Genes May Play Part in Opioid Side Effects

The respiratory depression and nausea often experienced by patients on opioid therapy appears to have some genetic component, researchers found.

In a twin study, genetic effects accounted for almost 60% of the response variance in nausea and 30% of the variance in respiratory depression, Martin Angst, MD, of Stanford University in Palo Alto, Calif., and colleagues reported online in Anesthesiology.

“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,” Angst said in a statement.

Opioids are a mainstay of pain management, but they carry side effects such as respiratory depression, sedation, nausea, and pruritus, as well as addiction.

However, there have been few studies looking at the contributions of genetic and environmental factors to patient response to opioids.

So Angst and colleagues conducted a twin study of 114 monozygotic and dizygotic twin pairs who were given either an infusion of saline placebo or alfentanil (Alfenta) - chosen for its quick onset and offset of action.

They found that there was significant heritability for both respiratory depression and nausea, with genetic effects accounting for 30% and 59% of variance in response, respectively.

Genetic factors also appeared to play a role in patients’ dislike of the drugs, accounting for 36% of the variance, the researchers reported.

“Opioid disliking may constitute a useful and easily measurable index phenotype to assess the abuse potential of opioids in future research,” they wrote.

There were other factors that weren’t necessarily found to be inherited, but still had a strong familial effect, which is due to shared genetic and environmental factors, the researchers said.

These included sedation, pruritus, and dizziness, with familial effects accounting for up to 29%, 38%, and 39% of the variance in response, respectively.

There was also a significant familial effect for drug liking, which accounted for up to 26% of response variance, they reported, noting that a “failure to detect heritability per se does not preclude relevant genetic effects.”

Angst and colleagues also found that covariates such as age, sex, race, ethnicity, education, mood, and depression affected sedation, pruritus, drug liking and disliking, and dizziness. In particular, age was associated with greater respiratory depression and drug-induced slowing of cognitive speed, they found.

Also, older age was associated with greater drug disliking, which is consistent with lower rates of opioid abuse in aging patients with chronic pain, they wrote.

They concluded that genetic, environmental, and demographic factors “work together to control adverse and reinforcing opioid responses, but contribute differently to specific responses.”

The researchers reported no conflicts of interest.

Primary source: Anesthesiology
Source reference: Angst MS, et al “Aversive and reinforcing opioid effects: A pharmacogenomic twin study” Anesthesiol 2012; 117: 22-37.

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