Bright Light Therapy in the Morning or Midday for the Treatment of Nonseasonal Depression in Bipolar Disorder (LuBi): A Dose-Escalation Phase 1/2 Randomized Double-Blind Trial

Pierre A. Geoffroy, MD, PhD ; Sylvie Chevret, MD, PhD ; Sibylle Mauries, MD ; Cendrine Chaffaut, MSc ; Ali Amad, MD, PhD ; Frank Bellivier, MD, PhD ; Victoire Benard, MD, PhD ; Philippe Courtet, MD, PhD ; Caroline Dubertret, MD, PhD ; Philip Gorwood, MD, PhD ; Nicolas Mazer, MD ; Lila Mekaoui, MD ; Emilie Olié, MD, PhD ; Guillaume Pataud, MD ; Guillaume Vaiva, MD, PhD ; Michel Lejoyeux, MD, PhD ; Dorothy Sit, MD, PhD ; Julia Maruani, MD, MSc

J Clin Psychiatry 2025;86(3):25m15826

Abstract

Objective: This dose-escalation study aimed to evaluate the tolerance (hypomanic symptoms) and efficacy of bright light therapy (BLT) in depressed patients with bipolar disorder (BD) with mood stabilizers, using different schedules (duration and escalation), applied in morning or midday.

Methods: Patients with BD I or II (DSM-IV TR) followed a 1-week placebo phase and were randomized to morning or midday BLT with dose escalation from 7.5 to 45 minutes/d, until September 2023. Inter- and intrasubject escalation were performed, with dose adjustments based on dose-limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD) and target ceiling dose (TCD) of BLT exposure. The primary outcome measure, DLT, was assessed weekly after each dose initiation or increase and defined as a hypomanic switch (Young Mania Rating Scale [YMRS] score ≥12/60) or subsyndromic hypomanic symptoms (YMRS score 8–12).

Results: Both groups reached the starting dose of 45 minutes without reaching the MTD or TCD, enrolling 38 patients (morning = 18 and midday = 16) and demonstrating good tolerance and acceptability. Two patients (6%) experienced a hypomanic switch at 45 minutes: 1 in the morning group (week 1) and 1 in the midday group (week 4). Five patients had subsyndromic hypomania. All symptoms improved within 3 days after dose reduction. Depressive symptoms (Montgomery Asberg Depression Rating Scale, P = .007) and Clinical Global Impression (CGI) scores (P < .001 for severity, P = .01 for improvement) significantly improved over time. A cumulative exposure effect was observed on CGI improvement (P = .038), alongside a starting dose effect over the weeks on CGI severity (P < .001) and the Flexibility Circadian Type Inventory (P = .042). The comparison between groups shows a higher CGI improvement score in the morning group (P = .035).

Conclusions: BLT is a viable antidepressant strategy for BD, safely starting at 45 minutes regardless of timing. Occurring hypomanic symptoms, if any, resolve quickly after dose reduction, provided there is careful monitoring.

Trial Registration: ClinicalTrials.gov identifier: NCT03396744.

J Clin Psychiatry 2025;86(3):25m15826

Author affiliations are listed at the end of this article.

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