Antidepressants that inhibit REM sleep linked to ALS survival: Study
ALS patients susceptible to abnormal breathing patterns during sleep
Antidepressants that suppress the rapid eye movement (REM) stage of sleep are associated with prolonged survival in people with amyotrophic lateral sclerosis (ALS), according to recent research.
Because most muscles are paralyzed during REM, this could increase the risk of breathing issues, including possible respiratory failure, in people with weakened muscles. The findings suggest inhibiting REM sleep may improve outcomes for people with ALS.
“This lends credence to the question of whether pharmacotherapy [medications] to inhibit REM sleep can improve the lives of patients with neuromuscular diseases, ALS in particular, who are prone to sleep-disordered breathing,” Cosmo Fowler, MD, the study’s first author and a sleep medicine fellow at Emory University, said in a press release.
The results were discussed at the American Thoracic Society 2025 International Conference, held recently in San Francisco, in a presentation, titled “Rapid Eye Movement Sleep-Suppressing Antidepressant Use Is Associated With Enhanced Survival in Amyotrophic Lateral Sclerosis.”
Breathing problems may worsen during sleep
ALS is a neurodegenerative disease wherein the specialized nerve cells that control muscle movement are lost, leading to symptoms including progressive muscle weakness.
Among the muscles that can be affected is the diaphragm, which contracts and relaxes to help people breathe in and out. As a result, people with ALS experience breathing problems and may rely more heavily on other surrounding muscles to breathe.
People with weakened respiratory muscles are particularly susceptible to abnormal breathing patterns during sleep, particularly the REM phase of the sleep cycle.
REM is characterized by increased brain activity and is when the most vivid and memorable dreams happen. During REM, most muscle activity is suppressed, essentially paralyzing the body so that a person doesn’t act out their dreams.
This could exacerbate breathing issues for people who rely more on other muscles to breathe, such as those with neuromuscular conditions like ALS. It could lead to disrupted sleep and daytime sleepiness, or in more severe cases, life-threatening complications such as respiratory failure.
Medications to suppress REM sleep, including certain antidepressants, have been shown to ease sleep-disordered breathing in other clinical contexts, including in people with the neuromuscular disease Duchenne muscular dystrophy. This approach hadn’t yet been tested in ALS.
Results showed higher survival rates for REM-suppressed group
To learn more, the scientists looked at electronic health records from people who had been diagnosed with ALS and prescribed the approved therapy riluzole (sold as Tiglutik and generics) between 2003 and 2023, and an antidepressant in the three years before that period.
This included 2,492 people who were prescribed an REM-suppressing antidepressant and 365 who were prescribed an antidepressant not linked to REM suppression.
These findings justify prospective trials of REM-targeted interventions, particularly given the limited treatment options currently available for ALS.
The results showed survival rates after two years were significantly higher in the REM-suppressed group relative to the other group (47.2% vs. 41.1%), amounting to a 21% lower risk of death. After employing a statistical approach to adjust for other influential factors, a similar survival benefit persisted, but this was no longer statistically significant.
“I found it surprising that a clear difference in survival was so readily apparent,” Fowler said. The scientist noted the team had expected to see differences in other short-term outcomes, but anticipated that survival gains would be harder to observe.
“To our knowledge, this is the first study examining differential survival in ALS patients receiving REM-inhibiting versus non-REM-inhibiting antidepressants,” the researchers wrote in the presentation’s abstract, noting the data “aligns with findings from other neuromuscular disorders.”
The findings could offer a new approach to extending survival in ALS, especially considering that respiratory failure is a leading cause of death in this population. Available treatments have a limited impact on survival outcomes.
The analysis was limited by its retrospective nature and use of electronic health records to gather clinical data. Fowler indicated more research, including a clinical trial, will be needed to support the use of REM-suppressing medications for ALS.
“These findings justify prospective trials of REM-targeted interventions, particularly given the limited treatment options currently available for ALS,” the scientists wrote.
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