Dasotraline Hydrochloride

Currently, placebo-controlled clinical trials report mean change and effect sizes, which masks information about heterogeneity of treatment effects (HTE). Here, we present a novel method to estimate HTE and evaluate the null hypothesis (H₀) that a drug has equal benefit for all participants (HTE = 0). We developed a measure termed 'estimated heterogeneity of treatment effect' or eHTE, which compares the distributions between study arms to test for heterogeneity in drug response - rather than testing if any specific covariate impacts response. First, we used simulations to test fidelity, sensitivity and power of eHTE to detect heterogeneity. We found that eHTE accurately estimated heterogeneity in many cases (though under-estimated heterogeneity at times) and could detect realistic heterogeneity in trials around N = 200. Then, the approach was tested across numerous large placebo-controlled clinical trials. In contrast with variance-based methods which have not identified heterogeneity in psychiatric trials, reproducible instances of treatment heterogeneity were found. For example, heterogeneous response was found in a trial of venlafaxine for depression (p_eHTE = 0.034), and two trials of dasotraline for binge eating disorder (Phase 2, p_eHTE = 0.002; Phase 3, 4 mg p_eHTE = 0.011; Phase 3, 6 mg p_eHTE = 0.003). Significant response heterogeneity was detected in other datasets as well, often despite no difference in variance between placebo and drug arms. The implications of eHTE as a clinical trial outcomes, independent of central tendency of the group, is considered and the importance of the eHTE method and results for drug developers, providers, and patients is discussed.

Binge eating disorder (BED) is a psychiatric diagnosis involving recurrent episodes of compulsive overeating followed by ensuing distress. Despite its significant impact on mental and physical health, pharmacological treatment options remain limited. We present the first network meta‐analysis synthetizing evidence on the efficacy, safety, and tolerability of pharmacological interventions for BED.

A systematic search across PubMed, Embase, Web of Science, Cochrane Library, PsycINFO, and LILACS was conducted to identify randomized controlled trials assessing pharmacological‐only interventions for adults with BED. Outcomes included reduction in binge‐eating episode frequency, changes from baseline in weight, BMI, and eating disorder scores, along with remission rates, medication discontinuation rates, and adverse events. The DerSimonian‐Laird random‐effects model was employed to estimate the overall effect size across studies. Heterogeneity was estimated using I2, Tau‐squared (τ2), and Cochrane's Q χ2 tests. Risk of bias was assessed using RoB2 Tool.

Among findings with high‐certainty evidence, topiramate showed the greatest efficacy for reducing binge‐eating episodes (mean difference [MD] = −1.72) and promoting remission (odds ratio [OR] = 3.99), followed by lisdexamfetamine (MD = −1.50; OR = 3.33) and dasotraline (MD = −0.97; OR = 1.97). Lisdexamfetamine had the highest odds of adverse events, including anxiety, insomnia, diarrhea, and headache. Most studies failed to use validated assessment instruments and inconsistently defined remission periods.

Topiramate, lisdexamfetamine, and dasotraline show significant potential in treating BED. However, the landscape of pharmacotherapy for BED lacks robust evidence and methodological standardization. Larger trials with expanded sample sizes and using validated scales are needed to guide clinical practice for this highly prevalent and damaging disorder.