The study, led by Elena Koning of Dalhousie University and Nova Scotia Health together with colleagues from institutions including Vrije Universiteit Amsterdam and Deakin University, pooled data from 47 randomized controlled trials encompassing 57 treatment comparisons and 3,018 adults. Unlike earlier syntheses that focused narrowly on CBT, the team deliberately widened the aperture to include non-CBT guided psychotherapies such as dialectical behavioral therapy, interpersonal psychotherapy, and emotion-focused therapy. The goal was to determine, for the first time, the controlled effect of psychotherapy as a class against comparison conditions, which were primarily waitlist controls or care-as-usual arrangements.

The headline result is striking. Across all eating disorder diagnoses combined, psychotherapy produced a large overall effect on eating disorder psychopathology, with a standardized effect size of Hedges’ g equal to 0.96 and a 95 percent confidence interval running from 0.79 to 1.14. In practical terms, an effect of this magnitude means the average treated patient fared better than roughly 83 percent of untreated or usual-care controls, a difference that places eating disorder psychotherapy among the more effective interventions in all of mental health care. The effects were remarkably consistent across diagnostic categories, with bulimia nervosa showing an effect size of 0.97 and binge-eating disorder an almost identical 0.95.

Perhaps the most consequential finding for the field is what the analysis did not find: any significant difference between CBT and its non-CBT rivals. Dialectical behavioral therapy, interpersonal psychotherapy, emotion-focused therapy, and other guided approaches performed on par with the presumed gold standard. This challenges a long-standing assumption embedded in treatment guidelines and insurance policies around the world, namely that CBT should be the default first-line option while other therapies serve as fallbacks. The authors suggest that the common therapeutic ingredients shared across these modalities, rather than any single theoretical framework, may be driving much of the benefit.

The binary outcome data tell the story in raw clinical terms. After treatment, 37 percent of patients receiving psychotherapy had achieved abstinence from binge eating, compared with just 18 percent of those in control conditions, yielding a relative risk of 3.79 with a confidence interval of 2.98 to 4.83. In other words, treated adults were nearly four times as likely to stop binge eating as their untreated counterparts. Secondary outcomes reinforced the pattern, with statistically significant effects on binge eating frequency, vomiting episodes, and concerns about shape, weight, and eating, the core cognitive symptoms that maintain these disorders and predict relapse.

Methodologically, the analysis was conducted with considerable statistical sophistication. The researchers used Hedges’ g for continuous outcomes and relative risks for binary outcomes, and they ran their models with the metapsyTools R package, an open-source platform designed for handling the correlated and hierarchical structure of multi-arm psychotherapy trials. This matters because psychotherapy trials frequently include multiple treatment arms and multiple outcome measures per study, and naive pooling can distort effect estimates. By modeling these dependencies explicitly, the team reduced the risk of overstating both the size and the precision of their findings.

But the analysis also delivered a cautionary note that the authors do not shy away from. When the team examined the subset of studies judged to have a low risk of bias, the effects were attenuated, meaning the most methodologically rigorous trials produced smaller benefits than the literature as a whole. This is a familiar pattern in psychotherapy research, where blinding is difficult, expectation effects are powerful, and waitlist comparisons can inflate apparent treatment effects. The finding does not overturn the conclusion that psychotherapy works, but it tempers the enthusiasm and suggests the true effect likely sits somewhere below the headline estimate.

Even more sobering is the recovery gap that persists despite the large average effects. If only 37 percent of treated patients achieve binge-eating abstinence against 18 percent of controls, then roughly two-thirds of adults receiving first-line psychotherapy do not reach that benchmark of clinical remission. The authors are explicit on this point: psychotherapy should remain the first-line treatment for eating disorders, but there remains a pressing need for improved therapeutic approaches. The number needed to treat implied by these figures, while respectable by mental health standards, underscores that current therapies are a starting point rather than a solution.

The implications ripple outward in several directions. For clinicians, the equivalence finding means that patient preference, therapist training, and practical considerations such as format and duration can legitimately guide the choice among evidence-based psychotherapies, rather than a rigid CBT-first mandate. For guideline developers, the results argue for broadening first-line recommendations to include non-CBT modalities supported by randomized trial evidence. For researchers, the persistent remission gap and the risk-of-bias attenuation together define the field’s next frontier: developing interventions that work for the many patients whom current approaches leave behind, and designing trials rigorous enough to measure honestly whether they do.

