Practice update: Refractory constipation
Longstanding concerns about chronic stimulant laxative use are described as unfounded.
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01/07/2026
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by Doug Brunk
“Defecatory disorders remain common and frequently under-recognized, and failure to address them early can lead to unnecessary escalation and poor outcomes,” he said. “Failure to adequate test for and treat these disorders is one of the most common causes for refractory symptoms that I see in my tertiary referral practice.”
2. Objectively documenting slow colonic transit — ideally both off therapy and on maximal therapy — before considering surgical options is emphasized.
“Symptoms alone are insufficient to guide major interventions, and physiologic confirmation is critical,” he said.
According to Dr. Staller, these factors “substantially influence outcomes and are essential components of preoperative assessment,” he said. “Since constipation can reflect both motor and sensory dysfunction, realizing that these disorders commonly affect other parts of the GI tract and central nervous system is key.”
Another practice advice statement calls for clinicians to look beyond the gut for secondary causes of constipation such as medications, disordered eating, endometriosis, or comorbid neurological diseases such as Parkinson’s disease or multiple sclerosis. “Medications are among the most common iatrogenic causes of CC including opioid-induced or opioid exacerbated constipation,” the authors wrote. “Other frequent secondary causes include anticholinergic agents such as antipsychotics and iron supplements.”
The update strongly encourages optimization of medical therapy before escalating care. In addition to FDA-approved agents such as linaclotide, plecanatide, and prucalopride, the authors support rational combination therapy using agents with different mechanisms of action. Longstanding concerns about chronic stimulant laxative use are described as unfounded, which Dr. Staller said may surprise some clinicians. “Additionally, the growing role of non-pharmacologic interventions—such as vibrating capsules, electroacupuncture, and transanal irrigation—may be unexpected, particularly for clinicians trained when therapeutic options were far more limited,” he said.
According to Dr. Staller, surgical management generated the most discussion during development of the practice update. While colectomy can be effective in carefully selected patients, “it is also associated with significant morbidity and variable long-term satisfaction,” he said. “Determining how strongly to frame recommendations around relative contraindications, psychological assessment, and the role of temporary diversion required careful consideration. We wanted to be clear and evidence-based without oversimplifying a complex clinical decision.” He and his coauthors also discussed how to position off-label and non-pharmacologic therapies.
“Although the evidence base is still evolving, these approaches are increasingly used in practice, and we felt it was important to provide clinicians guidance since we all use these approaches in our own practices,” he said.
The authors acknowledged that significant knowledge gaps remain in the optimal management of RC, including the lack of reliable predictors of treatment response, particularly for advanced pharmacologic therapies and surgical interventions. They also called for comparative studies evaluating combination treatments and integrated medical and behavioral strategies.
“Finally, longer-term outcomes data for newer agents and device-based therapies, as well as more work on the interaction between psychological factors and motility, would meaningfully advance the field,” Dr. Staller said.
Dr. Staller was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. He and his coauthors disclosed being a consultant for and/or receiving research funding from several pharmaceutical companies.
Summary content
7 Key Takeaways
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Developed a paper-based colorimetric sensor array for chemical threat detection.
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Can detect 12 chemical agents, including industrial toxins.
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Production cost is under 20 cents per chip.
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Utilizes dye-loaded silica particles on self-adhesive paper.
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Provides rapid, simultaneous identification through image analysis.
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Inspired by the mammalian olfactory system for pattern recognition.
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Future developments include a machine learning-enabled reader device.
The guidelines emphasize four-hour gastric emptying studies over two-hour testing. How do you see this affecting diagnostic workflows in practice?
Dr. Staller: Moving to a four-hour solid-meal scintigraphy will actually simplify decision-making. The two-hour reads miss a meaningful proportion of delayed emptying; standardizing on four hours reduces false negatives and the “maybe gastroparesis” purgatory that leads to repeat testing. Practically, it means closer coordination with nuclear medicine (longer slots, consistent standardized meal), updating order sets to default to a four-hour protocol, and educating front-line teams so patients arrive appropriately prepped. The payoff is fewer equivocal studies and more confident treatment plans.
