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

Abstract

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 on studies that investigated the effects of ADHD medication on behavioral and neuropsychiatric outcomes using linked prescription databases from the last ten years, and identified 40 studies from Europe, North America, and Asia. Among them, 18 have 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 9–58% for these outcomes. The within-individuals studies found no evidence of increased risks for suicidality and seizures. Replications 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 are less clear. We discussed time-varying confounding and other limitations which should be considered when interpreting results from pharmacoepidemiology studies. Further, we highlighted several knowledge gaps to be addressed in future research and implications for research on mechanisms of outcomes of ADHD medications.