That’s why a recent Danish study, which pointed out that discontinuation and switches to nonstimulant ADHD medications are common, sought to identify genetic, clinical, and sociodemographic factors influencing stimulant treatment initiation, discontinuation, and switch to nonstimulants in ADHD patients.
A key finding, reported in the American Journal of Psychiatry, is that having another psychiatric diagnosis is predictive of who is more likely to stop using the medications. The research study was conducted by The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) in Denmark.
One of the most common psychiatric disorders in childhood, ADHD usually is treated with stimulants, although some patients are placed on nonstimulants if their response isn’t appropriate to the first-line therapy.
To increase understanding of the dynamics, genetic and national register data for 9,133 individuals with ADHD were extracted from the Danish iPSYCH2012 sample, with researchers focusing on stimulant treatment initiation, discontinuation, and switch from prescriptions. For each stimulant-treatment outcome, the study team also assessed associations with polygenic risk scores (PRSs) for psychiatric disorders and clinical and sociodemographic factors. Genome-wide association studies (GWASs) and estimated single-nucleotide polymorphism heritability (h2SNP) also were included in the assessment.
While 81% of the sample initiated stimulant treatment, according to the report, 45% had discontinued stimulants and 15% switched to nonstimulants within 2 years.
Most associated with discontinuation were bipolar disorder PRS (hazard ratio [HR], 1.05; 95% CI, 1.02, 1.09) and schizophrenia PRS (HR, 1.07; 95% CI, 1.03, 1.11). The authors note that depression, bipolar disorder, and schizophrenia PRSs were marginally, but not significantly, associated with switching (HR range, 1.05-1.07).
On the other hand, researchers found no associations for ADHD and autism PRSs, when it came to noncompliance or changes in medication.
Overall, the authors determined that:
• Patients diagnosed with ADHD at age 13 years or older had higher rates of stimulant initiation, discontinuation, and switch (HR range, 1.27-2.01)
• Psychiatric comorbidities, in most cases, reduced rates of initiation (hazard ratio range, 0.84-0.88) and increased rates of discontinuation (HR range, 1.19-1.45) and switches (HR range, 1.40-2.08)
• The h2SNP estimates were not significantly different from zero, and no GWAS hits were identified for stimulant initiation or discontinuation. Still, a locus on chromosome 16q23.3 reached genome-wide significance for switch of medications.
“The study findings suggest that individuals with ADHD with higher polygenic liability for mood and/or psychotic disorders, delayed ADHD diagnosis, and psychiatric comorbidities have a higher risk for stimulant treatment discontinuation and switch to non-stimulants,” the authors conclude. “Despite the study’s limited sample size, one putative GWAS hit for switch was identified, illustrating the potential of utilizing genomics linked to prescription databases to advance ADHD pharmacogenomics.”
"We discovered that people who have another psychiatric diagnosis in addition to ADHD, for example tics, anxiety, bipolar disorder or some form of substance abuse, to a greater extent stop taking their stimulant medication or switch to a non-stimulant ADHD medication,” explained lead author Isabell Brikell, MSc, PhD, a researcher at iPSYCH.
Dr. Brikell suggested the findings could be related to a higher risk of side effects or a lower effect of stimulants in people with several diagnoses, adding, “It's important to understand why so many stop taking their ADHD medication. Prior research has shown that the treatment can have positive effects on important parameters such as school performance and a lower risk of accidents and injuries for people with ADHD.”
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