Pharmacological interventions for emotional dysregulation in ADHD: a meta-analysis stratified by sex and ADHD subtypes

Abstract Background Emotional dysregulation (ED) is increasingly recognized as a clinically significant and functionally impairing dimension of Attention-Deficit/Hyperactivity Disorder (ADHD), particularly in individuals with the combined presentation and in females (Beheshti et al., BMC Pscyhiatry 20:120,2020, Shaw et al., Am J Psychiat 171:276-293, 2014, Karalunas et al., J Child Psychol Psychiatry 64:55-65,2023). Despite this recognition, pharmacological strategies specifically targeting ED remain underexplored (Caye et al., Lancet Psychiatry 8:7956-810,2021, Krieger et al., J Child Adolesc Psychopharmacol 29:186-194,2019). Objective To synthesize and evaluate the efficacy of pharmacological treatments for emotional dysregulation in ADHD, with stratification by sex and ADHD subtype. Methods This meta-analysis included 20 peer-reviewed studies published between 2010 and 2025 that utilized validated instruments to assess ED (e.g., CBCL-DP (Grizenko et al., J Am Acad Child Adolesc Psychiatry 56:984-992,2017), DERS (Beheshti et al., BMC Pscyhiatry 20:120,2020), BRIEF(Mahone et al., J Atten Disord 20:673-684,2016, Musser et al., J Abnorm Child Psychol 48:L683-695,2020)). The studies evaluated the effects of both stimulant medications (e.g., methylphenidate, lisdexamfetamine) and non-stimulant agents (e.g., atomoxetine, guanfacine) (Krieger et al., J Child Adolesc Psychopharmacol 29:186-194,2019, Grizenko et al., J Am Acad Child Adolesc Psychiatry 56:984-992,2017, Waltereit et al., Front Child Adolesc Psychiatry 2:1547672,2025). Data were extracted on age, medication class, stratification variables, and pre-/post-treatment ED outcomes. Results Most stimulant treatments were associated with significant reductions in ED, particularly among individuals with the combined ADHD subtype (Caye et al., Lancet Psychiatry 8:7956-810,2021, Grizenko et al., J Am Acad Child Adolesc Psychiatry 56:984-992,2017, Posner et al., Biol Psychiatry: Cogn Neurosci Neuroimaging 6:142-151,2021). Guanfacine and atomoxetine demonstrated moderate efficacy, especially in individuals with the inattentive subtype and in females (Krieger et al., J Child Adolesc Psychopharmacol 29:186-194,2019, Waltereit et al., Front Child Adolesc Psychiatry 2:1547672,2025, Schmid et al., J Child Psychol Psychiatry 66:512-523,2025). Several studies reported sex differences in both baseline ED severity and treatment response (Beheshti et al., BMC Pscyhiatry 20:120,2020, Karalunas et al., J Child Psychol Psychiatry 64:55-65,2023, Reinhardt et al., BMC Psychiatry 24:153,2024, Wigal et al., J Atten Disord 29:706-723,2025). Conclusion Pharmacological treatment significantly reduces emotional dysregulation in ADHD, with central stimulants demonstrating the strongest efficacy. Clinicians should incorporate sex and ADHD subtype-specific stratifications to optimize personalized pharmacological strategies and improve patient outcomes (Beheshti et al., BMC Pscyhiatry 20:120,2020, Caye et al., Lancet Psychiatry 8:7956-810,2021, Karalunas et al., J Child Psychol Psychiatry 64:55-65,2023). This review was conducted and reported in accordance with the PRISMA 2020 guidelines for systematic reviews and meta-analyses.