Metoclopramide and erythromycin are the only agents conditionally recommended for initial therapy. How does this align with what is being currently prescribed?
Dr. Staller: This largely mirrors real-world practice. Metoclopramide remains the only FDA-approved prokinetic for gastroparesis, and short “pulsed” erythromycin courses are familiar to many of us—recognizing tachyphylaxis limits durability. Our recommendation is “conditional” because the underlying evidence is modest and patient responses are heterogeneous, but it formalizes what many clinicians already do: start with metoclopramide (lowest effective dose, limited duration, counsel on neurologic adverse effects) and reserve erythromycin for targeted use (exacerbations, bridging).
Several agents, including domperidone and prucalopride, received recommendations against first-line use. How will that influence discussions with patients who ask about these therapies?
Dr. Staller: Two points I share with patients: evidence and access/safety. For domperidone, the data quality is mixed, and US access is through an FDA IND mechanism; you’re committing patients to EKG monitoring and a non-trivial administrative lift. For prucalopride, the gastroparesis-specific evidence isn’t strong enough yet to justify first-line use. So, our stance is not “never,” it’s just “not first.” If someone fails or cannot tolerate initial therapy, we can revisit these options through shared decision-making, setting expectations about benefit, monitoring, and off-label use. The guideline language helps clinicians have a transparent, evidence-based conversation at the first visit.
The guidelines suggest reserving procedures like G-POEM and gastric electrical stimulation for refractory cases. In your practice, how do you decide when a patient is “refractory” to medical therapy?
Dr. Staller: I define “refractory” with three anchors.
1. Adequate trials of foundational care: dietary optimization and glycemic control; an antiemetic; and at least one prokinetic at appropriate dose/duration (with intolerance documented if stopped early).
2. Persistent, function-limiting symptoms: ongoing nausea/vomiting, weight loss, dehydration, ER visits/hospitalizations, or malnutrition despite the above—ideally tracked with a validated instrument (e.g., GCSI) plus nutritional metrics.
3. Objective correlation: delayed emptying on a standardized 4-hour solid-meal study that aligns with the clinical picture (and medications that slow emptying addressed).
At that point, referral to a center with procedural expertise for G-POEM or consideration of gastric electrical stimulation becomes appropriate, with multidisciplinary evaluation (GI, nutrition, psychology, and, when needed, surgery).
What role do you see dietary modification and glycemic control playing alongside pharmacologic therapy in light of these recommendations?
Dr. Staller: They’re the bedrock. A small-particle, lower-fat, calorie-dense diet—often leaning on nutrient-rich liquids—can meaningfully reduce symptom burden. Partnering with dietitians early pays dividends. For diabetes, tighter glycemic control can improve gastric emptying and symptoms; I explicitly review medications that can slow emptying (e.g., opioids; consider timing/necessity of GLP-1 receptor agonists) and encourage continuous glucose monitor-informed adjustments. Pharmacotherapy sits on top of those pillars; without them, medications will likely underperform.
The guideline notes “considerable unmet need” in gastroparesis treatment. Where do you think future therapies or research are most urgently needed?
Dr. Staller: I see three major areas.
1. Truly durable prokinetics: agents that improve emptying and symptoms over months, with better safety than legacy options (e.g., next-gen motilin/ghrelin agonists, better-studied 5-HT4 strategies).
2. Endotyping and biomarkers: we need to stop treating all gastroparesis as one disease. Clinical, physiologic, and microbiome/omic signatures that predict who benefits from which therapy (drug vs G-POEM vs GES) would transform care.
3. Patient-centered trials: larger, longer RCTs that prioritize validated symptom and quality-of-life outcomes, include nutritional endpoints, and reflect real-world medication confounders.
Our guideline intentionally highlights these gaps to hopefully catalyze better trials and smarter referral pathways.
Dr. Staller is with the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston.