Antidepressant therapy could increase survival in ALS

Antidepressants that suppress REM (rapid eye movement) sleep appear to improve survival in people with amyotrophic lateral sclerosis (ALS).

Researchers reported the finding on May 21, 2025 at the annual meeting of the American Thoracic Society.

“This lends credence to the question of whether pharmacotherapy to inhibit REM sleep can improve the lives of patients with neuromuscular diseases, ALS in particular, who are prone to sleep disordered breathing,” said first author Cosmo Fowler, MD, a sleep medicine fellow at Emory University in Atlanta.

As background, the authors noted that pharmacological suppression of REM sleep has been found to improve sleep disordered breathing and nocturnal hypoxemia in a variety of patients. “To our knowledge, this approach has not been investigated in amyotrophic lateral sclerosis (ALS), the most common form of motor neuron disease,” they said.

In this new retrospective study, the investigators extracted and analyzed data from a large patient database. The extracted data pertained to ALS patients who had been prescribed antidepressants.

The researchers compared outcomes for those who had been treated with REM-suppressing antidepressants to outcomes for those whose medications did not interact with REM sleep.

The primary outcome was 2-year survival.

The researchers identified 17,444 patients with ALS who met inclusion criteria, 2,492 (14.3%) of whom comprised the REM-inhibited cohort and 365 (2.1%) the non-REM-inhibited cohort.

They noted, “We defined a REM-inhibited cohort in which patients were prescribed one of several antidepressant medications associated with the suppression of REM sleep in the 3 years preceding inclusion criteria, as well as a non-REM-inhibited cohort who received antidepressants not linked to REM suppression, excluding patients who received prescriptions from both classes.”

They found that two-year survival was significantly higher for patients in the REM-suppressed cohort compared to the non-REM inhibited cohort (47.18% vs 41.06%).

Fowler noted that, “The findings are especially significant considering the shortage of treatment options that are effective in altering the course of ALS; current treatments are largely aimed at improving quality of life, not increasing survival.”

The authors concluded, “To our knowledge, this is the first study examining differential survival in ALS patients receiving REM-inhibiting versus non-REM-inhibiting antidepressants. The observed survival benefit aligns with findings from other neuromuscular disorders, where REM sleep suppression ameliorates nocturnal respiratory dysfunction. While our investigation was limited by its retrospective nature and potential confounding factors inherent to EHR [electronic health record) data, the results suggest that pharmacologically targeting a period of known vulnerability in ALS may have meaningful clinical impact. These findings justify prospective trials of REM-targeted interventions, particularly given the limited treatment options currently available for ALS.”