This article presents the protocol for an open-label clinical trial examining the effectiveness of atomoxetine augmentation in adolescents with nonsuicidal self-injury (NSSI) and attention problems and reports preliminary findings from the initial group of participants.
Methods:
Adolescents (n = 27) aged 13–18 years who met the criteria for NSSI according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and had either full or subclinical attention-deficit/hyperactivity disorder (ADHD) were recruited. All participants had not received ADHD medication for at least 4 weeks prior to enrollment. Psychiatric diagnoses were confirmed using the Kiddie Schedule for Affective Disorders and Schizophrenia. After 12 weeks of adjunctive atomoxetine treatment, NSSI severity (primary outcome) was measured using the Inventory of Statements About Self-Injury. Secondary outcomes included the Children’s Depression Rating Scale (CDRS), the Children’s Depression Inventory (CDI), the Screen for Child Anxiety Related Emotional Disorders (SCARED), and DuPaul’s ADHD Rating Scale (ARS). Additional assessments targeting factors related to NSSI included demographic characteristics, childhood adversity, personality functioning, continuous performance task, and functional near-infrared spectroscopy.
Results:
Twenty-three participants (22 female, 1 male) completed the trial (mean final dose: 58.3 ± 13.7 mg), while four discontinued (two voluntarily, two due to adverse events). Significant improvements were observed in CDRS (p < 0.001), CDI (p = 0.031), and NSSI severity (p = 0.007). In the ADHD group, significant improvements were observed in CDRS (p = 0.017) and NSSI severity (p = 0.034), with a trend toward improvement in CDI (p = 0.058). The subclinical ADHD group showed significant improvement in CDRS (p = 0.006), with a trend toward improvement in NSSI severity (p = 0.083).
Conclusion:
Atomoxetine augmentation may reduce NSSI severity in adolescents with attention problems, particularly in those with comorbid ADHD, warranting further investigation in larger controlled trials.
AdlerLA, LiebowitzM, KronenbergerW, et al.Atomoxetine treatment in adults with attention-deficit/hyperactivity disorder and comorbid social anxiety disorder. Depress Anxiety, 2009; 26(3):212–221; doi: 10.1002/da.20549
2.
BangsME, WietechaLA, WangS, et al.Meta-analysis of suicide-related behavior or ideation in child, adolescent, and adult patients treated with atomoxetine. J Child Adolesc Psychopharmacol, 2014; 24(8):426–434; doi: 10.1089/cap.2014.0005
3.
BenderDS, SkodolAE, FirstMB, et al.Structured Clinical Interview for the DSM-5® Alternative Model for Personality Disorders (SCID-5-AMPD) MODULE I LEVEL of Personality Functioning Scale. APPI: Washington, DC; 2018.
4.
BishopJR, ZhouC, GaedigkA, et al.Dopamine transporter and CYP2D6 gene relationships with attention-deficit/hyperactivity disorder treatment response in the methylphenidate and atomoxetine crossover study. J Child Adolesc Psychopharmacol, 2024; 34(10):458–469.
5.
BrownN, McLaffertyM, O’NeillSM, et al.The mediating roles of mental health and substance use on suicidal behavior among undergraduate students with ADHD. J Atten Disord, 2022; 26(11):1437–1451; doi: 10.1177/10870547221075844
6.
ChangZ, QuinnPD, O’ReillyL, et al.Medication for attention-deficit/hyperactivity disorder and risk for suicide attempts. Biol Psychiatry, 2020; 88(6):452–458; doi: 10.1016/j.biopsych.2019.12.003
7.
ChengF, ShiL, XieH, et al.A study of the interactive mediating effect of ADHD and NSSI caused by co-disease mechanisms in males and females. PeerJ, 2024; 12:e16895; doi: 10.7717/peerj.16895
8.
ChoSC, LeeYS. Development of the Korean form of the Kovacs’ Children’s Depression Inventory. J Korean Neuropsychiatr Assoc, 1990; 29(5):943–956.
