Management of Depression, Anxiety, and Insomnia in Hypermobile Ehlers-Danlos Syndrome

Pharmacological Interventions

• The American Gastroenterological Association recommends tricyclic antidepressants, such as amitriptyline, for pain management in hypermobile EDS patients, due to their ability to address neuropathic pain components and psychiatric comorbidities 1
• Low-dose sedating antidepressants, including amitriptyline, are guideline-recommended for chronic insomnia when accompanied by comorbid depression, as they provide sleep-promoting effects and pain management benefits 3, 4
• Amitriptyline should be initiated at a low dose (10-25 mg at bedtime) and titrated gradually to 75-100 mg if tolerated for full antidepressant effect, while addressing pain and insomnia in hypermobile EDS patients 2
• Duloxetine is recommended as an SNRI alternative for severe pain with comorbid depression in EDS patients, although it lacks the sleep-promoting effects of amitriptyline 2

Non-Pharmacological Interventions

• The American College of Medical Genetics recommends low-resistance exercise to improve joint stability through increased muscle tone, which provides robust benefits for pain, sleep, fatigue, and daily functioning in hypermobile EDS patients 1
• Cognitive Behavioral Therapy is strongly recommended for chronic pain management in EDS, promoting adaptive behaviors and addressing mood disorders, and should be implemented in conjunction with physical therapy and exercise programs 2
• Cognitive Behavioral Therapy for Insomnia (CBT-I) is the standard first-line treatment for insomnia and should be implemented regardless of pharmacotherapy, as it combines cognitive therapy with behavioral treatments and provides durable benefits beyond treatment completion 3, 5

Screening and Monitoring

• The American College of Medical Genetics recommends screening for Postural Orthostatic Tachycardia Syndrome (POTS) by measuring postural vital signs with an active stand test, and if confirmed, increasing fluid intake and using compression garments 1, 7
• Regular follow-up with a multidisciplinary team, including pain management, physical therapy, psychology/psychiatry, gastroenterology, and cardiology specialists, is required for all hypermobile EDS patients to assess effectiveness, side effects, and need for ongoing medication 1, 7

Medication to Avoid

• The American Gastroenterological Association explicitly recommends avoiding opioids for abdominal or chronic pain in EDS, as they worsen gastrointestinal symptoms, increase complications, and can mimic or exacerbate dysmotility 1, 6
• NSAIDs should not be prescribed as they worsen gastrointestinal symptoms in EDS, and dietary interventions should include nutritional counseling to prevent restrictive eating patterns and avoidant/restrictive food intake disorder (ARFID) 2, 6, 7