Key Information
Click on any letter grade below for more info:
Preclinical Trials Grade:
U
Published: Nov 2025
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.
Grade A: Shown in a peer-reviewed publication to act on a relevant mechanism in humans
Grade B: Shown in a peer-reviewed publication to act on a relevant mechanism in pre-clinical model(s)
Grade C: Theoretically and plausibly acts on an ALS-relevant mechanism in humans
Grade D: Acts on a biological mechanism but it is not clear that this mechanism is relevant in ALS
Grade F: Implausible; would violate known principles or laws of biology
Grade U: No useful information was found for this category
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’.
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’.
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’.
Grade D: One or more non-peer reviewed studies reporting benefits (published on a website or in an abstract)
Grade F: The only studies available show no benefit
Grade U: No useful information was found for this category
Grade A: One or more peer-reviewed publications reporting benefits with validated diagnosis and benefits
Grade B: More than one unpublished report of benefit with validated diagnosis and benefits
Grade C: One unpublished report of benefit with validated diagnosis and benefits
Grade D: Subjective report(s) of benefit without validated diagnoses and/or benefits
Grade F: The only reports available show no benefit
Grade U: No useful information was found for this category
Two or more peer-reviewed publications describing benefits in well-designed randomized, blinded placebo-controlled phase III trials
Grade C: One or more peer-reviewed publications reporting benefits in a well-designed randomized, blinded, placebo-controlled phase I or II trial
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’.
Grade F: The only trials available show no benefit
Grade U: No useful information was found for this category
Grade A: No exposed patients appear to have experienced harms
Grade B: More than 0% but less than 10% of exposed patients experienced harms (no hospitalizations or deaths)
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
Grade C: At least 10% of exposed patients experienced harms (no hospitalizations or deaths)
Grade D: More than 0% but less than 5% of exposed patients experienced death or hospitalizations
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
Grade F: At least 5% of exposed patients experienced death or hospitalization
Grade U: No useful information was found for this category
