Adapted from ‘The cost of opioid-induced constipation’ (Kim Thomas, 2022).

Edited by Emma Cooper, Editor of Pf Magazine.

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This blog post examines the causes and diagnosis of opioid-induced constipation (OIC) and addresses effective routes to management for an improved quality of life.

Opioids are extremely effective painkillers that work by binding to receptors in the brain and spinal cord to relieve pain. Opioid-induced constipation (OIC) is part of a group of symptoms, collectively named opioid-induced bowel dysfunction (OIBD), that affect patients taking opioids. Studies suggest that OIC affects between 41% and 57% of patients taking opioids for pain (Cobo et al, 2021), and up to 87% of patients with terminal cancer using opioids (Cobo et al, 2021; Ahmedzai and Boland, 2010). Treating OIC is, however, extremely challenging.

Causes and diagnosis of OIC

As well as being present in the brain and spinal cord, opioid receptors are found in the gut, which means that the opioids can bind to the μ-receptors in the enteric system. When they bind to these receptors, they interfere with the body’s ability to move waste material through the intestines (Poulsen et al, 2015). The opioids inhibit gastric emptying and peristalsis in the gastrointestinal tract, resulting in the delayed absorption of medication and in increased absorption of fluid. The lack of fluid in the intestine leads to hardening of stool and constipation (Coluzzi et al, 2021).

The Rome IV criteria define OIC as ‘new or worsening symptoms of constipation when initiating, changing or increasing opioid therapy’ (Rome Foundation 2016). The criteria also states that these symptoms must include two or more of the following in at least 25% of defecations: straining, lumpy or hard stools, sensation of incomplete evacuation, sensation of anorectal blockage, use of manual manoeuvres to facilitate defecation, and fewer than three spontaneous bowel movements per week. In practice, however, the criteria are underused (Coluzzi et al, 2021).

The impact of OIC

The condition frequently has a negative impact on patients’ quality of life, including their ability to perform daily activities and work productively. They may also experience an increase in depression and anxiety. Some patients reduce or discontinue opioid treatment, preferring to experience the pain rather than the debilitating effects of OIC (Argoff et al, 2020).

OIC also has an economic burden. There is limited information about the cost to the NHS, though we do know that in 2018-19, the estimated annual spend by NHS England on constipation was £168 million (Bowel Interest Group, 2020).

The problem with laxatives

In people with OIC, laxatives are an ineffective treatment, as are bowel regimens, dietary changes, and lifestyle modifications. This is because they do not target the underlying cause – the opioid binding to the μ-receptors in the gastro-intestinal tract (Kumar et al, 2014).

Laxatives can also have unpleasant side effects. In one study of 198 patients taking opioid analgesics for at least one month, 73% had used laxatives at some point. Of these, 75% reported side effects, including gas, bloating or fullness, and a sudden urge to defecate. Approximately half of patients said laxatives interfered with work and social activities, and one fifth needed an overnight hospital stay because of their pain condition and/or constipation. Neither did laxatives improve the symptoms of constipation, as assessed by the Bowel Function Index (Emmanuel et al, 2017).

Using PAMORAs to treat OIC

Peripheral-acting mu opioid receptor antagonists (PAMORAs) are drugs that act directly on the mechanism causing OIC, combining with μ-receptors to inhibit the action of opioids in the gastrointestinal tract. Because PAMORAs reduce the effect of opioids in the gut without affecting how opioids work in the brain and spine, they enable the gastrointestinal system to function normally while maintaining the pain relief functions of opioids.

Addressing the problem

Healthcare professionals are often poorly informed about OIC and continue to treat it with ineffective laxatives rather than PAMORAs. One Italian multidisciplinary panel noted that use of the Rome IV criteria, which propose that OIC should be defined as new or worsening constipation when initiating, changing or increasing opioid therapy, mean that the early diagnosis of faecal stasis may be missed, particularly in older patients and those with cancer, and especially if bedridden (De Giorgio et al, 2021).

