Rapid Eye Movement Sleep Suppressing Antidepressant Prescription is Associated with Improved Survival in Amyotrophic Lateral Sclerosis.

Authors

Cosmo Fowler, David C Kaelber, Donald L Bliwise, Meredith K Greer

Published in

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. Volume 47. Issue 8. Jun 21, 2026. Epub Jun 21, 2026.

Abstract

Rapid eye movement (REM) sleep is a period of physiological vulnerability for patients with neuromuscular disease, owing to a generalized loss of muscle tone that spares only the diaphragm. Several antidepressants have been observed to reduce REM sleep fraction on polysomnography. We investigated whether prescription of REM-suppressing antidepressants (RSAs) versus non-REM-suppressing antidepressants (NRSAs) is associated with differential survival in patients with amyotrophic lateral sclerosis (ALS).
Using the U.S. Collaborative Network of the TriNetX Analytics platform, we compared 1-year mortality in ALS patients prescribed RSAs or NRSAs within 3 months of diagnosis, identified by ICD-10-CM-coded encounter diagnoses with riluzole prescription between May 2014 and May 2024. We used Cox proportional hazards models, Kaplan-Meier analysis, and risk difference analysis, with and without propensity score matching (PSM).
Among 14,441 patients with ALS and riluzole prescription, 5,057 were prescribed either RSAs (N = 4,177) or NRSAs (N = 880). The NRSA cohort had a higher risk of death (HR 1.28, 95% CI 1.11 - 1.46), with 1-year survival of 60.73% versus 68.61% for RSAs (log-rank p<0.001). After PSM, the difference narrowed and was borderline by log-rank test (60.97% vs 65.92%, p=0.035), while the risk-difference analysis was no longer significant (RR 1.07, 95% CI 0.92 - 1.25), indicating an attenuated and statistically fragile association.
RSA prescription was associated with modestly better survival, but this association weakened markedly after matching and cannot establish causation; residual confounding, particularly by indication, cannot be excluded. These findings are hypothesis-generating, and prospective studies incorporating polysomnography and ALS-specific prognostic factors are needed.

PMID:
42472717
Bibliographic data and abstract were imported from PubMed on 20 Jul 2026.

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