“In daily clinical practice, it’s a matter of trial and error. We prescribe one opiate and we titrate the dose based on effect and side effects,” Dr. Oosten said. “We have to search for as long as needed to find the right type of opiate in the right dose. That won’t change based on the results of this review.”

The findings, however, shed new light on the lesser-known notion that patient-reported side effects are difficult to pin down because there are a variety of symptoms and concerns that can occur from the cancer, other concurrent illnesses, or the treatments themselves, including pain medicines, American Society of Clinical Oncology expert Andrew Epstein, MD, told Clinical Pain Advisor.


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“The takeaway is not necessarily that more studies need to be done on the exact prevalence of the side effects of opiates, but that clinicians need to be aware of the side effect potential of opiates. [They should] be well educated about the possibilities of one drug causing side effects but not another, strategies that can help people through side effects from opiates, and other pearls of wisdom about opiates in cancer pain,” Dr. Epstein said.

Dr. Epstein is a gastrointestinal medical oncologist and palliative medicine doctor from Memorial Sloan Kettering Cancer Center in New York, and was not involved in the study.

Wide Heterogeneity in Assessment and Reporting

Analyzing data from 25 studies, including 9 randomized control trials and 16 cohort studies that described 31 treatment cohorts with different opioids, researchers found that nausea rates were dose-related and varied from 3% to 85%. The differences in reported adverse events across the studies made comparing the different treatments impossible, the authors write.

Compared with nausea, vomiting was reported as a side effect in fewer studies. Overall rates ranged from 4% to 50%. Four studies combined nausea and vomiting as a single side effect, and 3 other studies showed a higher rate of vomiting than nausea.  Researchers were unable to make a comparison between opioids based on these data.  

The constipation rate varied from 5% to 97%, and was in line with that of nausea; study data suggested a dose-effect relationship for morphine, and possibly fentanyl.