9.
DavisKL, PankseppJ, NormansellL. The affective neuroscience personality scales: Normative data and implications. Neuropsychoanalysis, 2003; 5(1):57–69; doi: 10.1080/15294145.2003.10773410
10.
Di SalvoG, PerottiC, FilippoL, et al.Assessing suicidality in adult ADHD patients: Prevalence and related factors. Ann Gen Psychiatry, 2024; 23(1):42; doi: 10.1186/s12991-024-00528-8
11.
DuPaul GJ, Power TJ, Anastopoulos AD, et al. ADHD Rating Scale—IV: Checklists, norms, and clinical interpretation. The Guilford Press: New York, NY; 1998.
12.
EggartV, CordierS, HasanA, et al.Psychotropic drugs for the treatment of non-suicidal self-injury in children and adolescents: A systematic review and meta-analysis. Eur Arch Psychiatry Clin Neurosci, 2022; 272(8):1559–1568; doi: 10.1007/s00406-022-01385-w
13.
ErskineHE, NormanRE, FerrariAJ, et al.Long-Term outcomes of attention-deficit/hyperactivity disorder and conduct disorder: A systematic review and meta-analysis. J Am Acad Child Adolesc Psychiatry, 2016; 55(10):841–850; doi: 10.1016/j.jaac.2016.06.016
14.
EvansMK, GroveJL, PatelTA, et al.Attention-deficit/hyperactivity disorder and nonsuicidal self-injury among veterans with complex psychiatric presentations. Psychiatry Res, 2022; 314:114618; doi: 10.1016/j.psychres.2022.114618
15.
FuD, WuDD, GuoHL, et al.The mechanism, clinical efficacy, safety, and dosage regimen of atomoxetine for ADHD therapy in children: A narrative review. Front Psychiatry, 2021; 12:780921; doi: 10.3389/fpsyt.2021.780921
16.
FurmanL. What is attention-deficit hyperactivity disorder (ADHD)? J Child Neurol, 2005; 20(12):994–1002; doi: 10.1177/08830738050200121301
17.
GaedigkA, SangkuhlK, Whirl-CarrilloM, et al.Prediction of CYP2D6 phenotype from genotype across world populations. Genet Med, 2017; 19(1):69–76.
18.
GarasP, BalazsJ. Long-term suicide risk of children and adolescents with attention deficit and hyperactivity disorder—A systematic review. Front Psychiatry, 2020; 11:557909; doi: 10.3389/fpsyt.2020.557909
19.
GiupponiG, GiordanoG, ManiscalcoI, et al.Suicide risk in attention-deficit/hyperactivity disorder. Psychiatr Danub, 2018; 30(1):2–10; doi: 10.24869/psyd.2018.2
20.
GrahamJ, BanaschewskiT, BuitelaarJ, et al.; European Guidelines Group. European guidelines on managing adverse effects of medication for ADHD. Eur Child Adolesc Psychiatry, 2011; 20(1):17–37; doi: 10.1007/s00787-010-0140-6
21.
HayesAF. PROCESS: A versatile computational tool for observed variable mediation, moderation, and conditional process modeling. 2012. Available from: https://www.processmacro.org/index.html [Last accessed: July5, 2025].
22.
IsakssonJ, RuchkinV, LindbladF. Unseen and stressed? Gender differences in parent and teacher ratings of ADHD symptoms and associations with perceived stress in children with ADHD. J Atten Disord, 2020; 24(11):1565–1569; doi: 10.1177/1087054716658381
23.
JeonJR, LeeEH, LeeSW, et al.The early trauma inventory self report-short form: Psychometric properties of the Korean version. Psychiatry Investig, 2012; 9(3):229–235.
24.
KhoodoruthMAS, OuanesS, KhanYS. A systematic review of the use of atomoxetine for management of comorbid anxiety disorders in children and adolescents with attention-deficit hyperactivity disorder. Res Dev Disabil, 2022; 128:104275; doi: 10.1016/j.ridd.2022.104275
25.
