How to manage decreased gut motility in a patient taking lurasidone (Latuda)?

Management of Lurasidone-Induced Decreased Gut Motility

First, immediately review and discontinue or reduce any additional medications that impair gut motility, particularly opioids, anticholinergics, and calcium channel blockers, as these are primary contributors to intestinal dysmotility and must be addressed before initiating prokinetic therapy. 1, 2

Initial Assessment and Medication Review

• Document all current medications with particular attention to opioids, anticholinergics (including cyclizine, antidepressants, phenothiazines), and calcium channel blockers, as these directly inhibit intestinal motility and compound the anticholinergic effects of lurasidone 2, 1, 3

• List symptoms in order of importance to the patient (constipation, abdominal pain, distension, nausea/vomiting) as this predicts treatment response and guides therapy selection 2, 3

• Exclude mechanical obstruction with CT abdomen with oral contrast before attributing symptoms solely to medication-induced dysmotility 2

• Perform nutritional assessment including BMI, weight change over 2 weeks, 3 months, and 6 months, as malnutrition itself worsens gut motility 2

Rule Out Secondary Causes

• Screen for hypothyroidism, diabetes, and celiac disease, as these commonly cause secondary dysmotility and are treatable 3, 2

• Evaluate psychosocial factors that may amplify symptom perception, as psychiatric patients often have higher pain thresholds and may under-report symptoms until complications develop 2, 4

Treatment Algorithm Based on Primary Symptom

For Constipation-Predominant Symptoms:

• Start prucalopride (a selective 5-HT4 agonist) as first-line prokinetic, as it does not affect QT interval and is effective for constipation without the cardiac risks of older agents like cisapride 2

• Consider pyridostigmine using a stepped dosing regimen for refractory constipation, as it has been shown effective even in diabetic patients and is well-tolerated 2

• Avoid long-term domperidone due to QTc prolongation risk, and never use metoclopramide long-term due to irreversible tardive dyskinesia risk 2, 3

For Abdominal Pain:

• Use antispasmodics (hyoscine butylbromide, dicycloverine, or peppermint oil) as first-line, recognizing the paradox that anticholinergics treat pain but may worsen motility 5, 3

• Consider neuropathic agents or antidepressants for persistent pain, but avoid adding medications with additional anticholinergic burden 5

• Never use opioids, as they cause narcotic bowel syndrome and severely worsen dysmotility 5, 2

For Nausea/Vomiting:

• Use ondansetron (5-HT3 antagonist) for refractory nausea, as it does not worsen motility like anticholinergic antiemetics 3

• Consider erythromycin 900 mg/day as a motilin agonist if absent or impaired migrating motor complexes are suspected, though tachyphylaxis limits long-term use 2

• Try octreotide 50-100 μg subcutaneously once or twice daily for severe refractory symptoms, as effects appear within 48 hours and can be maintained long-term, particularly when other treatments fail 2

Critical Medications to Avoid

• Never combine lurasidone with cyclizine or other anticholinergic antiemetics, as this dramatically worsens dysmotility through additive anticholinergic effects 2, 3

• Avoid calcium channel blockers if possible, as they alter colonic motility and worsen pseudo-obstruction 1

• Do not use metoclopramide long-term due to permanent tardive dyskinesia risk, especially problematic in patients already on antipsychotics 2, 3

When Conservative Measures Fail

• Consider naloxone 1.6 mg subcutaneously daily or methylnaltrexone on alternate days to block endogenous opioid effects on motility, even in patients not taking exogenous opioids 2

• Refer to gastroenterology for physiologic testing (gastric emptying scintigraphy, manometry) when symptoms are severe or refractory to first-line treatments 3

• Provide nutritional support with oral supplements first, progressing to nasojejunal feeding if oral intake is inadequate, then parenteral nutrition only if jejunal feeding fails 3

Monitoring and Follow-Up

• Reassess regularly and treat the predominant symptom, as the clinical picture may change over time 2

• Monitor for serious complications including ileus, ischemic bowel, perforation, aspiration pneumonia, and septicemia, which can be life-threatening if constipation is left untreated, particularly with antipsychotic medications 4

• Use objective examinations rather than relying solely on patient reporting, as psychiatric patients often under-report gastrointestinal symptoms due to higher pain thresholds and lack of symptom awareness 4