Disruptive Mood Dysregulation Disorder and Its Association with Treatment Trajectories and Outcomes in Youth with Attention-Deficit/Hyperactivity Disorder and Internalizing Disorders
Restricted accessResearch articleFirst published online 2026
Disruptive Mood Dysregulation Disorder and Its Association with Treatment Trajectories and Outcomes in Youth with Attention-Deficit/Hyperactivity Disorder and Internalizing Disorders
Disruptive mood dysregulation disorder (DMDD), along with other internalizing disorders, is associated with greater impairment in youth with attention-deficit/hyperactivity disorder (ADHD). However, it remains unclear whether DMDD is associated with differences in treatment course and outcomes among youth with ADHD and comorbid internalizing disorders. Using real-world data, this study compared treatment patterns and clinical outcomes among youth with ADHD and internalizing disorders with and without comorbid DMDD.
Methods:
A retrospective cohort study analyzed electronic health records from the TriNetX U.S. Collaborative Network, including 340,225 youth aged 6–18 years with ADHD and at least one internalizing disorder (major depressive disorders or anxiety disorder), of whom 25,580 (7.5%) had comorbid DMDD. Outcomes included treatment patterns and clinical outcomes. Propensity score matching and Cox proportional hazards models adjusted for confounding were used to estimate relative risks (RR), adjusted hazard ratios (aHR), and 95% confidence intervals (CI) over 1 year.
Results:
Youth with ADHD, internalizing disorders, and DMDD exhibited greater psychiatric comorbidity and higher healthcare utilization than those without DMDD. They received more ADHD medications, with a marked shift toward nonstimulants (RR 1.73, 95% CI 1.69–1.77), and other psychotropic medications, including antidepressants, antipsychotics, and mood stabilizers (RR range 1.36–3.02). New central nervous system (CNS) stimulant prescriptions did not differ between youth with and without DMDD. Compared with nonstimulants, CNS stimulants were associated with lower risks of all adverse outcomes—including suicidal ideation/attempts, inpatient hospitalization, emergency visits, and subsequent antipsychotic or mood stabilizer initiation—in youth both with and without DMDD (aHR range 0.33–0.73).
Conclusions:
Comorbid DMDD adds clinical complexity among youth with ADHD and internalizing disorders, influencing treatment patterns toward nonstimulants and other psychotropics. Despite this shift, CNS stimulants were associated with the most favorable outcomes across cohorts.
AmanMG, BuksteinOG, GadowKD, et al.What does risperidone add to parent training and stimulant for severe aggression in child attention-deficit/hyperactivity disorder? J Am Acad Child Adolesc Psychiatry2014;53(1):47–60.e41; doi: 10.1016/j.jaac.2013.09.022
2.
ArmstrongD, LycettK, HiscockH, et al.Longitudinal associations between internalizing and externalizing comorbidities and functional outcomes for children with ADHD. Child Psychiatry Hum Dev2015;46(5):736–748; doi: 10.1007/s10578-014-0515-x
3.
AustinPC. A comparison of 12 algorithms for matching on the propensity score. Stat Med2014;33(6):1057–1069.
4.
AxelsonD. Taking disruptive mood dysregulation disorder out for a test drive. Am J Psychiatry2013;170(2):136–139.
5.
BarbaresiWJ, CampbellL, DiekrogerEA, et al.Society for developmental and behavioral pediatrics clinical practice guideline for the assessment and treatment of children and adolescents with complex attention-deficit/hyperactivity disorder. J Dev Behav Pediatr2020;41 Suppl 2S:S35–S57.
6.
BawejaR, BelinPJ, HumphreyHH, et al.The effectiveness and tolerability of central nervous system stimulants in school-age children with attention-deficit/hyperactivity disorder and disruptive mood dysregulation disorder across home and school. J Child Adolesc Psychopharmacol2016a;26(2):154–163; doi: 10.1089/cap.2015.0053
7.
BawejaR, MayesSD, HameedU, et al.Disruptive mood dysregulation disorder: Current insights. Neuropsychiatr Dis Treat2016b;12:2115–2124; doi: 10.2147/NDT.S100312
8.
BawejaR, SoutulloCA, WaxmonskyJG. Review of barriers and interventions to promote treatment engagement for pediatric attention deficit hyperactivity disorder care. World J Psychiatry2021a;11(12):1206–1227.
9.
BawejaR, WaschbuschDA, KongL, et al.Pediatric attention-deficit/hypearativity disorder and disruptive mood dysregulation disorder: Analyzing national treatment trends. J Pediatr2025a;279:114471.
10.
