TREATMENT DATABASE

Pyridostigmine (brand: Mestinon) is an acetylcholinesterase inhibitor. Pyridostigmine is poorly absorbed in the gut and does not cross the blood-brain barrier.

Pyridostigmine works by preventing the breakdown of acetylcholine (ACh) in nervous system synapses. This leads to an increase in acetylcholine, a neurotransmitter widely found in both the peripheral and central nervous systems. Acting as both an excitatory and inhibitory neurotransmitter, acetylcholine performs a variety of functions. Within the skeletal muscular system it contracts muscle, allowing for movement. It slows the heart, and promotes REM sleep. In the central nervous system, ACh is closely associated with learning, attention, and short-term memory.

Pyridostigmine is mainly prescribed for myasthenia gravis, an autoimmune condition in which acetylcholine is blocked, leading to profound muscle weakness. In spite of the fact that it does not cross the blood-brain barrier, pyridostigmine is also used to enhance memory in people with Alzheimer's disease. Pyridostigmine has been administered as a treatment for the paralysis caused by organophosphate pesticide poisoning. In a similar vein, the military administered pyridostigmine as a prophylactic to soldiers during the Gulf War to block potential exposure to Soman, a nerve gas which acts on acetylcholine in much the same manner as organophosphate pesticides. Recently, pyridostigmine has been used to treat orthostatic intolerance.

USES IN ME/CFS: In his book, Betrayal by the Brain, Dr. Jay Goldstein proposed that pyridostigmine could be used in ME/CFS with much the same results as in patients with myasthenia gravis, namely the alleviation of muscle weakness. Surprisingly, Dr. Goldstein found that even though pyridostigmine does not cross the blood-brain barrier it increased mental clarity in his ME/CFS patients. He noted that because pyridostigmine helps increase the secretion of growth hormone (GH), it might be of benefit to ME/CFS patients, who tend to have low levels of GH.

In 2003 a group of Japanese researchers published a study in which low-dose pyridostigmine was administered to three ME/CFS patients with dysautonomia and positive Epstein-Barr virus (EBV) titers. In all three cases, a one-month course of pyridostigmine relieved fatigue and muscle weakness. The authors speculated that EBV infection induces antibodies, which, through an inhibition of calcium influx at motor terminals, reduces acetylcholine release and causes muscle weakness and cholinergic autonomic dysfunction. The authors concluded that their case studies “strongly suggest therapy using a small dose (10 mg per day) of oral pyridostigmine in patients with CFS who have had more than a 40% amplitude increase in response to the RNS [repetitive nerve stimulation] test, positive anti-VCA IgG of EBV and mild impairment of autonomic functions.”

Based on findings that pyridostigmine increases growth hormone, a 2008 study of fibromyalgia patients in Portland, Oregon was conducted comparing exercise, diet and treatment with pyridostigmine. While the researchers did not find that either pyridostigmine alone or pyridostigmine plus exercise produced an improvement in most FM symptoms, they did find that pyridostigmine improved anxiety and sleep. The authors speculated that pyridostigmine may have improved vagal tone, thus alleviating sleep and anxiety symptoms.

Treatment rating for Mestinon (pyridostigmine)