Treatment Database

An acetylcholinesterase inhibitor that boosts acetylcholine signaling, including at autonomic ganglia, strengthening the reflexes that regulate heart rate and blood pressure. It is used off-label for POTS and orthostatic intolerance and has been studied for exercise intolerance in ME/CFS. In a randomized, placebo-controlled crossover trial in POTS (Raj et al., Circulation 2005; n=17), a single 30 mg dose lowered standing heart rate at 2 hours (100 vs. 111 bpm on placebo) and reduced symptom burden. Longer-term use is supported mainly by a retrospective single-center series (Kanjwal et al., Pacing and Clinical Electrophysiology 2011). In ME/CFS, a randomized placebo-controlled trial (Chest 2022; n=45) found that a single 60 mg dose prevented the fall in peak oxygen uptake and cardiac output seen with placebo on repeat invasive exercise testing; longer-term effects have been reported only in a non-randomized conference abstract (Squires et al., ERS 2023), in which 37 people who took it for about 2 years improved on exercise-test measures while 16 untreated people did not. In fibromyalgia, a 6-month randomized trial of pyridostigmine with or without exercise (Jones et al., Arthritis Rheum 2008; n=165) found it did not improve pain or most symptoms, though sleep and anxiety improved. In the TREATME patient survey, Mestinon was among the treatments most often reported to improve POTS symptoms. The LIFT trial (NCT06366724) is testing 13 weeks of pyridostigmine, with or without low-dose naltrexone, in ME/CFS and Long COVID with orthostatic intolerance. A 2025 systematic review of POTS trials names pyridostigmine among mainstay treatments but calls for larger randomized trials. It is contraindicated with mechanical bowel or urinary obstruction and needs caution in asthma.