Gut reaction: study reveals opioid pain relievers with highest constipation risk

A study led by University of Manchester epidemiologists has revealed which opioid painkillers are most likely to be associated with constipation in patients with non-cancer pain. 

The largest ever study to evaluate the comparative safety of constipation across different opioids is published today (16/06/25). 

The study was funded by the Nuffield Foundation’s Oliver Bird Fund, which supports research to improve the social and economic well-being of people living with musculoskeletal conditions and Versus Arthritis. It was also supported by the National Institute for Health and Care Research (NIHR). 

Morphine, oxycodone, fentanyl and combination opioids, they found, were associated with a significantly higher risk of severe constipation when compared to codeine. 

Tramadol, on the other hand, was associated with the lowest risk of constipation when compared to codeine. 

Patients on greater than 50 morphine milligram equivalent (MME) per day - a universal measure of opioid strength- experienced the highest risk of severe constipation. Fifty MME per day is roughly equal to taking either 50mg of morphine or 33 mg of oxycodone each day.

 Guidance from the UK site recommends the dose above which opioid harms likely outweigh benefits is 120 MME per day. However, this is currently under review. 

The study was carried out using hospital electronic health records of 80,475 eligible patients in Northwest England between 2009 and 2020. 

Opioid exposure was measured using administered drug information from the hospital records, and a severe constipation event was defined as an administration of an enema or suppository. 

The study authors say that being aware of the relative risks allows healthcare professionals to better tailor pain management strategies to personal needs. It also allows more informed discussions with patients about their pain relief dose and type, including choosing one with a lower risk as appropriate. 

Senior author Dr Meghna Jani, NIHR Advanced Fellow and Senior Clinical Lecturer at The University of Manchester said: “Constipation is a frequent adverse event associated with opioid medications that can have a considerable impact on patients’ quality of life. 

“As well as the major impact on activities of daily living, opioid-induced constipation has also been associated with longer hospital stays, higher hospital costs, and increased emergency department visits.”

Estimates of constipation rates within electronic health records are likely to under-represent the true prevalence both in primary and secondary health care records, the researchers find.

This is because constipation may be seen as less serious and therefore not always coded, despite being mentioned.

Patients may also struggle to openly talk about their bowel habits with a health care professional, thereby not discussing it if they get admitted to hospital, or not seeking health advice when they do experience it.

She added: “Previously, we didn’t know enough about the risk associated with specific opioids, given the different ways they act on the body, as well as the effect of daily dose.

“This study will allow clinical prescribers and patients to make better shared decisions about what pain relief is best for them, to minimise the risks of this side effect of opioids, and thus improve patients’ quality of life.

“If patients need to be on opioids, we urge prescribers to be cautious with opioid dosing, and aim for the lowest effective dose to manage pain while mitigating the risk of constipation and other side effects.”

The paper: Comparative risk of severe constipation in patients treated with  opioids for non-cancer pain: a retrospective cohort study in Northwest England is available: