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

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.

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. 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. 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.

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.

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 Summary of clinical trials for other eating disorders (2010–2025) Baclofen 10 mg/three times daily 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 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 ]. 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.

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.

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.

Below is the link to the electronic supplementary material. Supplementary file1 (PDF 346 KB) Supplementary file1 (PDF 346 KB)