KimJH, ParkS, LeeYJ. Systematic review of suicidal behaviors related to methylphenidate and atomoxetine in patients with attention deficit hyperactivity disorder. J Korean Acad Child Adolesc Psychiatry, 2023; 34(2):125–132; doi: 10.5765/jkacap.220040
26.
KimKM, NamS, ChoiJW, et al.Psychometric properties and factor structures of the Korean version of Children’s Depression Rating Scale-Revised. J Child Adolesc Psychopharmacol, 2018; 28(4):285–292; doi: 10.1089/cap.2016.0183
27.
KimS, KimY, HurJW. Nonsuicidal self-injury among Korean young adults: A validation of the Korean version of the Inventory of Statements About Self-Injury. Psychiatry Investig, 2019; 16(4):270–278; doi: 10.30773/pi.2019.01.23
28.
KimYS, SoYK, NohJS, et al.Normative data on the Korean ADHD Rating Scales (K-ARS) for parents and teacher. J Korean Neuropsychiatr Assoc, 2003; 42(3):352–359.
29.
KirovaAM, KelbermanC, StorchB, et al.Are subsyndromal manifestations of attention deficit hyperactivity disorder morbid in children? A systematic qualitative review of the literature with meta-analysis. Psychiatry Res, 2019; 274:75–90; doi: 10.1016/j.psychres.2019.02.003
30.
KlonskyED, VictorSE, SafferBY. Nonsuicidal self-injury: What we know, and what we need to know. Can J Psychiatry, 2014; 59(11):565–568; doi: 10.1177/070674371405901101
31.
LedbetterM. Atomoxetine: A novel treatment for child and adult ADHD. Neuropsychiatr Dis Treat, 2006; 2(4):455–466; doi: 10.2147/nedt.2006.2.4.455
32.
LeeJ, KimSJ, KimD, et al.Computerized version of the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children (KSADS-COMP): Development and validation of the Korean clinician-administered version. Psychiatry Investig, 2023; 20(2):174–179; doi: 10.30773/pi.2022.0273
33.
LindenS, BussingR, KubilisP, et al.Risk of suicidal events with atomoxetine compared to stimulant treatment: A cohort study. Pediatrics, 2016; 137(5):e20153199; doi: 10.1542/peds.2015-3199
34.
LiuWJ, MaoHJ, HuLL, et al.Attention-deficit/hyperactivity disorder medication and risk of suicide attempt: A meta-analysis of observational studies. Pharmacoepidemiol Drug Saf, 2020; 29(11):1364–1372; doi: 10.1002/pds.5110
35.
MaiTA, ScheeringaMS. Caregiver and child agreement on traumatic events, PTSD, internalizing, externalizing, and ADHD problems in a child welfare population. J Public Child Welf, 2021; 15(2):251–274; doi: 10.1080/15548732.2019.1701612
36.
MartinJ. Why are females less likely to be diagnosed with ADHD in childhood than males? Lancet Psychiatry, 2024; 11(4):303–310; doi: 10.1016/S2215-0366(24)00010-5
37.
MichelsonD, AdlerL, SpencerT, et al.Atomoxetine in adults with ADHD: Two randomized, placebo-controlled studies. Biol Psychiatry, 2003; 53(2):112–120; doi: 10.1016/s0006-3223(02)01671-2
38.
MitchellRJ, HowlettS, EarlL, et al.Distribution of the 3′VNTR polymorphism in the human dopamine transporter gene in world populations. Hum Biol, 2000; 72(2):295–304.
39.
Morein-ZamirS, DoddsC, van HarteveltTJ, et al.Hypoactivation in right inferior frontal cortex is specifically associated with motor response inhibition in adult ADHD. Hum Brain Mapp, 2014; 35(10):5141–5152; doi: 10.1002/hbm.22539
40.
