol, progesterone, and leuprolide acetate has been investigated in BN. Estradiol, a primary estrogen produced by the ovaries, is FDA approved for managing menopausal symptoms, treating hypoestrogenism, and as a component of hormone replacement therapy (HRT) [146, 147]. Progesterone is a naturally occurring steroid hormone commonly used in HRT to counteract the effects of estrogen [148]. Leuprolide acetate is a synthetic nonapeptide and potent gonadotropin-releasing hormone (GnRH) receptor agonist that reduces the production of gonadal sex steroids in the treatment of prostate cancer, endometriosis, and precocious puberty [149]. Estradiol, progesterone, and leuprolide acetate have been investigated in BN in a phase 2 crossover trial. Eating symptoms, measured with the Eating Pathology Symptoms Inventory (EPSI) binge eating subscale, decreased in the group that began with estradiol followed by progesterone. In contrast, these symptoms slightly increased in the group that started with progesterone, followed by estradiol. Likewise, self-reported weekly binge-eating episodes declined in the estradiol-first group but rose in the progesterone-first group during the same period. Reported adverse effects of the trial included hot flashes, headache, insomnia, spotting, and bloating.

The combination of phentermine and topiramate, under the brand name Qsymia^®, is FDA approved for weight reduction and long-term weight management as an adjunct to a calorie-restricted diet and increased physical activity [93]. Phentermine is a monoamine reuptake inhibitor and releasing agent, mainly targeting noradrenergic and dopaminergic neurons, and is a Schedule IV controlled substance [121]. Topiramate, an anticonvulsant and voltage-gated sodium channel blocker, is approved by the FDA for the treatment of epilepsy and for migraine prevention [123]. Reported adverse effects of the phentermine/topiramate combination include dysgeusia, paresthesia, xerostomia, attentional disturbances, irritability, hypoesthesia, constipation, and dizziness [124].

In a randomized, placebo-controlled trial, 22 adults with BED or BN received extended-release phentermine/topiramate at doses ranging from 3.75 mg/23 mg to 15 mg/92 mg [94]. The primary endpoint, the number of objective binge-eating (OBE) days over 4 weeks, was significantly reduced from a baseline mean of 16.2 days (SD 7.8) to 4.2 days (SD 8.4) in the active treatment group, compared with 13.2 days (SD 9.1) in the placebo group (P < 0.0001). The abstinence rate from binge eating was 63.6% in the phentermine/topiramate ER group versus 9.1% with placebo (P < 0.0001). Weight reduction was also observed, with a mean loss of 5.8 kg in the active group compared with a mean gain of 0.4 kg with placebo. Dropout rates were similar between groups (9%), and adverse events were minimal and comparable to placebo [94].

Challenges, Clinical Implications, and Future Directions

Recent pharmacological research for BN is particularly sparse. We identified only two trials, both of which were in the early stages. One trial investigated the efficacy of combination treatment with phentermine and topiramate in patients with BN and BED [94]. However, it was reported that of the 22 participants in the trial, only four had BN. In the other trial, researchers set out to understand the effect of estrogen and progesterone on symptoms of BN in ten women. Given the significantly underpowered nature of these trials, their findings provide limited insight into the efficacy of these treatments for BN. This is consistent with prior research suggesting significant limitations in the available data assessing pharmacotherapy in BN [138] and few new trials in recent years [150].

Fluoxetine is the only FDA-approved medication for BN. As a selective serotonin reuptake inhibitor (SSRI), fluoxetine was approved as an acute and maintenance treatment for BN in 1994 [30]. As first-line treatment for BN, the APA’s practice guidelines recommend the initiation of an SSRI alongside ED-focused cognitive-behavioral therapy [32]. Antidepressants, including fluoxetine, have been shown to reduce the frequency of binge eating episodes in patients with BN, with a small effect size (standardized mean difference = − 0.24; 95% CI − 0.41, − 0.08) [29, 138].

