What are the best medications and/or supplements to treat chronic pain in a patient with Hypermobile Ehlers-Danlos Syndrome (hEDS)?

Pain Management in Hypermobile Ehlers-Danlos Syndrome

Start with neuromodulators (gabapentin, tricyclic antidepressants, or SNRIs) as first-line pharmacologic therapy, combined with physical therapy and avoid opioids entirely for chronic pain management. 1

First-Line Pharmacologic Approach

Neuromodulators (Primary Recommendation)

• Gabapentin should be initiated first, titrating to 2400 mg daily in divided doses for neuropathic pain components 2, 1
• Tricyclic antidepressants (particularly amitriptyline) are recommended by the American Gastroenterological Association, starting at low doses (10 mg) and gradually titrating to 75-100 mg if tolerated 2, 1
• SNRIs (serotonin-norepinephrine reuptake inhibitors) are also recommended as neuromodulator options for pain management 1
• Pregabalin can be considered as an alternative to gabapentin, dosed at 75-300 mg every 12 hours 2, 1

Antispasmodics for Abdominal Pain

• Hyoscyamine, dicyclomine, or peppermint oil should be used specifically for abdominal pain components 1

Critical Medication to AVOID

Opioids must be avoided specifically for abdominal or chronic pain in hEDS patients, as explicitly recommended by the American Gastroenterological Association 1. This is a crucial pitfall to avoid, as opioid use is widespread (70-92% reported usage) but contributes to dysmotility and worsens outcomes in this population 3.

Supplement Recommendations

Vitamin C

• Vitamin C supplementation is recommended as it serves as a cofactor for cross-linking of collagen fibrils, potentially improving hypermobility 1

Bone Health Supplements

• Calcium and vitamin D supplementation should be encouraged for all hEDS patients 1

Non-Pharmacologic Therapies (Essential Components)

Physical Therapy (Cornerstone of Treatment)

• Low-resistance exercise to improve joint stability by increasing muscle tone is recommended by the American College of Medical Genetics 1
• Myofascial release techniques are often necessary to facilitate participation in exercise programs 1, 4
• Physical therapy should be prioritized over surgical interventions, which have decreased stabilization and pain reduction outcomes in hEDS compared to non-EDS patients 1

Cognitive Behavioral Therapy

• CBT is strongly recommended for chronic pain management, promoting patient acceptance of responsibility for change and development of adaptive behaviors 2

Additional Modalities

• Yoga is recommended for chronic neck/back pain, headache, and general musculoskeletal pain 2
• Trigger point injections, peripheral nerve blocks, and radiofrequency ablation may be considered as interventional options 4
• Low-dose naltrexone and laser therapy have shown promising effects for decreasing pain and increasing quality of life 5

Pain Management Specialist Referral

A pain management specialist is crucial for patients with chronic pain in hEDS, as stated by the American College of Medical Genetics 1. Given the multifactorial nature of pain in hEDS (musculoskeletal, neuropathic, fibromyalgia-like, and abdominal), specialized expertise is essential 4, 6.

Associated Conditions Requiring Treatment

Mast Cell Activation Syndrome (MCAS)

• When MCAS is suspected, treat with histamine receptor antagonists and/or mast cell stabilizers 1
• Advise patients to avoid triggers including certain foods, alcohol, strong smells, temperature changes, and specific medications 1

Postural Orthostatic Tachycardia Syndrome (POTS)

• Increase fluid and salt intake, implement exercise training, and use compression garments 1
• Consider pharmacological treatments for volume expansion, heart rate control, and vasoconstriction for non-responders 1

Gastrointestinal Symptoms

• Proton pump inhibitors, H-2 blockers, and sucralfate for gastritis and reflux 1
• Promotility agents for delayed gastric emptying 1
• Consider testing for celiac disease as risk is elevated in this population 1

Common Pitfalls to Avoid

• Never prescribe NSAIDs as they can worsen gastrointestinal symptoms and are generally contraindicated 2
• Avoid delaying diagnosis as diagnostic delay increases the likelihood of severe pain 7
• Do not rush to surgical interventions as outcomes are poorer in hEDS patients compared to those without EDS 1
• Paracetamol (acetaminophen) appears safe and can be used for pain management 2