Myasthenia gravis is a disease in which antibodies directed against acetylcholine receptors block the transmission of nerve impulses to muscles, causing fluctuating muscle weakness and fatiguability. Acetylcholinesterase inhibitors, including pyridostigmine, inhibit the breakdown of acetylcholine, which is the neurotransmitter at the neuromuscular junction. The inhibition of breakdown produced by these drugs increases the availability of acetylcholine to stimulate the acetylcholine receptors and so facilitates muscle activation and contraction.
Only one small randomised controlled cross-over trial relevant to the treatment of myasthenia gravis was identified. It included three participants with ocular myasthenia gravis and seven with generalised myasthenia gravis, who received intranasal neostigmine (an acetylcholinesterase inhibitor) or placebo. Symptoms of myasthenia gravis (measured as improvement in at least one muscle function) improved in nine of the 10 participants after the two-week neostigmine treatment phase. No participant improved after the placebo phase (risk ratio 19.00, 95% confidence interval 1.25 to 287.92). Lack of detail in the report meant that the risk of bias was unclear. Adverse events were minor. This is the first update of the review and no further studies were identified.
Several observational studies, case reports, case series and the daily clinical experience favour the use of acetylcholinesterase inhibitors. Consequently, placebo-controlled trials to confirm the effectiveness of the drug are probably not ethical and are unlikely to be performed. At present, the optimal dose and duration of treatment with acetylcholinesterase inhibitors is determined by the balance between clinical improvement and adverse effects. This varies over time and depends on other types of treatment that are given at the same time to inhibit the underlying autoimmune response.