Mestinon (pyridostigmine) has been used to treat postural tachycardia syndrome (POTS) and may improve symptoms such as a fast heart rate (tachycardia) and symptom burden (Raj et al., 2005). However, research that investigated the addition of Mestinon to standard beta-blocker treatment (propranolol or bisoprolol) found no additional advantage with the addition of Mestinon and suggested beta-blocker therapy alone to be the preferred option (Moon et al., 2018). Diarrhea is a common side effect of Mestinon that may limit its use for extended periods. The use of Mestinon for POTS is off-label (not an FDA-approved use).

Mestinon works by preventing the breakdown of acetylcholine, a nerve transmitter. A disturbance in the transmission of acetylcholine between ganglia is thought to cause the imbalance of the autonomic nervous system in POTS. Pyridostigmine increases parasympathetic nervous system activity and decreases heart rate in POTS. For more information about POTS see here.

Raj et al., 2005 performed a randomized crossover trial on 17 patients with POTS assigning them pyridostigmine (Mestinon) 30 mg orally and a placebo, on separate mornings. The patients’ heart rates were significantly lower 2 hours after pyridostigmine than after placebo (100+/-16 versus 111+/-14 bpm, P=0.001) and pyridostigmine significantly decreased the standing heart rate from baseline at 2 and 4 hours, and symptom burden at 4 hours. Blood pressure did not significantly change.

Moon et al., (2018) randomly assigned 103 POTS patients to one of 4 medical treatments (Group 1: propranolol; Group 2: bisoprolol; Group 3: propranolol+pyridostigmine (Mestinon); and Group 4: bisoprolol+pyridostigmine) for 3 months. Pyridostigmine was prescribed at a dose of 30 mg twice a day, which was maintained for 3 months. All treatments significantly improved orthostatic intolerance symptoms, symptoms of depression, and improved quality of life. Propranolol and bisoprolol demonstrated comparable therapeutic effects for POTS patients but additional pyridostigmine administration did not offer any additional benefits.