Key Information
Pyridostigmine has a plausible mechanism for transiently enhancing neuromuscular transmission in early stage ALS, where NMJ transmission is impaired but motor neuron numbers are preserved. However, there is no plausible mechanism for slowing ALS progression. Case reports showed PALS without typical MG symptoms did not respond to pyridostigmine. Thus far, clinical trials of pyridostigmine in PALS have not been conducted. Two small clinical trials of other cholinesterase inhibitors failed to show efficacy in PALS.Additionally, pyridostigmine carries potential,albeit mild, risks, including gastrointestinal side effects and excessive salivation at recommended doses. Given the lack of mechanistic plausibility and efficacy in case reports, we do not support the use of pyridostigmine as a pharmacological agent for slowing ALS progression.
Mechanistic plausibility
Mechanistic plausibility
Mechanistic plausibility - C
Mechanistic plausibility
Mechanistic plausibility
Mechanistic plausibility
Pre-clinical models (animal or cell models recognized by ALSUntangled reviewers to be relevant to ALS)
Grade A: Two or more peer-reviewed publications reporting benefits in well-designed studies.
Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.
Pre-clinical models (animal or cell models recognized by ALSUntangled reviewers to be relevant to ALS)
Grade B: One peer-reviewed publication reporting benefits in a well-designed study.
Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.
Pre-clinical models (animal or cell models recognized by ALSUntangled reviewers to be relevant to ALS)
Grade C: One or more peer-reviewed publication(s) reporting benefits in flawed studies.
Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.
Pre-clinical models (animal or cell models recognized by ALSUntangled reviewers to be relevant to ALS)
Pre-clinical models (animal or cell models recognized by ALSUntangled reviewers to be relevant to ALS)
Pre-clinical models (animal or cell models recognized by ALSUntangled reviewers to be relevant to ALS)
Patient case reports
Patient case reports
Patient case reports
Patient case reports
Patient case reports
Patient case reports
Patient trials
Patient trials
Patient trials
Grade D: One or more peer-reviewed publications reporting benefits in a flawed trial.
Flawed trials means those in which there are identifiable problems with patient selection, randomization, blinding, controls or follow-up. These have ‘high or unclear risk of bias’ according to published criteria. Well-designed trials are those that have ‘low risk of bias’.
Patient trials
Patient trials
Risks (harms that occurred on this treatment)
Risks (harms that occurred on this treatment)
Risks (harms that occurred on this treatment)
Grade B (oral): More than 0% but less than10% of exposed patients experienced harms (no hospitalizations or deaths)
Grade D (intravenous): More than 0% but less than 5% of exposed patients experienced death or hospitalizations
Risks (harms that occurred on this treatment)
Risks (harms that occurred on this treatment)
Risks (harms that occurred on this treatment)
Grade D: More than 0% but less than 5% of exposed patients experienced death or hospitalizations
Grade F: At least 5% of exposed patients experienced death or hospitalization