Randomized controlled trials suggest that ADHD medication has beneficial short-term effects. The increasing use of ADHD medications is being heavily debated, however, because of concerns regarding the short- and long-term effects of ADHD medications. The overall objective for this proposal is to more precisely estimate the magnitude of the short- and long-term risks and benefits of ADHD medications on serious psychiatric (substance abuse, suicidal behavior, mania/bipolar disorder, and major depression) and neurological (seizures/epilepsy) outcomes by conducting advanced pharmaco-epidemiologic analyses in two large datasets that include prospective longitudinal information on prescribed ADHD medications and medical problems. We will use a Swedish cohort of 75,000 patients with a diagnosis of ADHD based on national registers. And, we will conduct analyses on a large US sample based on insurance claims, including 2.3 million patients with ADHD. The analyses in both datasets will use the same analytical approaches, including within-individual comparisons and advanced statistical techniques to account for stable and time-varying confounding. Our central hypothesis is that ADHD medication will be associated with reduced psychiatric and neurological problems and that risk for adverse outcomes (e.g., short-term seizures and long-term substance use problems) will be minor, especially when we compare the relations within individuals.
The first aim i s to examine the short-term effects of ADHD medications on these problems.
The second aim i s to examine the long-term effects of ADHD medications on these problems. The rationale for the proposed research is that rigorous pharmaco-epidemiologic studies-employing advanced designs and statistical analyses with large, population samples-can more precisely characterize the risks and benefits of ADHD medication. The significance of the proposed research is that the results will more precisely identify the specific risks and benefits associated with ADHD medication, which previous studies have been unable to adequately explore. The proposed analyses, which are based on the two large datasets, also will explore the generalizability of the findings across different national, cultural, and medical contexts. These efforts would directly inform medical practice and influence subsequent research in numerous fields, such as pharmaco-epidemiology and randomized controlled trials. The proposed research is innovative because the research team will analyze two datasets (in Sweden and the United States);combine within-individual comparisons with sophisticated analytical strategies to rule out confounding factors;and bring together a team of international researchers with expertise in the etiology and treatment of ADHD, pharmaco-epidemiology, quasi-experimental designs, and analyses of both datasets. We propose, therefore, to conduct the most comprehensive study of serious psychiatric and neurologic problems associated with ADHD medication to date.

Public Health Relevance

Although randomized controlled trials suggest that ADHD medication has beneficial short-term effects, there are major concerns regarding the short- and long-term risks and benefits of ADHD medications for serious psychiatric and neurologic outcomes. In order to better inform medical practice and guide subsequent translational research, the current proposal seeks support to conduct extensive analyses in two large, prospective longitudinal studies (one in Sweden and one in the United States) that contain information on prescribed ADHD medications and serious psychiatric and neurologic outcomes. The analyses will use within- individual comparisons-exploring the rates of these outcomes in the same individual during medication versus non-medication periods-and advanced statistical techniques to account for alternative explanations, such as confounding, for the observed associations with ADHD medication.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Program Officer
Rupp, Agnes
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Indiana University Bloomington
Schools of Arts and Sciences
United States
Zip Code
Brikell, Isabell; Ghirardi, Laura; D'Onofrio, Brian M et al. (2018) Familial Liability to Epilepsy and Attention-Deficit/Hyperactivity Disorder: A Nationwide Cohort Study. Biol Psychiatry 83:173-180
Lu, Yi; Sjölander, Arvid; Cederlöf, Martin et al. (2017) Association Between Medication Use and Performance on Higher Education Entrance Tests in Individuals With Attention-Deficit/Hyperactivity Disorder. JAMA Psychiatry 74:815-822
Quinn, Patrick D; Rickert, Martin E; Weibull, Caroline E et al. (2017) Association Between Maternal Smoking During Pregnancy and Severe Mental Illness in Offspring. JAMA Psychiatry 74:589-596
Quinn, Patrick D; Chang, Zheng; Hur, Kwan et al. (2017) ADHD Medication and Substance-Related Problems. Am J Psychiatry 174:877-885
Viktorin, Alexander; Rydén, Eleonore; Thase, Michael E et al. (2017) The Risk of Treatment-Emergent Mania With Methylphenidate in Bipolar Disorder. Am J Psychiatry 174:341-348
Quinn, Patrick D; Hur, Kwan; Chang, Zheng et al. (2017) Incident and long-term opioid therapy among patients with psychiatric conditions and medications: a national study of commercial health care claims. Pain 158:140-148
Skoglund, Charlotte; Brandt, Lena; D'Onofrio, Brian et al. (2017) Methylphenidate doses in Attention Deficit/Hyperactivity Disorder and comorbid substance use disorders. Eur Neuropsychopharmacol 27:1144-1152
Skoglund, Charlotte; Brandt, Lena; Almqvist, Catarina et al. (2016) Factors Associated With Adherence to Methylphenidate Treatment in Adult Patients With Attention-Deficit/Hyperactivity Disorder and Substance Use Disorders. J Clin Psychopharmacol 36:222-8
Quinn, Patrick D; Pettersson, Erik; Lundström, Sebastian et al. (2016) Childhood attention-deficit/hyperactivity disorder symptoms and the development of adolescent alcohol problems: A prospective, population-based study of Swedish twins. Am J Med Genet B Neuropsychiatr Genet 171:958-70
Chang, Zheng; D'Onofrio, Brian M; Quinn, Patrick D et al. (2016) Medication for Attention-Deficit/Hyperactivity Disorder and Risk for Depression: A Nationwide Longitudinal Cohort Study. Biol Psychiatry 80:916-922

Showing the most recent 10 out of 13 publications