What are the options if a medication causes abdominal pain?

Management of Medication-Induced Abdominal Pain

If a medication causes abdominal pain, the primary approach is to discontinue or switch the offending agent when possible, followed by symptomatic management with antispasmodics or peppermint oil as first-line therapy, and tricyclic antidepressants as second-line treatment if pain persists. 1

Immediate Assessment and Drug Discontinuation

• Identify and stop the causative medication if clinically feasible, particularly NSAIDs (which cause ulcers and bleeding in the stomach and intestines), opioids (which should be avoided for chronic abdominal pain management), and other common culprits 2, 3
• NSAIDs can cause gastrointestinal symptoms including stomach pain, constipation, diarrhea, heartburn, and nausea at any time during treatment, and these effects increase with longer use 2
• Opioid medications are commonly misused for chronic abdominal pain but lack clinical evidence supporting long-term efficacy and carry significant risks including constipation, nausea, and potential for abuse 3

First-Line Symptomatic Treatment

For medication-induced abdominal pain that persists after drug discontinuation or when the causative agent cannot be stopped, initiate antispasmodic therapy or peppermint oil as first-line treatment. 1

• Antispasmodics as a drug class ranked second for relief of abdominal pain in network meta-analyses, performing similarly to tricyclic antidepressants 1
• Peppermint oil ranked third for abdominal pain relief and is well-tolerated 1
• These agents work through different mechanisms: anticholinergics inhibit GI smooth muscle contraction, calcium channel inhibitors block calcium transport, and direct smooth muscle relaxants inhibit sodium and calcium transport 4

Common Pitfalls

• Antispasmodics available in North America (dicyclomine, hyoscine, hyoscyamine) vary dramatically in efficacy and safety, so each should be considered individually rather than prescribed as a broad class 4
• Anticholinergic side effects (dry mouth, visual disturbance, dizziness) are common with these agents 1

Second-Line Treatment: Gut-Brain Neuromodulators

If first-line therapy fails, tricyclic antidepressants (TCAs) are the preferred second-line treatment for persistent abdominal pain. 1, 5

TCA Prescribing Algorithm

• Start with 10 mg at bedtime (amitriptyline or nortriptyline) 1, 5
• Titrate by 10 mg weekly or every 2 weeks based on response and tolerability 5
• Target dose is 30-50 mg once daily at night 1, 5
• Secondary amine TCAs (nortriptyline, desipramine) are preferred over tertiary amines (amitriptyline, imipramine) to minimize anticholinergic effects 5

Rationale for TCAs

• TCAs ranked first for relief of abdominal pain in network meta-analyses examining therapies across all IBS subtypes 1
• They reduce abdominal pain with a relative risk of 0.53 (95% CI 0.34-0.83) 5
• TCAs work through the gut-brain axis by modulating norepinephric, serotonergic, and dopaminergic neurotransmitters that affect gut motor function and visceral sensation 1
• Careful explanation of the rationale for their use is required, as patients may be confused about using an "antidepressant" for pain 1

Side Effect Management

• Common TCA side effects include sedation, dry mouth, dry eyes, and constipation, which are dose-dependent 1, 5
• These can be minimized by starting at low doses and titrating slowly 5

Alternative Second-Line Options

If TCAs are not tolerated or contraindicated, serotonin-norepinephrine reuptake inhibitors (SNRIs) are reasonable alternatives. 5

• Start duloxetine 30 mg once daily, titrating to 60 mg based on response 5
• SNRIs have norepinephric effects that provide greater analgesic benefit than SSRIs, which act solely on serotonin receptors and have the least analgesic effect 1
• SNRI side effects include sedation, dry mouth, constipation or diarrhea, anxiety, reduced appetite, nausea, headache, and fatigue 5

Important Caveat

• Avoid SSRIs as monotherapy for medication-induced abdominal pain, as the 2014 AGA guideline suggested against their use for IBS, and they have limited analgesic efficacy 1

Severe or Refractory Cases

For pain that persists despite the above measures:

• Consider combination gut-brain neuromodulators (termed augmentation), such as duloxetine plus gabapentin, which may be more efficacious than monotherapy 1
• Exercise vigilance for serotonin syndrome when combining agents, especially SSRIs and SNRIs together (symptoms include fever, hyperreflexia, tremor, sweating, and diarrhea) 1
• Referral to a multidisciplinary chronic pain team should be considered if pain becomes centrally-mediated 1
• Avoid iatrogenic harms from opioid prescribing, as conventional analgesia including opiates is not a successful strategy for chronic abdominal pain 1