Several additional emerging interventions have been explored in the treatment of BN and warrant consideration as avenues for future research. The antiemetic ondansetron has also been used off label in BN, which, as a 5-HT3 receptor antagonist, acts to reduce afferent vagal neurotransmission and enhance satiety [151, 152]. Although research on ketamine in EDs is largely limited to AN, a case study into ketamine use for extreme BN refractory to all treatments at every level of care dramatically demonstrated complete and sustained remission [153]. Additionally, tDCS has been preliminarily investigated with some success in BN, and there is growing evidence to suggest that VR-based therapy may be effective [79, 82]. Nonetheless, the limited focus on BN in recent pharmacological research is concerning, given the disorder’s high prevalence and significant burden on health-related quality of life [154]. Future research may prioritize evaluation of these emerging and off-label interventions in rigorous clinical trials restricted to patients with bulimia nervosa.

Advances in Pharmacological Treatment of Other Eating Disorders

A total of two clinical trials were identified investigating the effect of an agent in the treatment of rumination disorder from 1 January 2010 to 1 January 2025. A summary of these trials is presented in Table 4, and a summary of identified agents in rumination syndrome is presented in Supplementary Table 4. No eligible trials were identified for the treatment of avoidant restrictive food intake disorder (ARFID), pica, other specified feeding or eating disorders (OSFED), or eating disorders not otherwise specified (EDNOS).

Table 4.

Summary of clinical trials for other eating disorders (2010–2025)

NCT registry number	Condition	Active drug (dose)	Control groups	Trial phase, design	N	Start year	End year (actual/estimated)	Sponsor	Primary outcomes	Main findings
NCT03113396 [155]	Rumination syndrome	Baclofen 10 mg/three times daily	Placebo	Phase 4 double-blind crossover trial	20	2012	2016 (actual)	Universitaire Ziekenhuizen KU Leuven	Overall well-being, assessed by Overall Treatment Evaluation Questionnaire, 2 weeks treatment	Baclofen significantly reduced regurgitation event markers, rumination episodes, and reflux events while increasing LES pressure and decreasing transient LES relaxations. Straining episodes remained similar, but the rumination-to-straining ratio and overall treatment effect favored baclofen over placebo
NCT05975684	Rumination syndrome	Baclofen 0.5 mg/kg/day	Placebo	Phase 3 double-blind parallel group RCT	50	2023	2024 (estimated)	Nationwide Children’s Hospital	Vomiting once a week or less (percentage of participants) assessed via Rumination Severity Survey at 4 weeks	Pending (trial is active)

The agent in the other eating disorders clinical trials above is described in detail in the main text

BMI body mass index, LES lower esophageal sphincter, NCT National Clinical Trial (identifier number), RCT randomized controlled trial

Rumination Syndrome

One drug, baclofen, was investigated in rumination disorder during this period, comprising two clinical trials in phases 3 and 4. Baclofen is an orally administered GABA(B) receptor agonist that is FDA approved for the treatment of muscle spasticity resulting from multiple sclerosis [156, 157]. In 2023, it entered phase 3 clinical trials for the treatment of rumination disorder in children, in addition to a phase 4 trial, which was completed in 2016. Reported adverse effects associated with baclofen include dyspeptic symptoms, dizziness, fatigue, and a lowered seizure threshold [158].

A phase 4 randomized double-blind, placebo-controlled, cross-over study included 20 patients with clinically suspected rumination syndrome and/or supragastric belching [155]. Participants received baclofen (10 mg, three times daily) or placebo for 2 weeks, with a 1-week washout period between treatments. The study found that baclofen significantly decreased the number of regurgitation events (median 6 versus 4, P = 0.04) and rumination episodes (median 13 versus 8, P = 0.004). Additionally, lower esophageal sphincter (LES) pressure was significantly higher after baclofen treatment (17.8 versus 13.1 mmHg, P = 0.0002), and the number of reflux events decreased (median 4 versus 3, P = 0.03). Overall treatment evaluation was superior with baclofen compared with placebo (P = 0.03) [155].

Challenges, Clinical Implications, and Future Directions

It is concerning that no eligible trials were identified assessing pharmacological interventions for the treatment of OSFED, ARFID, pica, or EDNOS. Available evidence for these populations remains largely anecdotal or based on retrospective chart reviews, small case series, open-label trials, or extrapolated from findings in better-studied disorders [159].

