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PSYCHOPHARMACOLOGY
Factors Associated With Stimulant Treatment Outcomes in ADHD
July 9, 2021   

Stimulant medications are the first-line recommended treatment for attention deficit hyperactivity disorder (ADHD); however, many patients discontinue treatment or switch to nonstimulant ADHD medications. A recent study investigated the genetic, clinical, and sociodemographic factors that influence stimulant treatment initiation, discontinuation, and switch to nonstimulant medications in ADHD. The study included a sample of 9,133 Danish individuals of European ancestry diagnosed with ADHD. Polygenic risk scores (PRS; weighted sum of an individual’s phenotype-associated risk alleles) for ADHD, autism spectrum disorder (ASD), depression, bipolar disorder, and schizophrenia were included in analyses. Eighty-one percent of patients with ADHD initiated treatment with a stimulant medication. Among initiators, 45% discontinued treatment and 15% switched to nonstimulants within 2 years of stimulant initiation. PRSs for bipolar disorder (hazard ratio [HR]=1.05, 95% confidence interval [CI]=1.02, 1.09) and schizophrenia (HR=1.07, 95% CI=1.03, 1.11) were associated with discontinuation. Female sex was associated with higher rates of switching (HR=1.17, 95% CI=1.03, 1.33). Being diagnosed with ADHD at age 13 or older was associated with higher rates of initiation (HR=1.27, 95% CI=1.17, 1.38), discontinuation (HR=2.01, 95% CI=1.77, 2.27), and switching (HR=1.91, 95% CI=1.53, 2.39). Low maternal education was associated with lower rates of initiation (hazard ratio=0.94, 95% CI=0.90, 0.99) and low paternal income with higher rates of discontinuation (HR=1.11, 95% CI=1.03, 1.20). A genome-wide association study (GWAS) analysis detected one locus on chromosome 16q23.3 that reached genome-wide significance for switching. AC024590.1 and RN7SKP190 were identified as the most proximal genes of the locus; RN7SKP190 has been associated with theoretically relevant traits, such as body mass index, blood pressure, and educational attainment. Figure 1 includes all factors associated with ADHD treatment outcomes. Overall, given the modest effects on ADHD treatment outcomes by the evaluated risk factors, particularly PRS, utilization of multifactorial prediction may be needed to identify individuals with ADHD at high risk of suboptimal treatment outcomes.

Figure 1. Factors Associated with Stimulant Treatment Outcomes.
a Comorbid obsessive-compulsive disorder (OCD), bipolar disorder, and substance use disorder were associated with lower rates of initiation (hazard ratio range, 0.59-0.88); associations of comorbid bipolar disorder and substance use disorder were driven by individuals diagnosed with ADHD during adolescence or adulthood, as there were too few comorbid cases (N>10) to estimate hazard ratios in children.
b Comorbid oppositional/defiant/conduct disorder, tics, anxiety, and substance use disorder were associated with higher rates of switching to nonstimulants (hazard ratio range, 1.41-2.08); estimates stratified by age at first ADHD diagnosis showed that comorbid depression (hazard ratio=3.43, 95% CI=1.53, 7.71) was associated with switching in children but not in adolescents and adults; associations of comorbid substance use disorder were driven by individuals diagnosed with ADHD during adolescence or adulthood, as there were too few comorbid cases (N>10) to estimate hazard ratios in children.
c Comorbid autism spectrum disorder (ASD), anxiety, bipolar disorder, and substance use disorder were associated with higher rates of discontinuation (hazard ratio range, 1.18-1.46); estimates stratified by age at first ADHD diagnosis showed that comorbid ASD (hazard ratio=1.41, 95% CI=1.24, 1.60) and depression (hazard ratio=3.05, 95% CI=1.76, 5.28) were associated with discontinuation in children but not in adolescents and adults; associations of comorbid bipolar disorder and substance use disorder were driven by individuals diagnosed with ADHD during adolescence or adulthood, as there were too few comorbid cases (N>10) to estimate hazard ratios in children. ADHD: attention deficit hyperactivity disorder; PRS: polygenic risk score.

Reference:

Briskell I et al. Am J Psychiatry 2021; epub ahead of print. Abstract


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Topic: ADHD