Tramadol associated with lower risk of constipation than codeine - study

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By Olivia Bowthorpe

Hospitalised patients given tramadol for non-cancer pain relief were 20% less likely to experience severe constipation than those given codeine, results of a UK analysis have shown.

Conversely, morphine, oxycodone, fentanyl and a combination of opioids were associated with a 59%, 46%, 37% and 85% higher risk for constipation, respectively when compared to codeine, Dr Meghna Jani, senior clinical lecturer at the University of Manchester, and colleagues have reported in BMC Medicine.¹

Dr Jani told Doctors.net.uk: “Constipation is a common but often under-discussed side effect of opioid therapy. Patients can often find it difficult to talk about the impact it may have on their daily lives with health care professionals.”

While caution was necessary, "some patients do require opioids in the short-term for pain relief,” Dr Jani added, “therefore choosing the safest evidenced-based option within the class can be helpful."

The analysis used the electronic health records of 80,475 adult patients who were hospitalised in the North-West of England between 2009 and 2020, and who had been treated with opioids.

Only severe constipation was included in the analysis and this was defined as that requiring an enema or suppository to alleviate.

Results showed that patients receiving opioid doses of 50 morphine milligram equivalent (MME) per day or higher were significantly more likely to experience severe constipation than those who were given doses below this threshold.

Daily opioid doses of 50 MME or more nearly doubled the risk for constipation compared to doses under 50 MME.

Giving a patient a combination of opioids rather than was linked to an 85% higher risk of constipation.

"These findings help support more personalised prescribing decisions with patients in those who require opioids,” Dr Jani said. They could also “encourage proactive discussions about opioid tapering in those already receiving them to help manage their side effects.”

As to why tramadol was associated with a significantly lower risk of severe constipation as compared to codeine in the study, the team suggested that it may be to do with the drug’s mechanism of action which was different to other opioids.

The study “suggests the merit of considering tramadol as a lower-risk alternative in those requiring opioids, which may be especially valuable for patients already at risk for or concerned about [severe constipation]," the team wrote.

They observed that the Faculty of Pain Medicine recommended an upper dose for opioids of no more than 120 MME per day before the harms would outweigh the benefits of treatment.

However their study was “more aligned with a lower recommended threshold of [below] 50 MME/day.”

This was “consistent with the US Centres for Disease Control and Prevention opioid prescribing guidelines for pain," they said.

Reference:

1. Yimer B, Soomro M, et al. Comparative risk of severe constipation in patients treated with opioids for non-cancer pain: a retrospective cohort study in Northwest England. BMC Med Online 2025 [full text]

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