From a clinical perspective, this lack of robust data poses considerable challenges for treatment planning. Clinicians may be compelled to extrapolate from established evidence in AN, BN, or BED, which may not adequately reflect the unique psychopathology or medical risks inherent to OSFED and ARFID [160, 161]. For instance, appetite stimulants occasionally trialed in ARFID lack sufficient evaluation regarding long-term outcomes or the potential for adverse effects in medically fragile populations [162–164]. Similarly, SSRIs or atypical antipsychotics used in EDNOS or OSFED are often prescribed on the basis of comorbidity profiles (e.g., anxiety, depression, obsessive compulsive features) rather than eating pathology per se, leaving their specific role in core symptom reduction unclear [45, 165]. Future research should prioritize large, multisite RCTs that incorporate standardized diagnostic criteria, validated outcome measures, and long-term follow-up. Adaptive trial designs may be particularly well suited to these populations given the heterogeneity in symptom presentation.

Of note, emerging interest in pharmacological approaches for rumination disorder is reflected in a small number of trials. Rumination disorder is characterized by the repeated, effortless regurgitation of recently ingested food into the mouth, which may then be rechewed, reswallowed, or spat out, typically occurring within minutes of eating and without associated nausea, retching, or involuntary vomiting [166]. Rumination syndrome carries an overall global prevalence of 3.1% (95% CI 3.0–3.3%) and is associated with reduced quality of life [167]. Current treatment consists of diaphragmatic breathing and other behavioral interventions [166]. After positive results in a phase 4 trial investigating baclofen in rumination syndrome, a larger phase 3 trial was launched in 2023. We believe there is a compelling case for the continued investigation of baclofen for this indication.

Future Perspectives

Policy Implications

It has been argued that funding for eating disorder research does not align with the severity and public health needs associated with EDs [168]. In 2015, the volume of U.S. federal funding for eating disorder research amounted to approximately $0.73 per affected individual. In comparison, autism research received $58.65 per affected individual, and schizophrenia research was supported at a rate of $86.97 per affected individual [168]. This disparity may help to explain the persistent gap in evidence-based interventions for these complex and pernicious illnesses.

Progress in the development of novel pharmacotherapies is further constrained by limited understanding of the underlying pathophysiology of EDs [169, 170]. As a result, there are few clearly defined molecular targets for drug development in this area. Current treatments often repurpose medications developed for other psychiatric disorders, with variable efficacy and unclear mechanisms of action in ED populations. Advancing translational research aimed at identifying biologically plausible mediators and moderators of treatment response, such as specific neuroendocrine markers, brain circuit dysfunctions, or genetic variants, could support the discovery of more targeted and effective pharmacotherapies. Further research assessing the underlying pathophysiology of EDs is essential if novel agents are to be more than speculative in their promise.

EDs have some of the highest mortality rates of any psychiatric disorders [16], yet remain under-recognized by clinicians, leading to poor outcomes [171, 172]. For example, it is known that approximately 5% of patients die within 4 years of receiving a diagnosis of AN [16, 173]. This issue is exacerbated in diverse populations, which may not align with historical cultural stereotypes framing EDs as predominantly affecting affluent, young, white, cisgender women who appear severely underweight [174, 175]. Future research must account for the heterogeneity of ED presentations and prioritize the recruitment of diverse cohorts in clinical trials to ensure that interventions are effective across various demographic groups. Increased funding for clinical trials is essential to ensure that ED research reflects the true epidemiological scope of the disorder and leads to interventions that are accessible and beneficial for all.

Commercial and Regulatory Barriers

It should be noted that the small number of drugs with FDA-approved indications for eating disorders may reflect limited perceived commercial viability, as the FDA only reviews drug applications submitted by sponsors, in lieu of conducting independent evaluations of all potentially useful agents [176]. Compounds may show preliminary promise for the treatment of EDs, but lack the commercial incentives needed to sustain large-scale trials or pursue regulatory pathways, especially when patents are nearing expiration or off-label use already meets clinical demand. For example, other stimulants might possibly have comparable or even superior outcomes in BED compared with lisdexamfetamine, but without commercial drivers, these possibilities remain unexplored or unpublished. Alternatively, access to some novel agents may be limited by sponsor control or federal restrictions (e.g. psilocybin), rendering it difficult for independent researchers to initiate trials even when scientific rationale exists [177]. As such, the absence of FDA approval for a particular drug should not be interpreted as a definitive statement on its inefficacy. Our review takes care to identify peer-reviewed publications resulting from included clinical trials, which may serve as a more proximate indicator of an agent’s efficacy than FDA approval, given the longer timelines and higher perceived commercial demand required for regulatory authorization.

Limitations

This review has several limitations that must be acknowledged. The search strategy employed in this review focused primarily on clinical trials registered in the U.S. Clinical Trials Registry (ClinicalTrials.gov), which may lead to geographic biases despite the major inclusion of international trials in the registry. While efforts were made to include a broad range of clinical trials, a subset of studies conducted outside of the USA or those not registered might not have been captured. In employing a clinical trials registry to identify eligible studies, we sought to capture trials that may be in progress and reduce publication bias (i.e., against trials with null results that may remain unpublished elsewhere), though this approach is not all-encompassing.

As a narrative review derived from a systematic search of clinical drug trials, the synthesis of evidence relied primarily on qualitative description rather than quantitative aggregation. This approach reflected the substantial heterogeneity across the included studies, which varied markedly in trial design, sample populations, and outcome measures. Clinical trials may particularly vary in the strictness of their eligibility criteria. In early phase or registration-directed efficacy trials, particularly those aligned with regulatory approval efforts, it is common for sponsors to restrict enrollment to relatively homogeneous patient populations, excluding individuals with comorbid psychiatric diagnoses. In contrast, later-phase effectiveness trials, often at phase IV, may aim to reflect real-world treatment conditions and thus enroll more heterogeneous populations, including participants with concurrent diagnoses and those taking other medications. As a result of this heterogeneity, definitive conclusions may not be made regarding the comparative efficacy of different compounds under investigation.

Lastly, trials that were suspended, withdrawn, or prematurely terminated were not included in the review. While this approach aimed to enhance interpretability by focusing on active and completed studies, it may inadvertently omit relevant data from compounds that were deemed ineffective, associated with unacceptable safety concerns, or otherwise discontinued prior to trial completion.

Conclusions

Despite the high prevalence, morbidity, and mortality associated with eating disorders, the past 15 years have seen little advancement in pharmacological treatments. The approval of lisdexamfetamine for BED in 2015 remains the most notable development, yet few other compounds have progressed to late-stage clinical trials. Although emerging compounds, such as solriamfetol and bupropion/naltrexone for BED and psilocybin for AN, have shown preliminary promise, there remains a striking absence of FDA-approved medications for AN and no novel approvals for bulimia nervosa (BN) since fluoxetine in 1994. Research on BN is particularly sparse, with only two early phase trials identified in recent years and no pharmacological options under active late-stage investigation.

The dearth of clinical evidence for specific agents in EDs is mirrored in the World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines on the Pharmacological Treatment of Eating Disorders, last updated in 2023 [159]. The WFSBP posits only a limited recommendation for olanzapine in AN, as well as recommendations for fluoxetine and topiramate in BN and lisdexamfetamine and topiramate in BED. We majorly agree with these recommendations on the basis of the state of available literature. In addition, we see promise in, though at present do not have sufficient evidence to recommend novel agents aiming to treat EDs, including solriamfetol and semaglutide for BED, as well as psilocybin for AN.

The overall lack of innovation in ED pharmacotherapy is possibly the result of, and further compounded by, a persistent funding gap, with research investment failing to align with the severity and public health burden of EDs. Future research efforts may entail well-powered, placebo-controlled trials that investigate novel pharmacological agents, address the heterogeneity of EDs, and incorporate diverse participant populations to ensure treatment efficacy across different demographic groups.

Supplementary Information

Below is the link to the electronic supplementary material.

Funding

The authors declared that no funds, grants, or other support were received with respect to the research or authorship of this manuscript. Funding for open access publication of this article was provided by the University of California Libraries through a transformative agreement with the publisher.

Declarations

Conflict of Interest

The authors declared no potential competing interests with respect to the research, authorship, and/or publication of this article.

Availability of Data and Material

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

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Author Contributions

Waguih William IsHak, Drew Hirsch, Jace Reed, and Rebecca Hedrick contributed to the conceptualization and methodology of the article. The literature search and formal analysis were performed by Drew Hirsch, Jace Reed, Aasim Naqvi, Ashley Ngor, Lauren Dugan, Kelly Costa, Rolando Sceptre Ganasi, and Kyla Truman. The first draft of the manuscript was written by Drew Hirsch, Waguih William IsHak, Jace Reed, and Rolando Sceptre Ganasi. All authors critically edited and revised the work. All authors read and approved the final manuscript.