By Lucy Piper, medwireNews Reporter
medwireNews: Treatment with common psychiatric medications may be associated with an increased risk of amyotrophic lateral sclerosis (ALS), suggests a case-control study published in JAMA Network Open.
“Furthermore, we demonstrated shorter survival and faster functional decline among patients with ALS who had prediagnostic use of psychiatric medications, especially antidepressants, compared with patients without such experience”, say Charilaos Chourpiliadis (Karolinska Institute, Stockholm, Sweden) and colleagues.
They note that “although ALS has been long considered a disease affecting only the motor neurons, it is increasingly recognized that patients with ALS manifest psychiatric symptoms.”
The team used nationwide health and population registers in Sweden to compare the prior use of at least two prescriptions of anxiolytics, hypnotics, sedatives, or antidepressants among 1057 people with ALS and 5281 individuals without ALS.
The participants were aged a mean of 67.5 years, 53.1% were men, and the ALS patients had a mean Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFR–R) score of 36.1 points out of a possible 48 points, where higher scores indicate better function.
The results showed that having at least two prescriptions of the psychiatric medications more than a year prior significantly increased the risk for ALS by 34% in the case of anxiolytics, 21% with the use of hypnotics or sedatives, and 26% with antidepressants.
This increased risk for ALS with prior use of psychiatric medications was seen at all time points prior to diagnosis, namely 0–1 years, 1–5 years and more than 5 years, and was consistent across men and women.
However, the association was restricted to people younger than 65 years old, which the investigators say “may be attributed to surveillance bias, health-seeking behaviors, and other factors.” They suggest that “[c]loser monitoring in younger patients with psychiatric symptoms might lead to an earlier ALS diagnosis.”
When the patients with ALS were compared with their siblings or spouses without the condition, to allow for the potential effects of familial confounding, the odds ratios for ALS were all numerically increased with the prior use of psychiatric medications, but only significantly so for anxiolytics among siblings (OR=1.41) and antidepressants among spouses (OR=1.35).
During a median 1.33 years after diagnosis, 1024 of the patients with ALS died or initiated invasive ventilation, and Chourpiliadis and team found that prediagnostic use of anxiolytics or antidepressants was associated with a significant 52% and 72% increased risk of death, respectively, after taking into account confounding factors, such as age, sex, disease progression rate, BMI, ALSFR–R score and diagnostic delay.
Prediagnostic use of antidepressants, specifically, was also associated with a significantly faster decline in ALSFR–R score over time in the ALS patients, after multivariable adjustment.
The study authors propose that “increased ALS risk associated with psychiatric medication use more than 5 years before diagnosis might indicate that psychiatric symptoms are prodromal symptoms of ALS as of other neurodegenerative disorders.”
They add that “further studies are needed to differentiate the effect of psychiatric medications from the effect of their indications (ie, underlying psychiatric disorders) on the risk of ALS development.”
News stories are provided by medwireNews, which is an independent medical news service provided by Springer Healthcare Ltd. © 2025 Springer Healthcare Ltd, part of Springer Nature
JAMA Netw Open 2025; 8: e2514437
https://pubmed.ncbi.nlm.nih.gov/40465292
Keywords: amyotrophic lateral sclerosis, psychiatric medications, anxiolytics, hypnotics, sedatives, antidepressants