BawejaR, WaschbuschDA, PadillaFM, et al.Attention-Deficit/Hyperactivity disorder treatment patterns and association with clinical outcomes in adolescents and young adults with co-occurring attention-deficit/hyperactivity disorder and substance use disorder: A retrospective analysis. J Am Acad Child Adolesc Psychiatry2025b:S0890.
11.
BawejaR, WaschbuschDA, PelhamIWE, et al.The impact of persistent irritability on the medication treatment of paediatric attention deficit hyperactivity disorder. Front Psychiatry2021b;12:699687.
12.
BawejaR, WaxmonskyJG.Treatment Implications for ADHD Youth with Mood and Anxiety Comorbidity. Curr Treat Options Psych2018;5(1):73–97; doi: 10.1007/s40501-018-0135-3
13.
BawejaR, WaxmonskyJG. Updates in pharmacologic strategies for emotional dysregulation in attention deficit hyperactivity disorder. Child Adolesc Psychiatr Clin N Am2022;31(3):479–498.
14.
BenarousX, LahayeH, ConsoliA, et al.Prevalence and comorbidity rates of disruptive mood dysregulation disorder in epidemiological and clinical samples: Systematic review and meta-analysis. Eur Psychiatry2025;68(1):e11; doi: 10.1192/j.eurpsy.2024.1813
15.
BladerJC, PliszkaSR, KafantarisV, et al.Stepped treatment for attention-deficit/hyperactivity disorder and aggressive behavior: A randomized, controlled trial of adjunctive risperidone, divalproex sodium, or placebo after stimulant medication optimization. J Am Acad Child Adolesc Psychiatry2021;60(2):236–251.
16.
BreauxR, BawejaR, EadehH-M, et al.Systematic review and meta-analysis: Pharmacological and nonpharmacological interventions for persistent nonepisodic irritability. J Am Acad Child Adolesc Psychiatry2023;62(3):318–334; doi: 10.1016/j.jaac.2022.05.012
17.
ConnorDF, FindlingRL, KollinsSH, et al.Effects of guanfacine extended release on oppositional symptoms in children aged 6–12 years with attention-deficit hyperactivity disorder and oppositional symptoms. CNS Drugs2010;24(9):755–768.
18.
CorteseS, AdamoN, Del GiovaneC, et al.Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: A systematic review and network meta-analysis. Lancet Psychiatry2018;5(9):727–738; doi: 10.1016/S2215-0366(18)30269-4
19.
CuffeSP, VisserSN, HolbrookJR, et al.ADHD and psychiatric comorbidity: Functional outcomes in a school-based sample of children. J Atten Disord2020;24(9):1345–1354; doi: 10.1177/1087054715613437
20.
FaraoneSV, BanaschewskiT, CoghillD, et al.The world federation of ADHD international consensus statement: 208 evidence-based conclusions about the disorder. Neurosci Biobehav Rev2021;128:789–818.
21.
FindlingRL, McBurnettK, WhiteC, et al.Guanfacine extended release adjunctive to a psychostimulant in the treatment of comorbid oppositional symptoms in children and adolescents with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol2014;24(5):245–252.
22.
FindlingRL, ZhouX, GeorgeP, et al.Diagnostic trends and prescription patterns in disruptive mood dysregulation disorder and bipolar disorder. J Am Acad Child Adolesc Psychiatry2022;61(3):434–445.
23.
FroehlichTE, BrinkmanWB, PeughJL, et al.Pre-Existing comorbid emotional symptoms moderate short-term methylphenidate adverse effects in a randomized trial of children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol2020;30(3):137–147; doi: 10.1089/cap.2019.0125
24.
GellerD, DonnellyC, LopezF, et al.Atomoxetine treatment for pediatric patients with attention-deficit/hyperactivity disorder with comorbid anxiety disorder. J Am Acad Child Adolesc Psychiatry2007;46(9):1119–1127; doi: 10.1097/chi.0b013e3180ca8385
25.
Geronazzo-AlmanL, GuffantiG, EisenbergR, et al.Comorbidity classes and associated impairment, demographics and 9/11-exposures in 8,236 children and adolescents. J Psychiatr Res2018;96:171–177; doi: 10.1016/j.jpsychires.2017.10.012
26.
HarstadE, ShultsJ, BarbaresiW, et al.α2-adrenergic agonists or stimulants for preschool-age children with attention-deficit/hyperactivity disorder. JAMA2021;325(20):2067–2075.
27.
KratochvilCJ, NewcornJH, ArnoldLE, et al.Atomoxetine alone or combined with fluoxetine for treating ADHD with comorbid depressive or anxiety symptoms. J Am Acad Child Adolesc Psychiatry2005;44(9):915–924; doi: 10.1097/01.chi.0000169012.81536.38
28.
