Common Psychiatric Meds Tied to Increased ALS Risk

TOPLINE:

Prescribed use of anxiolytics, hypnotics and sedatives, or antidepressants was associated with a significantly increased risk for future development of amyotrophic lateral sclerosis (ALS) and a worse prognosis after diagnosis compared to nonuse, a large case-control study showed.

METHODOLOGY:

• This nested case-control study included data from the Swedish Motor Neuron Disease Quality Registry for more than 1000 patients with ALS (mean age at index date, 67.5 years; 53% men) diagnosed between 2015 and 2023. The patients were matched for age and sex with more than 5000 population control individuals.
• Researchers examined the prescribed use, defined as having at least two prescriptions of psychiatric medications prior to ALS diagnosis, including anxiolytics, hypnotics and sedatives, and antidepressants.
• Disease progression rate was calculated at diagnosis, and functional decline was calculated at diagnosis and over a median follow-up duration of 1.3 years using ALS Functional Rating Scale-Revised (ALSFRS-R) scores.
• Covariates included age, sex, socioeconomic status, country of birth, and educational level.

TAKEAWAY:

• After adjusting for covariates, the prescribed use of psychiatric medications overall was significantly associated with increased risk for ALS across all time windows before diagnosis. Odds ratios (ORs) for ALS among individuals prescribed hypnotics and sedatives 0-1 years before diagnosis, those prescribed anxiolytics 1-5 years before diagnosis, and those prescribed antidepressants more than 5 years before diagnosis were 6.1, 1.6, and 1.2, respectively.
• After excluding the year before ALS diagnosis, use of antidepressants (OR, 1.3), anxiolytics (OR, 1.3), or hypnotics and sedatives (OR, 1.2) was still linked to increased ALS risk.
• Compared with nonuse, use of anxiolytics (adjusted hazard ratio [HR], 1.5) or antidepressants (HR, 1.72) before ALS diagnosis was associated with shorter survival in patients with ALS.
• After multiple adjustments, patients with ALS who used antidepressants before diagnosis had significantly lower ALSFRS-R scores at diagnosis and a faster rate of functional decline (β = -2.5).

IN PRACTICE:

“These findings suggest a potential link between psychiatric medications, or their indications (ie, psychiatric disorders), and the risk and progression of ALS,” the investigators wrote.

Still, Ammar Al-Chalabi, PhD, professor of neurology and complex disease genetics, King’s College London, London, England, said in a statement from the Science Media Centre that the associated effect on disease risk was small “except in the year immediately before diagnosis,” when there are already symptoms of motor neuron disease.

“At most it represents a 25% increase in relative risk, which for a condition with a 1 in 300 lifetime risk, is not a big change,” added Al-Chalabi, who was not involved with the research.

SOURCE:

This study was led by Charilaos Chourpiliadis, MD, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. It was published online on June 04 in JAMA Network Open.

LIMITATIONS:

Psychiatric medications were prescribed for overlapping conditions, limiting indication specificity. Exposure misclassification was possible because of the lack of data on continuous use after the first prescription, and potential risks for overmatching in relative comparisons and residual confounding existed. Additionally, genetic data, including the statusof the C9orf72 variant, were incomplete and may have affected the findings’ generalizability. The analyses of ALS progression may have also lacked generalizability because they were restricted to regions with complete clinical data.

DISCLOSURES:

The study was funded by the European Research Council Starting Grant, CDC, and Swedish Research Council. Two of the seven investigators reported having consulting and other roles with or receiving grant support from various pharmaceutical companies and research organizations outside the submitted work. Full details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.