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Biol Psychiatry. 2019 Sep 1;86(5):335-343. doi: 10.1016/j.biopsych.2019.04.009. Epub 2019 Apr 17.

Risks and Benefits of Attention-Deficit/Hyperactivity Disorder Medication on Behavioral and Neuropsychiatric Outcomes: A Qualitative Review of Pharmacoepidemiology Studies Using Linked Prescription Databases.

Author information

1
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Electronic address: zheng.chang@ki.se.
2
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
3
Department of Applied Health Science, School of Public Health, Bloomington, Indiana.
4
Social Genetic and Developmental Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
5
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana.
6
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; School of Medical Sciences, Örebro University, Örebro, Sweden.

Abstract

Attention-deficit/hyperactivity disorder (ADHD) medication is one of the most commonly prescribed medication classes in child and adolescent psychiatry, and its use is increasing rapidly in adult psychiatry. However, major questions and concerns remain regarding the benefits and risks of ADHD medication, especially in real-world settings. We conducted a qualitative systematic review of studies that investigated the effects of ADHD medication on behavioral and neuropsychiatric outcomes using linked prescription databases from the last 10 years and identified 40 studies from Europe, North America, and Asia. Among them, 18 used within-individual designs to account for confounding by indication. These studies suggested short-term beneficial effects of ADHD medication on several behavioral or neuropsychiatric outcomes (i.e., injuries, motor vehicle accidents, education, substance use disorder), with estimates suggesting relative risk reduction of 9% to 58% for these outcomes. The within-individual studies found no evidence of increased risks for suicidality and seizures. Replication studies are needed for several other important outcomes (i.e., criminality, depression, mania, psychosis). The available evidence from pharmacoepidemiology studies on long-term effects of ADHD medication was less clear. We discuss time-varying confounding and other limitations that should be considered when interpreting results from pharmacoepidemiology studies. Furthermore, we highlight several knowledge gaps to be addressed in future research and implications for research on mechanisms of outcomes of ADHD medications.

KEYWORDS:

ADHD medication; Long-term outcomes; Pharmacoepidemiology; Real-world evidence; Short-term outcomes; Within-individual design

PMID:
31155139
PMCID:
PMC6697582
[Available on 2020-09-01]
DOI:
10.1016/j.biopsych.2019.04.009

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