A recent study published in JAMA Network Open reveals a notable association between the use of common psychiatric medications and both the risk and progression of amyotrophic lateral sclerosis (ALS). Conducted using Swedish nationwide registry data, the study examined over 1,000 ALS patients and matched controls, including siblings and spouses, to assess whether prior prescriptions for anxiolytics, hypnotics and sedatives, or antidepressants correlated with ALS onset or influenced its clinical course. The findings indicate that individuals with a history of psychiatric medication use had a significantly higher risk of developing ALS—even when prescriptions were recorded more than five years prior to diagnosis. Specifically, the study found a 34% increased risk associated with anxiolytics, 21% with hypnotics and sedatives, and 26% with antidepressants. These associations persisted after adjusting for socioeconomic, demographic, and psychiatric history variables, and were especially pronounced in patients under the age of 65.

Importantly, prediagnostic use of psychiatric medications also appeared to predict worse outcomes after ALS diagnosis. Patients with prior use of anxiolytics or antidepressants experienced higher mortality and faster decline in functional status, as measured by the ALS Functional Rating Scale–Revised (ALSFRS-R). Although the reasons remain uncertain, these findings suggest that psychiatric symptoms may reflect early, prodromal manifestations of ALS or that there are shared neurobiological pathways linking psychiatric disorders with motor neuron degeneration.

While the study cannot establish causality, it adds to growing evidence that psychiatric symptoms—especially depression, anxiety, and sleep disturbances—may be early indicators of neurodegenerative disease. The possibility of shared genetic risk, such as variants affecting synaptic or neuroimmune pathways, further supports this connection. Clinicians should consider the broader neurological context when evaluating persistent psychiatric symptoms, particularly in middle-aged patients.

In conclusion, this study reinforces the clinical importance of psychiatric histories in assessing future neurodegenerative risk. For practicing clinicians, it suggests that prior psychiatric medication use may not only signal mental health challenges but could also warrant closer neurological observation, particularly in patients with other subtle symptoms suggestive of ALS or related conditions. Early recognition may ultimately improve diagnostic accuracy and guide more proactive care strategies.

Reference:
Chourpiliadis C et al. JAMA Netw Open. 2025; 8(6):e2514437. Abstract.