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Use of common psychiatric medications (anxiolytics, hypnotics and sedatives, and antidepressants) is linked to a higher risk of developing amyotrophic lateral sclerosis (ALS), and poorer outcomes after diagnosis with shorter survival and faster functional decline, according to a nationwide Swedish study led by Karolinska Institutet

ALS is a fatal neurodegenerative disease traditionally characterized by motor neuron degeneration, though psychiatric symptoms such as depression and anxiety are frequently reported by patients before diagnosis. Previous studies have linked psychiatric disorders to higher ALS risk, but few have directly examined the role of psychiatric medications.

In the study, "Use of Common Psychiatric Medications and Risk and Prognosis of Amyotrophic Lateral Sclerosis, " published in JAMA Network Open, researchers conducted a nationwide register-based case-control and cohort study to examine whether prescribed use of anxiolytics, hypnotics and sedatives, or antidepressants is associated with ALS risk or prognosis.

Data were drawn from Swedish nationwide health and population registers. A total of 1, 057 individuals diagnosed with ALS between 2015 and 2023 were matched by age and sex with 5, 281 ALS-free individuals from the general population. A total of 1, 418 full siblings (709 with ALS) and 871 spouses of patients with ALS were also included as relative controls.

Prediagnostic use of psychiatric medications was associated with an elevated risk of ALS diagnosis. In the population comparison, individuals prescribed anxiolytics had 34% higher odds of ALS, while those prescribed hypnotics and sedatives had a 21% increase, and those prescribed antidepressants had a 26% increase.

After ALS diagnosis, patients with a history of anxiolytic use had a 52% higher hazard of death or invasive ventilation. For antidepressants, the hazard increased by 72%. Hypnotics and sedatives were associated with a 23% higher hazard, though the confidence interval included 1.0 (HR, 1.23; 95% CI, 0.94–1.61).

Functional decline, as measured by ALSFRS-R scores, occurred at a faster rate among patients with prior antidepressant use.

Researchers concluded that use of anxiolytics, hypnotics and sedatives, or antidepressants was associated with a higher future risk of ALS diagnosis. Among patients already diagnosed, prediagnostic use of anxiolytics or antidepressants was also associated with shorter survival and more rapid functional decline.

According to the authors, "These findings suggest a potential link between psychiatric medications, or their indications (i.e., psychiatric disorders), and the risk and progression of ALS, " raising the possibility that psychiatric symptoms may represent early manifestations of ALS or share underlying mechanisms with motor neuron degeneration.

Potential biological links between psychiatric symptoms and ALS pathophysiology such as HPA axis dysregulation, glial activation, or neuroinflammation were noted as areas requiring further study.

Written for you by our author Justin Jackson, edited by Sadie Harley, and fact-checked and reviewed by Robert Egan —this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive. If this reporting matters to you, please consider a donation (especially monthly). You'll get an ad-free account as a thank-you.

More information: Charilaos Chourpiliadis et al, Use of Common Psychiatric Medications and Risk and Prognosis of Amyotrophic Lateral Sclerosis, JAMA Network Open (2025). DOI: 10.1001/jamanetworkopen.2025.14437  Journal information: JAMA Network Open

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