Uncovering genetic predictors for extreme morphine responses in infants and children

Morphine and fentanyl are commonly prescribed for relief of major pain in infants and children; however, responses range from inadequate pain relief (requiring higher doses/other analgesics) to adverse effects (e.g., respiratory depression, hypotension, allergic reaction), and the long-term consequences of opioid use on the developing brain remain unclear [1,2]. Several genes are associated with opioid response [1]; however, inconsistent findings have hindered development of pharmacogenetic tests to predict undesirable responses. Importantly, patients with extreme opioid responses (adverse effects at low doses or no pain relief despite high doses) are likely to harbour genetic variants with large effects, increasing the ability to detect associations. We aim to investigate previously-published, and identify novel, genetic variants in extreme responders to ultimately improve morphine/fentanyl safety and effectiveness in children.