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Cited by 154Attention Deficit Hyperactivity DisorderSchizophrenia research and treatmentChild and Adolescent Psychosocial and Emotional Development

Medication for attention-deficit/hyperactivity disorder and risk for depression: a nationwide longitudinal cohort study

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Chang, Zheng, D’Onofrio, Brian M., Quinn, Patrick D., Lichtenstein, Paul, Larsson, Henrik·2016·Biological Psychiatry
DOI 10.1016/j.biopsych.2016.02.018PMC PMC4995143
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Abstract

Background Attention-deficit/hyperactivity disorder (ADHD) is associated with high rates of psychiatric comorbidity, including depression. However, it is unclear whether ADHD medication increases or decreases the risk for depression.Methods We studied all individuals with a diagnosis of ADHD born between 1960 and 1998 in Sweden (N = 38,752). We obtained data for prescription of ADHD medication, diagnosis of depression and other psychiatric disorders, and sociodemographic factors from population-based registers. The association between ADHD medication and depression was estimated with Cox proportional hazards regression.Results After adjustment for sociodemographic and clinical confounders, ADHD medication was associated with a reduced long-term risk (i.e., 3 years later) for depression (hazard ratio = 0.58; 95% confidence interval, 0.51-0.67). The risk was lower for longer duration of ADHD medication. Also, ADHD medication was associated with reduced rates of concurrent depression; within-individual analysis suggested that occurrence of depression was 20% less common during periods when patients received ADHD medication compared with periods when they did not (hazard ratio = 0.80; 95% confidence interval, 0.70-0.92).Conclusions Our study suggests that ADHD medication does not increase the risk of later depression; rather, medication was associated with a reduced risk for subsequent and concurrent depression.

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  • Patients with ADHD, whether treated or not, are at increased risk for early death, suicide, and increased psychiatric comorbidity, particularly substance use disorders.

    “It is indicated in prospective studies that patients with ADHD, whether treated or not, are at increased risk for early death, suicide, and increased psychiatric comorbidity, particularly substance use disorders.71,72”

    From Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents (2019) · cites this paper as [71]

    The Introduction (page not provided) says ADHD is associated with high comorbidity, long-term morbidity and mortality, and that youths with ADHD and comorbid depression face greater risk of adverse outcomes, including suicide. It does not establish increased risk of early death or suicide in patients regardless of treatment status, or identify substance use disorders as a particularly increased comorbidity. The Discussion (page not provided) instead mentions substance use disorder in relation to a possible protective effect of medication. (LLM, conf=0.84)

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  • A Swedish national registers cohort of more than 38,000 individuals with ADHD found that ADHD medication was associated with a greater than 40% reduction in risk of depression three years later, with risk decreasing as medication duration increased, and depression was 20% less common during medicated periods.

    “A nationwide longitudinal cohort study using the Swedish national registers found that among more than 38,000 individuals with ADHD, ADHD medication was associated with a greater than 40% reduction in the risk for depression three years later. The risk decreased with the duration of ADHD medication use. Depression was 20% less common when patients received ADHD medication compared with periods”

    From The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder (2021) · cites this paper as Chang et al., 2016

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Authors
Chang, Z., D’Onofrio, B. M., Quinn, P. D., Lichtenstein, P., & Larsson, H.
Affiliations
  • Karolinska Institutet (SE)
  • Indiana University Bloomington (US)
  • Örebro University (SE)
Corresponding author
Chang, Zheng
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2016-12
Volume
80
Issue
12
Pages
916-922
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2016.02.018
PMC
PMC4995143
OpenAlex
W2278520419
Cited by
154
References
39
Citations by year
2026: 16 · 2025: 13 · 2024: 21 · 2023: 18 · 2022: 15 · 2021: 15 · 2020: 19 · 2019: 14 · 2018: 12 · 2017: 6 · 2016: 4
FWCI
9.17
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Vetenskapsrådet
  • National Institutes of Health (UL1TR001108, TL1TR001107)
  • National Institute of Mental Health (R01MH102221)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
Keywords
attention deficit hyperactivity disorder, ADHD medication, depression, psychiatric comorbidity, duration of drug use, mental illness, long-term risk
MeSH terms
Adolescent, Adult, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Child, Depressive Disorder, Female, Humans, Longitudinal Studies, Male, Middle Aged, Drug Prescriptions, Registries, Risk, Sweden, Time Factors, Adrenergic Uptake Inhibitors, Young Adult

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