Why Sleep Is So Difficult in EDS, POTS, and MCAS — and What Can Actually Help

By Stephanie Sutherland, BSN, RN

If you live with Ehlers-Danlos Syndrome (EDS), Postural Orthostatic Tachycardia Syndrome (POTS), Mast Cell Activation Syndrome (MCAS), or any combination of the three, chances are you've experienced disrupted sleep. You’re not alone—and you’re definitely not imagining it.

As both a nurse and someone with chronic illness who treats these conditions, and as someone who listens closely to patients, I can confirm this: poor sleep is one of the most pervasive and debilitating symptoms across these diagnoses. Worse, traditional sleep medications often fail to provide relief. In fact, many patients report that despite sleeping for 8–10 hours, they still wake up feeling exhausted, wired, or worse.

Let’s explore why sleep is so disrupted in these conditions, and what solutions—both lifestyle and medical—may help.

Why Is Sleep So Difficult?

1. Hyperarousal of the Nervous System

Pain and sympathetic overdrive are a perfect storm for sleeplessness. Chronic pain in EDS activates the stress response system, making it harder for the brain to transition into deeper stages of sleep. At the same time, autonomic dysregulation in both POTS and MCAS creates a state of “wired but tired,” where your body is exhausted but your nervous system stays stuck in alert mode. This mismatch interferes with sleep onset and sleep maintenance.

2. Circadian Disruption from Dysautonomia

Your autonomic nervous system (ANS) helps regulate circadian rhythms, body temperature, and blood pressure during sleep. In patients with POTS or hypermobile EDS, dysautonomia can blunt the normal nighttime drop in heart rate and blood pressure, leading to fragmented, shallow, and non-restorative sleep (Ferini-Strambi et al., 2021).

3. Nocturnal Mast Cell Activation

In MCAS, nocturnal histamine surges can lead to itching, flushing, tachycardia, or a sensation of restlessness around 2–4 a.m. Histamine is a wake-promoting neurotransmitter, and sudden release during sleep may cause unexplained night wakings, vivid dreams, or nighttime anxiety.

4. Obstructive Sleep Apnea

Many patients with hypermobile EDS have craniofacial abnormalities, airway instability, or lax connective tissue in the throat, predisposing them to obstructive sleep apnea (OSA). Even young, thin individuals may experience significant OSA, leading to nighttime hypoxia and daytime fatigue (Champagne et al., 2024).

5. Idiopathic Hypersomnia & non-restorative Sleep

POTS patients frequently report excessive daytime sleepiness despite a full night's sleep. Some meet criteria for idiopathic hypersomnia, a condition that may reflect disordered sleep architecture due to poor transitions between REM and NREM sleep (Adra et al., 2022).

Why Most Sleep Medications Don't Work

Many standard treatments for insomnia—like benzodiazepines, sedating antihistamines, and melatonin—provide sedation but not necessarily restorative sleep. In dysautonomia and hyperarousal-driven insomnia, these medications may:

• Aggravate postural instability in POTS
• Increase mast cell mediator release (in the case of some antihistamines or SSRIs)
• Leave patients groggy and unrefreshed

Worse still, long-term hypnotics may reduce REM sleep or suppress natural sleep cycles, which are already disrupted in this population.

A More Targeted Pharmacologic Approach: Dayvigo (Lemborexant)

Among the limited pharmacologic options, Dayvigo (lemborexant) has emerged as a promising alternative for patients with dysautonomia-related sleep disturbances. It belongs to a class of drugs called dual orexin receptor antagonists (DORAs), which work differently than traditional sleep medications.

How It Works:

• Orexins are neuropeptides that promote wakefulness.
• In people with hyperaroused nervous systems, orexin levels may be inappropriately elevated.
• Dayvigo selectively blocks the orexin system, helping the brain "disengage" and initiate sleep more naturally.

Why It's Helpful for EDS/POTS/MCAS:

• Non-sedating during the day
• Preserves normal sleep architecture (including REM and deep sleep)
• Doesn't impair blood pressure regulation or worsen POTS symptoms
• May avoid histaminergic effects that can provoke MCAS symptoms

Anecdotally and clinically, patients report improved sleep initiation and sleep maintenance, with less next-day drowsiness compared to older sleep medications.

Additional Strategies That May Help

💤 1. Optimize Sleep Hygiene

These steps still matter, especially when layered with other strategies:

• Stick to a consistent sleep-wake schedule
• Limit screen time 60 minutes before bed
• Keep the bedroom cool, dark, and quiet
• Use a weighted blanket (if tolerated)

🧘 2. Pre-Bed Pain Management

Gentle stretching, Epsom salt baths, TENS units, or low-dose nighttime medications may reduce discomfort that interferes with falling asleep (Levine et al., 2022).

🧦 3. Daytime Compression for POTS

Wearing compression shorts (not leggings) during the day improves blood return, which may reduce adrenaline spikes at night (De Wandele., 2017). Make sure you drink fluids and take a salty snack before bed.

🩺 4. Sleep Study Referral

If you snore, wake with a dry mouth, or have unrefreshing sleep, ask your provider to screen for obstructive sleep apnea—even if you're not the "typical" OSA patient.

🧃 5. Mast Cell Stabilization Before Bed

For MCAS, pre-bed use of:

• H1 and H2 blockers
• Low-histamine diet at dinner
• Mast cell stabilizers such as Ketotifen and cromolyn

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Adra, N., Reddy, M., Attarian, H., & Sahni, A. S. (2022). Autonomic dysfunction in idiopathic hypersomnia: an overlooked association and potential management. Journal of Clinical Sleep Medicine, 18(3), 963–965.

Champagne, K. A., Chapados, D., Barriga, P. C., & Trottier, M. (2024). Still tired after sleeping: Obstructive sleep apnea (OSA) secondary to hypermobile Ehlers-Danlos syndrome (hEDS). In The Symptom-Based Handbook for Ehlers-Danlos Syndromes and Hypermobility Spectrum Disorders (pp. 355–363). Elsevier.

Ferini-Strambi, L., Marelli, S., & Salsone, M. (2021). Primary insomnia and dysautonomia. In Autonomic Nervous System and Sleep: Order and Disorder (pp. 165–171).

De Wandele, I., O’Callaghan, C., Pocinki, A., & Rowe, P. (2017). Chronic fatigue in Ehlers–Danlos syndrome, Hypermobile type. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 175(1), 175–180.

Jansson‐Fröjmark, M., & Boersma, K. (2012). Bidirectionality between pain and insomnia symptoms: a prospective study. British Journal of Health Psychology, 17(2), 420–431.

Levine, D., McDonald, S., Curtis, N., Foster, A., Smiddy, E., & Healy, M. (2022). Sleep Disturbance and Common Interventions Used for Sleep Management in Individuals with Hypermobile Ehlers-Danlos Syndrome. Archives of Physical Medicine and Rehabilitation, 103(12), e95–e96.

Mishima, K., Fujimoto, K., Endo, A., & Ishii, M. (2024). Safety and Efficacy of Lemborexant in Insomnia Patients: Results of a Postmarketing Observational Study of Dayvigo® Tablets. Drugs in R&D, 24(2), 211-226.

Dual Orexin Receptor Antagonist Benefits:

Blair, H. A. (2020). Lemborexant in insomnia disorder: a profile of its use. Drugs & Therapy Perspectives, 36(10), 427-434.

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