Summary
Pyridostigmine is tracked by OSMF as an investigational option for ME/CFS; no regulator has approved it for this indication, and most post-viral conditions have no approved disease-modifying therapy at all. ClinicalTrials.gov lists 1 registered trial linking Pyridostigmine to ME/CFS: 1 is currently recruiting. The most advanced is Phase 2 (NCT06366724, sponsored by Brigham and Women's Hospital). It plans or enrolled 160 participants. Registered activity dates to 2024. The literature layer holds 5 publications for this pair: 1 curated reference and 4 PubMed search records. Publication years run from 2004 to 2025. Items here are search-derived or curated references rather than classified trial reports; treat them as leads to read, not as graded evidence.
Myalgic Encephalomyelitis / Chronic Fatigue Syndrome is tracked on the OSMF post-viral programme alongside ME/CFS, Long COVID, POTS and MCAS. Across the programme, 191 candidate agents are logged for ME/CFS, most of them preliminary; this page isolates the record for one of them.
Evidence table
| Evidence tier | C · Preliminary |
|---|---|
| Evidence score | 14.5 (trials 4.0, literature 5.5, tier 5, approved bonus 0.0) |
| Registered trials | 1 total: 1 recruiting, 0 active / not yet recruiting, 0 completed, 0 other |
| Linked publications | 5 (4 PubMed search records, 1 curated reference) |
| Agent type | Other (Other / Unclassified) |
| Development stage (any indication) | Investigational |
| Mechanism / class | Not recorded |
| Data sources | OSMF therapeutic agent database, ClinicalTrials.gov, PubMed |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT06366724 | LIFT: Life Improvement Trial Brigham and Women's Hospital · 2024 | recruiting | Phase 2 | 160 |
Published literature
- Curated reference (PACVS Evidence Map) Beneficial effect on hemodynamics in POTS; particularly relevant for hyperadrenergic phenotype; 21-RCT systematic review (2025)PACVS Evidence Map · 2025
- PubMed record (biomarker-intervention search) Neurovascular Dysregulation and Acute Exercise Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Placebo-Controlled Trial of Pyridostigmine.Chest · 2022 · PMID 35526605
- PubMed record (biomarker-intervention search) Contribution of Impaired Parasympathetic Activity to Right Ventricular Dysfunction and Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.Circulation · 2018 · PMID 29167228
- PubMed record (biomarker-intervention search) Elevated Heart Rate is Associated with Cardiac Denervation in Patients with Heart Failure: A 123-Iodine-MIBG Myocardial Scintigraphy Study.Arquivos brasileiros de cardiologia · 2016 · PMID 27982270
- PubMed record (biomarker-intervention search) Cholinergic stimulation with pyridostigmine protects against exercise induced myocardial ischaemia.Heart (British Cardiac Society) · 2004 · PMID 15367503
Mechanism and notes
No mechanism of action is recorded for this pair in the source databases.
Clinical notes: Crossover RCT + review supports hemodynamic benefit, esp hyperadrenergic POTS. 30-60mg TID. Cholinergic SE dose-limiting. Reasonable targeted option.
Safety: Cholinergic side effects (GI cramping, diarrhea, salivation, sweating, bradycardia). Avoid in asthma, mechanical obstruction. Overdose risk cholinergic crisis.
Dosing in studies: 30–60 mg TID (sometimes 30 mg); titrate; study durations often 4–8 weeks for hemodynamic assessment.
Frequently asked questions
Is Pyridostigmine approved for ME/CFS?
Pyridostigmine is tracked by OSMF as an investigational option for ME/CFS; no regulator has approved it for this indication, and most post-viral conditions have no approved disease-modifying therapy at all. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Pyridostigmine in clinical trials for ME/CFS?
ClinicalTrials.gov lists 1 registered trial linking Pyridostigmine to ME/CFS: 1 is currently recruiting. The most advanced is Phase 2 (NCT06366724, sponsored by Brigham and Women's Hospital). It plans or enrolled 160 participants. Registered activity dates to 2024.
What does the evidence show for Pyridostigmine in ME/CFS?
Trials of Pyridostigmine in ME/CFS are registered but none has completed, so there is no outcome evidence from those studies yet; the record is a signal of research interest. OSMF's existing evidence tier for this pair is C (Preliminary), taken from the OSMF therapeutic agent database, which grades agents by the volume and design of condition-specific evidence rather than by effect size.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-10-07. Page built 2026-10-07.