Genes Play a Role in Opioid Side Effects

Genes Play a Role in Opioid Side Effects

Genes play a significant role in determining which patients will suffer from respiratory depression, nausea, itchiness and other side effects from painkilling opiates, according to a Stanford University School of Medicine study. Researchers also found that genetics play a key role in determining which patients will become addicted to opioids such as morphine, methadone and oxycodone.

“One of the most hated side effects of these opiates, nausea, is strongly inherited,” said Martin Angst, MD, a professor of anesthesia and director of the Stanford Human Pain Research Laboratory.

Angst is one of two principal investigators for the study, which was published in the journal Anesthesiology. The study was prompted by earlier genetic studies in animals that showed a strong genetic component in response to opiates.

“Our findings strongly encourage the use of downstream molecular genetics to identify patients who are more likely or less likely to benefit from these drugs — to help make decisions on how aggressive you want to be with treatment, how carefully you monitor patients and whether certain patients are suitable candidates for prolonged treatment,” said Angst, who adds that further study of the role genes play could lead to personalized treatment plans for patients needing opioids.

Treatment with opiates is tricky because some patients may require 10 times the dose of the painkillers to get the same pain relief as others. Some patients may also have side effects, while others have none. And some may be able to take opioids for months with little potential for addiction, while others are at risk within weeks.

“We rely heavily on narcotics as the cornerstone medication for the relief of pain,” said Angst. “Yet we don’t know the answers to fundamental questions, such as why some people ‘like’ narcotics more than others — drug liking and disliking could be key in determining addiction potential.”

Researchers recruited 121 twin pairs for the randomized, double-blind and placebo-controlled study. Pain sensitivity was measured by applying heat and by immersing a hand in ice-cold water, both before and during an infusion of the opiate alfentanil, a short-acting painkiller. Researchers also compared the mental acuity, breathing, nausea, itching, and drug “liking” and “disliking” between identical twins, non-identical twins and non-related subjects. They found that identical twins are more similar in their responses to opiates than non-identical twins, suggesting that genes play a significant role.

Age was also associated with greater respiratory depression and drug-induced slowing of mental acuity. Older participants in the study were more likely to “dislike” taking opioids, which is consistent with lower rates of opioid abuse in aging patients with chronic pain.

“Since side effects are common among patients who use opioid medications, it will be beneficial to use such research to help at-risk patients avoid serious, life-threatening complications,” said David Clark, MD, PhD, professor of anesthesia and the other principal investigator for the study.

The study was funded by a grant from the National Institute on Drug Abuse.

Authored by: Pat Anson, Editor