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Updated: Mar 28, 2026

Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
Chronotherapy shortens hospitalization for bipolar depression: a single-center replication across three decades
Sara Dallaspezia1, Francesco Attanasio2, Simone Maruca3
1Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Background:
Chronotherapeutic interventions have been proposed as non-pharmacological strategies for the rapid modulation of depressive symptoms in bipolar disorder. Total sleep deprivation (TSD) may induce short-term mood improvements, and morning bright light therapy (BLT) has been suggested to help stabilize these effects. However, the impact of these interventions on service-level outcomes, including length of hospital stay (LOS), has not been systematically evaluated.
Methods:
We analyzed two non-overlapping retrospective cohorts (1994-1998 and 2015-2024) from the same Mood Disorders Unit, including adults hospitalized for a bipolar depressive episode. Within each cohort, patients received either treatment as usual (TAU) or TAU with chronotherapy, consisting of TSD in the earlier cohort and TSD with morning BLT in the later one. LOS was examined with general linear models adjusted for age and sex.
Results:
The combined sample included 1241 admissions (706 from 1994-1998; 535 from 2015-2024). In both cohorts, LOS was shorter with TSD than with TAU (1994-1998: 20.99±11.09 days vs 23.23±13.34, F = 5.31, p = 0.02; 2015-2024: 24.00±8.24 vs 27.62±8.67, F = 15.46, p < 0.01), with a small effect size in the earlier cohort (d = 0.176) and a small-to-moderate effect in the later one (d = 0.425). Treatment × Cohort interaction was not significant (F = 0.55, p = 0.46).
Conclusions:
Across three decades, the use of chronotherapy was consistently associated with shorter LOS in bipolar depression, despite major changes in clinical practice, organizational structure, and environmental circadian stressors. While causality cannot be inferred due to the observational design, these findings suggest that TSD-based chronotherapeutic interventions may represent a promising approach within acute inpatient care pathways, potentially contributing to improved hospitalization trajectories and discharge readiness in bipolar depression.
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