Efficacy of pharmacological therapies for the treatment of opioid-induced constipation: systematic review and network meta-analysis

Luthra, Pavit; Burr, Nicholas; Brenner, Darren M.; Ford, Alexander C

doi:10.1136/gutjnl-2018-316001

Cited by 58 publications

(60 citation statements)

References 63 publications

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“…Expert Group of the European Society of Medical Oncology and Polish Association for Palliative Medicine recommend a consideration of PAMORA in the management of OIC [40,41]. Current data from clinical studies and systematic reviews indicate that naldemedine is an effective and generally well-tolerated treatment option for OIC in patients with cancer pain or chronic non-cancer pain, with the convenience of once-daily oral dosing [42,43].…”

Section: Discussionmentioning

confidence: 99%

The role of naldemedine in the treatment of patients with opioid-induced constipation

Leppert

2019

Palliat Med Pract

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Opioid-induced bowel dysfunction (OIBD) and opioid-induced constipation (OIC) significantly decrease patients' quality of life (QoL), lead to complications and opioid non-compliance resulting in pain exacerbation. Traditional laxatives are first-line preventive and therapeutic measures, although they display limited efficacy and several adverse effects (AE). Non-pharmacology measures, prokinetics, opioid switch, all have little evidence and do not target OIBD and OIC pathophysiology both associated with activation of predominantly µ-opioid receptors mostly peripherally in the gastrointestinal (GI) tract. A combination of prolonged-release (PR) oxycodone with PR naloxone in one tablet with a ratio of 2:1 is available, although limitations include maximal daily dose of 160 mg/80 mg, respectively, and normal liver function. Peripherally acting µ-opioid receptor antagonists (PAMORA) block opioid receptors in the GI tract without compromising analgesia as they do not cross the blood-brain barrier. Currently three drugs are available: methylnaltrexone, naloxegol and naldemedine. Naldemedine has proven efficacy superior to placebo in the treatment of OIC in both cancer and non-cancer patients while improving patient-reported constipation symptoms and patients' QoL. It is well tolerated with mostly mild to moderate intensity GI adverse effects such as abdominal, pain, nausea, and diarrhea, without compromising analgesia. Naldemedine dosing is convenient as it is administered once daily by an oral route. Moreover, naldemedine may be safely used in patients with renal failure and mild to moderate hepatic impairment. Effective prevention and treatment of OIC is of paramount importance in patients receiving long-term opioid therapy.

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Section: Discussionmentioning

confidence: 99%

The role of naldemedine in the treatment of patients with opioid-induced constipation

Leppert

2019

Palliat Med Pract

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“…nalexagol, naldemedine, methylnaltrexone) alleviate the symptoms of OIC by blocking the mu-opioid receptors within the GI tract, but as they do not cross the blood-brain barrier they do not diminish the central analgesic effect of opioids nor induce withdrawal symptoms. A systematic review and network meta-analysis of randomized controlled trials has found PAMORAs to be superior to placebo for the treatment of OIC [37]. A recent European expert consensus statement on OIC advises PAMORAs to be prescribed if standard laxatives have failed, which will be the case in up to 50% of cases [36].…”

Section: Peripherally Acting Mu-opioid Receptor Antagonists (Pamoras)mentioning

confidence: 99%

An approach to the diagnosis and management of Rome IV functional disorders of chronic constipation

Aziz

Whitehead

Palsson

et al. 2020

Expert Review of Gastroenterology & Hepatology

198

123

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Introduction: Chronic constipation is highly prevalent, affecting between 10% and 15% of the population. The Rome IV criteria categorizes disorders of chronic constipation into four subtypes: (a) functional constipation, (b) irritable bowel syndrome with constipation, (c) opioid-induced constipation, and (d) functional defecation disorders, including inadequate defecatory propulsion and dyssynergic defecation. The initial management approach for these disorders is similar, focusing on diet, lifestyle and the use of standard over-the-counter laxatives. If unsuccessful, further therapy is tailored according to subtype. Areas covered: This review covers the definition, epidemiology, diagnostic criteria, investigations and management of the Rome IV disorders of chronic constipation. Expert opinion: By adopting a logical step-wise approach toward the diagnosis of chronic constipation and its individual subtypes, clinicians have the opportunity to tailor therapy accordingly and improve symptoms, quality of life, and patient satisfaction.

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“…There have been many studies aiming to explore methods to facilitate postoperative GI recovery, including the following: 1) multimodal analgesia to reduce the use of opioids, e.g., other analgesic methods and non-steroidal anti-in ammatory drugs (NSAIDs) [20,21]. 2) laparoscopic surgery [22]; 3) goal-directed uid therapy [22]; 4) early enteral nutrition [23]; 5) gum chewing [24]; 6) opioid receptor antagonist [25]; 7) traditional Chinese medicine [26]. All of these methods play a limited role.…”

Section: Incidence and Degree Of Postoperative Abdominal Bloatingmentioning

confidence: 99%

Effect of Stellate Ganglion Block on Postoperative Recovery of Gastrointestinal Function in Patients Undergoing Surgery with General Anaesthesia: A Meta-Analysis.

Wen

Wang

Zhang

et al. 2020

Preprint

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Background: The return of normal gastrointestinal function is an important signal of postoperative recovery in patients undergoing surgery with general anaesthesia, especially for abdominal surgery. Current methods to resolve this problem are conservative, and the effects are sometimes limited. We aimed to summarize the effects of stellate ganglion block(SGB) on the recovery of gastrointestinal function to explore methods for anaesthesiologists to contribute to postoperative patient recovery. RuMethods: Selected databases were searched for relevant studies. Study quality was assessed according to the Cochrane Collaboration’s tool for assessing risk of bias. Data extraction was performed independently. The time to peristaltic sound resumption, flatus, postoperative eating and the incidence and degree of abdominal bloating were compared between stellate ganglion and control groups. Meta-analysis was performed using Review Manager software. Results: In total, 281 studies were identified after searching for relevant articles, and five articles with data for 274 patients were eligible for this analysis. Regarding postoperative flatus time, SGB caused a mean reduction of 15 hours for different surgeries; after excluding a study causing heterogeneity, the mean reduction was still more than 6 hours. For gastrointestinal surgery, the mean reduction was approximately an entire day. When evaluating the recovery of peristaltic sounds in different surgeries, SGB promoted the recovery of regular bowl sounds by an average of 14.67 hours earlier than the control. With regard to nutrients, SGB shortened the total parenteral nutrition time by more than 50 hours in gastrointestinal surgery. Finally, SGB prevented the occurrence of postoperative abdominal bloating without influencing its degree. No complications related to SGB were reported. Conclusion: SGB promotes postoperative gastrointestinal recovery in patients undergoing different surgeries with general anaesthesia.

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Efficacy of pharmacological therapies for the treatment of opioid-induced constipation: systematic review and network meta-analysis

Abstract: In network meta-analysis, naloxone and naldemedine appear to be the most efficacious treatments for OIC. Naloxone was the safest of these agents.

Cited by 58 publications

References 63 publications

The role of naldemedine in the treatment of patients with opioid-induced constipation

The role of naldemedine in the treatment of patients with opioid-induced constipation

An approach to the diagnosis and management of Rome IV functional disorders of chronic constipation

Effect of Stellate Ganglion Block on Postoperative Recovery of Gastrointestinal Function in Patients Undergoing Surgery with General Anaesthesia: A Meta-Analysis.

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