Efficacy of Treatments for Opioid-Induced Constipation: Systematic Review and Meta-analysis

Nee, Judy; Zakari, Mohammed; Sugarman, Michael A.; Whelan, Julia; Hirsch, William; Sultan, Shahnaz; Ballou, Sarah; Iturrino, Johanna; Lembo, Anthony

doi:10.1016/j.cgh.2018.01.021

Cited by 85 publications

(70 citation statements)

References 40 publications

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“…Therapies that restore or protect healthy gut microbiota may be important for alleviating the side effects of prolonged opioid use. For example, oral methyl-naltrexone is an opioid antagonist currently used for the treatment of opioid-induced constipation [49], and has been shown to alleviate some of the negative symptoms of chronic opioids including constipation and hyperalgesia [50]. The evidence presented herein suggest gut-restricted opioid antagonists (such as methyl-naltrexone) may positively affect clinical outcomes of opioid treatment by blocking opioidinduced changes to the gut flora while maintaining analgesic efficacy.…”

Section: Discussionmentioning

confidence: 90%

The gut microbiota mediates reward and sensory responses associated with regimen-selective morphine dependence

Lee

Vuong²,

Nusbaum³

et al. 2018

Neuropsychopharmacol

141

121

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Opioid use for long-term pain management is limited by adverse side effects, such as hyperalgesia and negative affect. Neuroinflammation in the brain and spinal cord is a contributing factor to the development of symptoms associated with chronic opioid use. Recent studies have described a link between neuroinflammation and behavior that is mediated by a gut-brain signaling axis, where alterations in indigenous gut bacteria contribute to several inflammation-related psychopathologies. As opioid receptors are highly expressed within the digestive tract and opioids influence gut motility, we hypothesized that systemic opioid treatment will impact the composition of the gut microbiota. Here, we explored how opioid treatments, and cessation, impacts the mouse gut microbiome and whether opioid-induced changes in the gut microbiota influences inflammation-driven hyperalgesia and impaired reward behavior. Male C57Bl6/J mice were treated with either intermittent or sustained morphine. Using 16S rDNA sequencing, we describe changes in gut microbiota composition following different morphine regimens. Manipulation of the gut microbiome was used to assess the causal relationship between the gut microbiome and opioid-dependent behaviors. Intermittent, but not sustained, morphine treatment was associated with microglial activation, hyperalgesia, and impaired reward response. Depletion of the gut microbiota via antibiotic treatment surprisingly recapitulated neuroinflammation and sequelae, including reduced opioid analgesic potency and impaired cocaine reward following intermittent morphine treatment. Colonization of antibiotic-treated mice with a control microbiota restored microglial activation state and behaviors. Our findings suggest that differing opioid regimens uniquely influence the gut microbiome that is causally related to behaviors associated with opioid dependence.

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Section: Discussionmentioning

confidence: 90%

The gut microbiota mediates reward and sensory responses associated with regimen-selective morphine dependence

Lee

Vuong²,

Nusbaum³

et al. 2018

Neuropsychopharmacol

141

121

View full text Add to dashboard Cite

show abstract

“…When response to laxative therapy has not been sufficient, peripherally acting mu opioid receptor antagonists such as oral methylnaltrexone, [167][168][169][170][171][172] naloxegol, 173 or naldemedine, 174 opioid antagonists that work on receptors in the gastrointestinal system, can be used as a rescue when constipation is clearly related to opioid therapy 175 (methylnaltrexone is FDA approved for opioid-induced constipation in adults with advanced illness who are receiving palliative care; naloxegol and naldemedine are FDA approved for opioid-induced constipation in adults with chronic noncancer pain, including those with chronic pain related to previous cancer or treatment). Other second-line agents include lubiprostone (FDA approved for opioid-induced constipation in adults with noncancer pain including those with chronic pain related to prior cancer or treatment), 176,177 and linaclotide 178 (FDA approved for idiopathic constipation).…”

Section: Constipationmentioning

confidence: 99%

Adult Cancer Pain, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology

Swarm

Paice

Anghelescu

et al. 2019

Journal of the National Comprehensive Cancer Network

381

282

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In recent years, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adult Cancer Pain have undergone substantial revisions focusing on the appropriate and safe prescription of opioid analgesics, optimization of nonopioid analgesics and adjuvant medications, and integration of nonpharmacologic methods of cancer pain management. This selection highlights some of these changes, covering topics on management of adult cancer pain including pharmacologic interventions, nonpharmacologic interventions, and treatment of specific cancer pain syndromes. The complete version of the NCCN Guidelines for Adult Cancer Pain addresses additional aspects of this topic, including pathophysiologic classification of cancer pain syndromes, comprehensive pain assessment, management of pain crisis, ongoing care for cancer pain, pain in cancer survivors, and specialty consultations.

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“…Despite the growing recognition of the burden of OIC in cancer patients leading to the development of new drugs targeting the underlying cause, few speci c clinical guidelines for the management of OIC have been published [11,13,20,24]. The present Delphi consensus was intended to be a useful tool to provide practical recommendations based on the experience of different Spanish physicians experts on opioid use and OIC.…”

Section: Discussionmentioning

confidence: 99%

Delphi consensus on strategies in the management of opioid-induced constipation in cancer patients

Sarrió

Calsina-Berna

García

et al. 2020

Preprint

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Background: Opioid-induced constipation (OIC) is a frequent and bothersome adverse event related with opioid therapy in cancer patients. Despite the high prevalence, medical management of OIC is often uncertain. The current project aimed to investigate expert opinion on OIC management and provide practical recommendations to improve the clinical approach of OIC in cancer patient.Methods: A modified Delphi method was conducted involving 46 different physicians experts in OIC. Using a structured questionnaire of 67 items this project intended to seek consensus on aspects related to diagnosis, treatment, and quality of life of cancer patients suffering with OIC.Results: After two rounds, a consensus was reached in 91% of the items proposed, all in agreement. Agreement was obtained on OIC definition (95.7%). Objective and patient-reported outcomes included in that definition should be assessed routinely in clinical practice. Responsive to symptom changes and easy-to-use assessment tools were recommended (87.2%). Successful diagnosis of OIC requires increase clinicians awareness of OIC and proactivity to discuss symptoms with their patients (100%). Successful management of OIC requires individualization of the treatment (100%), regular revaluation once is established, and keeping it for the duration of opioid treatment (91.5%). Oral Peripherally Acting µ-Opioid Receptor Agonists (PAMORAs), were considered good alternatives for the treatment of OIC in cancer patients (97.9%). This drugs and laxatives can be co-prescribed if OIC coexist with functional constipation.Conclusions: The panelists, based on their expert clinical practice, presented a set of recommendations for the management of OIC in cancer patients.

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Efficacy of Treatments for Opioid-Induced Constipation: Systematic Review and Meta-analysis

Abstract: In a systematic review and meta-analysis, we found μ-opioid-receptor antagonists to be safe and effective for the treatment of OIC. Prescription-strength laxatives (prucalopride, lubiprostone) are slightly better than placebo in reducing OIC.

Cited by 85 publications

References 40 publications

The gut microbiota mediates reward and sensory responses associated with regimen-selective morphine dependence

The gut microbiota mediates reward and sensory responses associated with regimen-selective morphine dependence

Adult Cancer Pain, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology

Delphi consensus on strategies in the management of opioid-induced constipation in cancer patients

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