Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (Investigational Adjunct)

Investigational adjunct for ME/CFS symptom management; pacing strategies, post-exertional malaise avoidance, and individualized supportive care remain primary; graded exercise therapy is no longer recommended per updated NICE guidance.

Tier C — InvestigationalInvestigationalLast updated: 2026-05-26 · Reviewed by ASH Editorial Board

Patient Summary

Is this FDA-cleared for this use?: Not FDA-cleared for myalgic encephalomyelitis / chronic fatigue syndrome. FDA cleared medicinal leeches only for venous congestion in microsurgical reconstruction (K040187, June 2004). Use here is Tier C investigational.
What evidence exists?: Tier C (investigational). No controlled trials. Evidence-based management of ME/CFS centers on pacing — patients learn to operate within their energy envelope to avoid post-exertional malaise. Symptomatic management includes treatment of orthostatic intolerance (salt, fluids, compression, fludrocortisone, midodrine), sleep management, low-dose tricyclics or duloxetine for pain, and treatment of comorbidities. Graded exercise therapy is no longer recommended due to post-exertional malaise risk.
Main risks: Bleeding from each bite site for 6 to 10 hours after the leech detaches
Iron-deficiency anemia from cumulative blood loss across multiple sessions
Aeromonas hydrophila wound infection from leech gut bacteria (uncommon outside reconstructive surgery, but possible)
Allergic reaction to leech saliva (rare; ranges from local itching to anaphylaxis)
Permanent Y-shaped bite-mark scars or hyperpigmentation at attachment sites
Local pain, bruising, swelling, or itching for 1 to 3 days after each session
Post-exertional malaise triggered by treatment sessions, with crash lasting days to weeks
Orthostatic intolerance worsened by blood volume reduction
Significant time and resource expenditure without proven benefit
Who should not consider this: Patients with severe ME/CFS who cannot tolerate the cumulative exertion of multiple sessions
Patients with significant orthostatic intolerance (sessions may worsen it)
Patients who have not addressed pacing, sleep, orthostatic intolerance, and comorbidities
Anyone on blood thinners such as warfarin, apixaban, rivaroxaban, dabigatran, heparin, or daily aspirin used for medical reasons
People with hemophilia or any other inherited bleeding disorder
Patients with severe anemia (hemoglobin under 10 g/dL)
People with an active infection at the planned application site
What to ask your clinician: Has my diagnosis met established ME/CFS criteria (IOM, CCC, or ICC)?
Has orthostatic intolerance been worked up and treated?
Have I worked on pacing within my energy envelope?
What is the risk of post-exertional malaise from a session course?
What is the published evidence base for leeches in ME/CFS?
How will success be measured — function, PEM frequency, both?
When to seek urgent care: Bleeding from a bite site that soaks through more than one dressing per hour
Bleeding that continues more than 24 hours after the leech detached
Spreading redness, warmth, swelling, pus, or red streaks around any bite site
Fever over 38.0 C / 100.4 F, chills, or feeling suddenly unwell after a session
Hives, facial or tongue swelling, throat tightness, or any difficulty breathing
Sudden weakness, dizziness, fast heart rate, or fainting (possible severe blood loss)
Severe new orthostatic intolerance, fainting, or chest pain
Severe post-exertional crash that does not resolve within typical time
New neurologic symptoms not explainable by known ME/CFS pattern

What this does NOT mean

It does not mean leech therapy is FDA-cleared for ME/CFS — the only FDA clearance is venous congestion in microsurgical reconstruction (K040187, June 2004).
It does not replace pacing, the foundation of ME/CFS self-management.
It does not address orthostatic intolerance, sleep, or comorbidities.
It risks triggering post-exertional malaise from cumulative session burden.
It does not have controlled-trial evidence and could worsen function.

Safety cross-references

Clinical Profile

Category: other
ICD-10: G93.32, R53.82
Safety tier: high

Evidence Summary

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multi-system illness defined by substantial functional impairment, post-exertional malaise (PEM), unrefreshing sleep, and cognitive dysfunction or orthostatic intolerance. NICE 2021 guidance updated to remove graded exercise therapy and emphasize pacing-with-symptom-contingent activity (the 'energy envelope') and PEM avoidance. There is no cure and no FDA-approved therapy. Symptom-targeted measures include orthostatic-intolerance management, sleep optimization, gentle cognitive support, and management of comorbid conditions. There is overlap with long COVID. No published controlled trials of hirudotherapy exist for ME/CFS. Anecdotal application is anatomic-region-dependent (cervical, hepatic) without mechanistic basis for fatigue improvement. Bleeding-related fatigue and PEM risk are concerns specific to this population.

Treatment specifics

How many leeches, where they are placed, how long a session lasts, and whether to repeat are clinical decisions made by a qualified provider under institutional protocol — not something to self-administer. Discuss the specifics with a clinician experienced in medicinal leech therapy. (Clinicians: switch the audience selector in the top bar to “Clinician” to view protocol detail.)

Contraindications

Active anticoagulant therapy (warfarin INR >2.0, DOACs, heparin)
Hemophilia or other bleeding disorder
Severe anemia (Hb <10 g/dL)
Active bacteremia or sepsis
Known hypersensitivity to leech salivary proteins
Pregnancy (relative — first/third trimester)
Immunocompromised state with severe neutropenia
Severe ME/CFS (bedbound, profound PEM)
Orthostatic intolerance or POTS (cervical placement risk)
Active long COVID with thromboembolic concerns
Mast cell activation syndrome (common ME/CFS comorbidity)
Concurrent moderate-severe anemia
Patient unable to commit to post-procedure pacing

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