LarsonK, RussSA, KahnRS, et al.Patterns of comorbidity, functioning, and service use for US children with ADHD, 2007. Pediatrics2011;127(3):462–470; doi: 10.1542/peds.2010-0165
29.
NewcornJH, HussM, ConnorDF, et al.Efficacy of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder. J Dev Behav Pediatr2020;41(7):565–570.
30.
NewcornJH, KratochvilCJ, AllenAJ, et al.; Atomoxetine/Methylphenidate Comparative Study Group. Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: Acute comparison and differential response. Am J Psychiatry2008;165(6):721–730.
31.
NjardvikU, WergelandGJ, RiiseEN, et al.Psychiatric comorbidity in children and adolescents with ADHD: A systematic review and meta-analysis. Clin Psychol Rev2025;118:102571; doi: 10.1016/j.cpr.2025.102571
32.
OlivaHNP, PrudenteTP, MayersonTF, et al.Safety of stimulants across patient populations: A meta-analysis. JAMA Netw Open2025;8(5):e259492-e259492; doi: 10.1001/jamanetworkopen.2025.9492
33.
PliszkaS, AACAP Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry2007;46(7):894–921.
34.
PozziM, CarnovaleC, MazharF, et al.Adverse drug reactions related to mood and emotion in pediatric patients treated for attention deficit/hyperactivity disorder: A comparative analysis of the us food and drug administration adverse event reporting system database. J Clin Psychopharmacol2019;39(4):386–392; doi: 10.1097/jcp.0000000000001058
35.
PozziM, CarnovaleC, PeetersGGAM, et al.Adverse drug events related to mood and emotion in paediatric patients treated for ADHD: A meta-analysis. J Affect Disord2018;238:161–178.
36.
SolmiM, FornaroM, OstinelliEG, et al.Safety of 80 antidepressants, antipsychotics, anti-attention-deficit/hyperactivity medications and mood stabilizers in children and adolescents with psychiatric disorders: A large scale systematic meta-review of 78 adverse effects. World Psychiatry2020;19(2):214–232; doi: 10.1002/wps.20765
37.
StrawnJR, ComptonSN, RobertsonB, et al.Extended release guanfacine in pediatric anxiety disorders: A pilot, randomized, placebo-controlled trial. J Child Adolesc Psychopharmacol2017;27(1):29–37.
38.
StuckelmanZD, MulqueenJM, Ferracioli-OdaE, et al.Risk of Irritability With Psychostimulant Treatment in Children With ADHD: A Meta-Analysis. J Clin Psychiatry2017;78(6):e648–e655; doi: 10.4088/JCP.15r10601
39.
SurmanCBH, WalshDM. Do ADHD treatments improve executive behavior beyond core ADHD Symptoms in Adults? Evidence From Systematic Analysis of Clinical Trials. J Clin Pharmacol2023;63(6):640–653; doi: 10.1002/jcph.2209
40.
TaipaleH, BergströmJ, GèmesK, et al.Attention-deficit/hyperactivity disorder medications and work disability and mental health outcomes. JAMA Netw Open2024;7(3):e242859.
41.
TowbinK, Vidal-RibasP, BrotmanMA, et al.A double-blind randomized placebo-controlled trial of citalopram adjunctive to stimulant medication in youth with chronic severe irritability. J Am Acad Child Adolesc Psychiatry2020;59(3):350–361; doi: 10.1016/j.jaac.2019.05.015
42.
UpshawBM, SpencerSD, PinciottiCM, et al.ADHD in youth with major depressive disorder in the texas youth depression and suicide research network (TX-YDSRN): Clinical correlates and moderators. J Atten Disord2025;29(13):1231–1246; doi: 10.1177/10870547251353392
43.
WangS, StewartTM, OzenI, et al.Rates of depression in children and adolescents with ADHD: A systematic review and meta-analysis. J Atten Disord2025;29(11):924–952; doi: 10.1177/10870547251341597
44.
WaxmonskyJG, BawejaR, BansalPS, et al.A review of the evidence base for psychosocial interventions for the treatment of emotion dysregulation in children and adolescents. Child Adolesc Psychiatr Clin N Am2021;30(3):573–594.
45.
WongICK, BanaschewskiT, BuitelaarJ, et al.; European ADHD Guidelines Group. Emerging challenges in pharmacotherapy research on attention-deficit hyperactivity disorder-outcome measures beyond symptom control and clinical trials. Lancet Psychiatry2019;6(6):528–537; doi: 10.1016/s2215-0366(19)30096-3
46.
ZhangL, ZhuN, SjölanderA, et al.ADHD drug treatment and risk of suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality: Emulation of target trials. Bmj2025;390:e083658; doi: 10.1136/bmj-2024-083658
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