The panel also observed that not all specialists agree on the signs and symptoms of OIC specified in the Rome IV criteria, and recommend instead developing a symptom-based definition of OIC that is easy to apply in everyday clinical practice, both in community care settings (e.g. primary care and nursing homes) and in hospitals.

They note that current guidelines ‘do not provide a clear recommendation as to the frequency with which OIC should be evaluated’, and that therefore ‘constipation should be evaluated on a continuous basis in all patients who take an opioid.’

The recommendations made by the panel include proper education about OIC, stating: ‘Physicians of all specialties who treat patients on a long-term opioid, nurses, caregivers, and patients should be instructed about the risks of OIC and strategies for its prevention or treatment.’ The panel also recommends limiting interventions that rely on lifestyle changes or dietary and hydration changes, and that patients should not be left to solve the problem of OIC on their own.

Conclusions

The lack of physician awareness both of the impact of OIC and the appropriate treatments means that patients, many of them already seriously ill, often suffer unnecessarily. It is possible, however, to relieve symptoms through the use of better diagnosis and treatment.

In short, clinicians need to take a more proactive approach in the management of OIC, using a standard, symptom-based definition of OIC; educating themselves about treatment options; asking the patient regularly about symptoms; and making sure that patients receive therapy that manages their pain appropriately while avoiding the debilitating consequences of OIC.

To find out more about the impact of OIC, keep an eye out for the Bowel Interest Group’s latest report, The Cost of Opioid-induced Constipation, which will be published this summer and sets out to educate primary and secondary healthcare professionals in the management of OIC.

References

Ahmedzai, S H, & Boland, J. Constipation in people prescribed opioids. BMJ clinical evidence. 2010; 2407.

Argoff C. E. (2020). Opioid-induced Constipation: A Review of Health-related Quality of Life, Patient Burden, Practical Clinical Considerations, and the Impact of Peripherally Acting μ-Opioid Receptor Antagonists. The Clinical journal of pain, 36(9), 716–722. https://doi.org/10.1097/AJP.0000000000000852

Bowel Interest Group (2020). Cost of constipation report. 2020. Available from: https://bowelinterestgroup.co.uk/resources/cost-of-constipation-report-2020/

Cobo Dols M, Beato Zambrano C, Cabezón-Gutiérrez L, et al. KYONAL study. BMJ Supportive & Palliative Care. 2021 https://doi: 10.1136/bmjspcare-2020-002816

Coluzzi F, Alvaro D, Caraceni AT, Gianni W, Marinangeli F, Massazza G, Pinto C, Varrassi G, Lugoboni F. Common Clinical Practice for Opioid-Induced Constipation: A Physician Survey. J Pain Res. 2021; 14, 2255-2264
https://doi.org/10.2147/JPR.S318564

De Giorgio R, Zucco FM, Chiarioni G, et al. Management of Opioid-Induced Constipation and Bowel Dysfunction: Expert Opinion of an Italian Multidisciplinary Panel. Adv Ther. 2021; 38(7):3589-3621. https://doi: 10.1007/s12325-021-01766-y.

Emmanuel A, Johnson M, McSkimming P, Dickerson S. Laxatives Do Not Improve Symptoms of Opioid-Induced Constipation: Results of a Patient Survey. Pain Med. 2017; 18(10):1932-1940. https://doi: 10.1093/pm/pnw240.

Kumar, L., Barker, C., Emmanuel, A. (2014). Opioid-Induced Constipation: Pathophysiology, Clinical Consequences, and Management, Gastroenterology Research and Practice. 2014. https://doi.org/10.1155/2014/141737

Poulsen, J L, Brock, C, Olesen, A E, Nilsson, M, & Drewes, A M. Evolving paradigms in the treatment of opioid-induced bowel dysfunction. Therapeutic Advances in Gastroenterology. 2015; 360–372. https://doi.org/10.1177/1756283X15589526

Rome Foundation. Appendix A: Rome IV Diagnostic Criteria for FGIDs. 2016. Available at: https://theromefoundation.org/rome-iv/rome-iv-criter