Published open access and citable under a permanent DOI, the analysis arrives at a moment when eating disorders are receiving unprecedented public attention and demand for treatment continues to outpace service capacity. Its message to patients and families is genuinely hopeful: guided psychotherapy, in several distinct forms, produces large and measurable reductions in the symptoms that make these illnesses so destructive. Its message to the research community is equally clear. The era of asking whether psychotherapy works for eating disorders in adults is essentially over; the era of asking how to make it work for everyone has begun.

Subject of Research: Controlled effects of CBT and non-CBT psychotherapy for eating disorders in adults

Article Title: The effects of eating disorder psychotherapy in adults: a meta-analysis of randomized controlled trials

Article References: Koning, E., Trappenberg, N., Harris, A., Brown, V., Mittertreiner, E. J., Sheppard, S., Sprenger, A. A., Harrer, M., Cuijpers, P., Linardon, J., & Keshen, A. (2026). The effects of eating disorder psychotherapy in adults: a meta-analysis of randomized controlled trials. Journal of Eating Disorders. https://doi.org/10.1186/s40337-026-01794-5

Image Credits: AI Generated

DOI: 10.1186/s40337-026-01794-5

Keywords: eating disorders, psychotherapy, cognitive behavioral therapy, meta-analysis, bulimia nervosa, binge-eating disorder, dialectical behavioral therapy, interpersonal psychotherapy, randomized controlled trials, remission rates, mental health, clinical psychology

Hairy cell leukemia is an uncommon malignancy of hematopoietic stem cells, named for the fine, hair-like projections that cover the surface of the malignant cells. It predominantly affects men and is driven in nearly all cases by a single acquired mutation, BRAF V600E, which was identified more than a decade ago and has since become both a diagnostic marker and a therapeutic target. The disease has a remarkable treatment history: described first in 1923, it was initially managed with splenectomy, then advanced through interferon and the purine analog pentostatin before cladribine, a nucleoside analog that is toxic to lymphocytes, became the backbone of therapy. More recently, combinations of cladribine with the monoclonal antibody rituximab have pushed remission rates even higher, and BRAF inhibitors such as vemurafenib have shown excellent results in refractory cases. Yet for all these advances, the standard cladribine schedule, a continuous infusion given on five to seven consecutive days, has remained essentially unchanged for two decades.

That constancy has persisted despite a persistent problem: toxicity. Cladribine profoundly depletes normal white blood cells, particularly neutrophils, leaving patients vulnerable to serious bacterial infections. Many require hospitalization, intravenous antibiotics, growth factor support, and blood product transfusions during the weeks following treatment. The concern became acute roughly fifteen years ago when deaths occurred among patients receiving continuous cladribine infusions. This prompted a handful of investigators to ask whether the same drug, delivered as one weekly outpatient infusion instead of daily doses, might achieve comparable disease control with far less collateral damage. The idea has biological logic: cladribine is a long-acting drug that accumulates in lymphocytes, and stretching its delivery across weeks may moderate the depth and duration of immunosuppression without compromising the lethal effect on malignant cells. Prior studies comparing the two schedules, including two prospective randomized trials from European groups, produced mixed results, with some finding no significant difference in efficacy and others reporting fewer neutropenic and infectious complications with weekly dosing.

The new study, led by Jacqueline A. Turner and colleagues including William A. Robinson, adds substantially to this literature by combining treatment response data with long-term survival analysis and modern molecular monitoring. The researchers identified 36 treatment-naïve patients with hairy cell leukemia treated at their institution since 2002. Eighteen received intermittent cladribine, meaning one infusion per week for 5 to 7 weeks, while 18 received the standard continuous schedule of daily outpatient infusions over 5 to 7 days. The groups were broadly similar at baseline: 83.3 percent of patients in each group were male, and initial white blood cell counts, hemoglobin concentrations, and platelet counts were statistically indistinguishable. The median age at diagnosis differed notably, at 58 years in the weekly-dosing group versus 45 years in the continuous group, a disparity the authors acknowledge may reflect shifting referral patterns over the two-decade study window.