OjalaO, Kuja-HalkolaR, BjurebergJ, et al.Associations of impulsivity, hyperactivity, and inattention with nonsuicidal self-injury and suicidal behavior: Longitudinal cohort study following children at risk for neurodevelopmental disorders into mid-adolescence. BMC Psychiatry, 2022; 22(1):679; doi: 10.1186/s12888-022-04311-5
41.
OzdemirE, KaramanMG, YurteriN, et al.A case of suicide attempt with long-acting methylphenidate (Concerta). Atten Defic Hyperact Disord, 2010; 2(3):103–105; doi: 10.1007/s12402-010-0026-y
42.
Pereira-SanchezV, FrancoAR, VieiraD, et al.Systematic review: Medication effects on brain intrinsic functional connectivity in patients with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry, 2021; 60(2):222–235; doi: 10.1016/j.jaac.2020.10.013
43.
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 Psychopharmacol, 2019; 39(4):386–392; doi: 10.1097/JCP.0000000000001058
44.
RegierDA, KuhlEA, KupferDJ. The DSM-5: Classification and criteria changes. World Psychiatry, 2013; 12(2):92–98; doi: 10.1002/wps.20050
45.
ShakerNM, OsamaY, BarakatDH, et al.Atomoxetine in attention-deficit/hyperactivity disorder in children with and without comorbid mood disorders. J Child Adolesc Psychopharmacol, 2021; 31(5):332–341; doi: 10.1089/cap.2020.0178
46.
ShinJ, KimKM, LeeKH, et al.Psychometric properties and factor structure of the Korean version of the screen for Child Anxiety Related Emotional Disorders (SCARED). BMC Psychiatry, 2020; 20(1):89; doi: 10.1186/s12888-020-02505-3
47.
SteinhoffA, RibeaudD, KupferschmidS, et al.Self-injury from early adolescence to early adulthood: Age-related course, recurrence, and services use in males and females from the community. Eur Child Adolesc Psychiatry, 2021; 30(6):937–951; doi: 10.1007/s00787-020-01573-w
48.
TaylorPJ, JomarK, DhingraK, et al.A meta-analysis of the prevalence of different functions of non-suicidal self-injury. J Affect Disord, 2018; 227:759–769; doi: 10.1016/j.jad.2017.11.073
49.
VasiliadisHM, RochetteL, MassambaV, et al.Association between stimulant and non-stimulant ADHD medications and completed suicide in adolescents and adults: A population-based nested case-control study. Psychiatry Res, 2025; 344:116309; doi: 10.1016/j.psychres.2024.116309
50.
WangYJ, LiX, NgCH, et al.Risk factors for non-suicidal self-injury (NSSI) in adolescents: A meta-analysis. eClinicalMedicine, 2022; 46:101350; doi: 10.1016/j.eclinm.2022.101350
51.
WeissenbergerS, PtacekR, Klicperova-BakerM, et al.ADHD, lifestyles and comorbidities: A call for an holistic perspective—From medical to societal intervening factors. Front Psychol, 2017; 8:454; doi: 10.3389/fpsyg.2017.00454
52.
WiklundJ, YuW, TuckerR, et al.ADHD, impulsivity and entrepreneurship. J Bus Venturing, 2017; 32(6):627–656; doi: 10.1016/j.jbusvent.2017.07.002
53.
WuCS, ShangCY, LinHY, et al.Differential treatment effects of methylphenidate and atomoxetine on executive functions in children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol, 2021; 31(3):187–196; doi: 10.1089/cap.2020.0146
54.
YangCM, ShinJ, KimJI, et al.Classifying children with ADHD based on prefrontal functional near-infrared spectroscopy using machine learning. Clin Psychopharmacol Neurosci, 2023; 21(4):693–700; doi: 10.9758/cpn.22.1025
55.
YooHIK, LeeJS, KangSH, et al.Standardization of the comprehensive attention test for the Korean children and adolescents. J Korean Acad Child Adolesc Psychiatry, 2009; 20(2):68–75.
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