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Treatments

This section summarizes proposed and studied treatments for ME/CFS, their mechanisms of action, and current evidence status. These summaries are for research and educational purposes only and do not constitute medical advice.

πŸ’Š Current & Investigational Treatments

Low-Dose Naltrexone (LDN)

Investigational / Off-label
Immune modulation, microglial suppression (TLR4 antagonist)

Multiple open-label and mechanistic studies suggest LDN may reduce pain, fatigue, and neuroinflammatory signaling in ME/CFS. Mechanistically, it may calm microglial activation and normalize immune function.

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Low-Dose Aripiprazole (Abilify)

Investigational / Off-label
Dopamine partial agonist; may modulate central fatigue signaling and neuroinflammation.

A 2021 Stanford retrospective series (n=101) reported functional improvements in ~70% of ME/CFS patients at doses 0.25–2 mg/day, with fatigue and cognitive symptoms most responsive. Controlled trials are planned.

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Pyridostigmine (Mestinon)

Off-label
Acetylcholinesterase inhibitor; enhances parasympathetic tone and reduces orthostatic intolerance.

Randomized and open-label trials show improved orthostatic tolerance, exercise capacity, and reduced post-exertional symptoms in ME/CFS and POTS subsets.

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Midodrine

Off-label
Peripheral Ξ±-adrenergic agonist; increases venous return and cerebral perfusion in orthostatic intolerance.

Used clinically for POTS and orthostatic hypotension; controlled studies demonstrate improved orthostatic tolerance and symptom reduction in subsets relevant to ME/CFS.

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Fludrocortisone (Florinef)

Off-label
Synthetic mineralocorticoid; expands plasma volume and improves cerebral blood flow.

Common first-line therapy for orthostatic intolerance; a controlled trial in ME/CFS showed modest benefit but high interindividual variability. Often used with salt and fluids.

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Antivirals (Valganciclovir, Famciclovir)

Investigational
Target viral reactivation (EBV, HHV-6, CMV) implicated in post-infectious ME/CFS.

Controlled trials show mixed results: Montoya et al. reported improvement in patients with high herpesvirus titers; others found minimal change. Still under investigation.

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Ampligen (Rintatolimod)

Investigational
Toll-like receptor 3 (TLR3) agonist; modulates innate immunity and RNA antiviral pathways.

Multiple Phase III trials demonstrated modest improvement in exercise tolerance in subsets of ME/CFS patients. Approved for ME/CFS in Argentina; not approved in US/EU.

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Mitochondrial Supplements (CoQ10, NADH, Carnitine, Riboflavin, etc.)

Supportive / Over-the-counter
Support oxidative phosphorylation and reduce oxidative stress; improve cellular energy metabolism.

Randomized trials and meta-analyses show mild improvements in fatigue and quality of life with low risk. Widely used as supportive therapy.

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⚠️ Deprecated / No Longer Recommended

Rituximab

Deprecated
B-cell depletion (anti-CD20 monoclonal antibody).

Initial open-label studies suggested benefit, but large randomized controlled trials failed to show efficacy. The research program was discontinued after the negative phase III trial.

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Cognitive Behavioral Therapy (CBT) & Graded Exercise Therapy (GET)

Deprecated
Behavioral / psychological reconditioning.

Previously recommended by older guidelines; subsequent re-analyses and patient surveys revealed minimal efficacy and potential harm. Removed from NICE guidelines (UK, 2021).

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