Key Information
Melatonin has plausible mechanisms, some positive (and some negative) pre-clinical data, and two case reports in which it was part of a cocktail of treatments associated with recovery of lost motor function. As we have stated previously, there are
multiple possible explanations for cases like these. There was also a very small, flawed retrospective study suggesting that PALS taking it progressed more slowly and lived longer than PALS were not taking it. Melatonin appears safe at high doses, but evidence is lacking for a proven benefit in slowing disease progression in ALS. Furthermore, an optimal dose and route of administration have not been established. Based on this data, a pilot trial of melatonin in PALS would be reasonable, but we cannot yet recommend it as an ALS treatment.
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