The efficacy results favored weekly dosing on every clinically meaningful measure tested. Beyond the difference in complete remission rates, 94.4 percent versus 61.1 percent, no patient in the weekly group experienced progressive disease, while 38.9 percent of the continuous-infusion group did. Kaplan-Meier analysis showed no difference in overall survival between the groups, a finding the authors attribute to the effectiveness of salvage therapies at relapse, but progression-free survival differed profoundly, with a p-value below 0.0001 by log-rank testing. Hospitalizations during treatment induction were less frequent with weekly dosing, affecting 4 of 18 patients compared with 6 of 18, and among three patients in the study who had relapsed after continuous cladribine and were later re-challenged with the weekly schedule, all achieved complete responses, with two remaining in remission for years and none requiring hospitalization during the weekly regimen, in contrast to hospitalizations and neutropenic fevers that had complicated their original continuous-infusion treatment.

Toxicity data painted a more nuanced picture. Neutropenia was nearly universal in both groups, affecting 88.9 percent of weekly-dosing patients and 92.9 percent of continuous-infusion patients with recorded data, and neutropenic fever occurred in roughly 43 to 44 percent of both groups. Antibiotic use was identical at 50 percent, and the proportion of patients requiring growth factor support or blood product transfusions was also comparable. This raises an important interpretive question, because the weekly group was far more likely to have received rituximab after cladribine, 72.2 percent versus 27.2 percent, a chemoimmunotherapy addition that has itself been shown to deepen remissions and extend survival. The authors are candid about this limitation, noting that the non-randomized design and the imbalance in rituximab exposure may have contributed to the observed differences and preclude definitive conclusions about which element of the regimen drives the benefit.

The study also offers a window into the future of disease monitoring in hairy cell leukemia. In a subset of more recently treated patients, the team used quantitative polymerase chain reaction on peripheral blood samples to track the frequency of the mutant BRAF V600E allele, essentially using the driver mutation itself as a measurable residual disease marker. At five years after treatment, all tested patients in both groups had undetectably low levels of the mutant allele, and the decline in mutant allele burden correlated closely with clinical remission. Because the assay requires only a blood draw, the authors argue it could serve as a less invasive alternative to the repeated bone marrow biopsies traditionally used to assess remission depth, and they recommend that serial BRAF mutant allele frequency testing be incorporated into routine care. The feasibility of monitoring relapse through a simple blood test is particularly attractive in a disease whose treatment is most effective when started early.

The rarity of hairy cell leukemia complicates the path forward. With only a few thousand new cases diagnosed annually in the United States, prospective randomized trials comparing the two schedules are difficult to mount and slow to accrue, which helps explain why the question has lingered for decades with only mixed and limited answers. The two previously conducted randomized trials, from the Polish Adult Leukemia Group and the Swiss Group for Clinical Cancer Research, found no significant efficacy differences, while earlier Italian work by Lauria and colleagues and by Zinzani and colleagues reported that weekly administration reduced infectious complications. The Colorado experience, with its extended follow-up and favorable progression-free survival signal, tilts the accumulated evidence somewhat further toward the weekly schedule, though the authors concede that confirmation in larger, prospective, ideally multi-institutional cohorts would be valuable and have committed to continuing to expand and update their own series.

For patients, the practical implications are appealing regardless of which component of the regimen proves decisive. A once-weekly outpatient infusion eliminates the logistical burden of consecutive daily hospital visits, and the reduced hospitalization rate translates into fewer exposures to drug-resistant hospital pathogens for an already immunocompromised population. Because most hairy cell leukemia patients are older and carry comorbidities, the authors emphasize that an ideal regimen must be both effective and low-risk across short- and long-term horizons, criteria they argue weekly cladribine followed by rituximab appears to meet. Their conclusion is measured but hopeful: the weekly schedule represents a feasible strategy supported by institutional experience, and while randomized validation would be ideal, the totality of the data, higher complete remission rates, superior progression-free survival, comparable overall survival and toxicity, and fewer hospitalizations, suggests a genuine clinical benefit that the field should not ignore.

The study arrives at a moment when the treatment of hairy cell leukemia is already undergoing a molecular renaissance, driven by the discovery that a single point mutation powers the disease and by the growing clinical repertoire of BRAF inhibitors and antibody combinations. Against that backdrop, the Colorado findings are a reminder that sometimes meaningful progress in oncology comes not from new molecules but from new ways of using old ones. Cladribine has been a mainstay of hairy cell leukemia therapy since the early 1990s, and if simply rearranging its administration calendar can keep more patients in durable remission with fewer trips to the hospital, the change would cost essentially nothing to implement. Whether weekly cladribine followed by rituximab formally becomes the new standard will depend on the larger studies the authors call for, but for a disease that has long been a treatment success story, this work proposes a way to make the story even better.