Research from JAMA Psychiatry — Bright Light Treatment of Winter Depression — A Placebo-Controlled Trial

Context: Phase response curves (PRCs) to melatonin exist, but none compare different doses of melatonin using the same protocol. Objective: The aim was to generate a PRC to 0.5 mg of oral melatonin and compare it to our previously published 3.0 mg PRC generated using the same protocol. Design and Setting: The study included two 5-d sessions in the laboratory, each preceded by 7–9 d of fixed sleep times. Each session started and ended with a phase assessment to measure the dim light melatonin onset (DLMO). In between were 3 d in an ultradian dim light (<150 lux)/dark cycle (light:dark, 2.5:1.5). Participants: Healthy adults (16 men, 18 women) between the ages of 18 and 42 yr participated in the study. Interventions: During the ultradian days of the laboratory sessions, each participant took one pill per day at the same clock time (0.5 mg melatonin or placebo, double blind, counterbalanced). Main Outcome Measure: Phase shifts to melatonin were derived by subtracting the phase shift to placebo. A PRC with time of pill administration relative to baseline DLMO and a PRC relative to midpoint of home sleep were generated. Results: Maximum advances occurred when 0.5 mg melatonin was taken in the afternoon, 2–4 h before the DLMO, or 9–11 h before sleep midpoint. The time for maximum phase delays was not as distinct, but a fitted curve peaked soon after wake time. Conclusions: The optimal administration time for advances and delays is later for the lower dose of melatonin. When each dose of melatonin is given at its optimal time, both yield similarly sized advances and delays.

Various combinations of interventions were used to phase-delay circadian rhythms to correct their misalignment with night work and day sleep. Young participants (median age = 22, n= 67) participated in 5 consecutive simulated night shifts (2300 to 0700) and then slept at home (0830 to 1530) in darkened bedrooms. Participants wore sunglasses with normal or dark lenses (transmission 15% or 2%) when outside during the day. Participants took placebo or melatonin (1.8 mg sustained release) before daytime sleep. During the night shifts, participants were exposed to a moving (delaying) pattern of intermittent bright light (~5000 lux, 20 min on, 40 min off, 4-5 light pulses/night) or remained in dimlight (~150 lux). There were 6 intervention groups ranging fromthe least complex (normal sunglasses) to the most complex (dark sunglasses + bright light + melatonin). The dim light melatonin onset (DLMO) was assessed before and after the night shifts (baseline and final), and 7 h was added to estimate the temperature minimum (Tmin). Participants were categorized by their amount of reentrainment based on their final Tmin: not re-entrained (Tmin before the daytime dark/sleep period), partially re-entrained (Tmin during the first half of dark/sleep), or completely re-entrained (Tmin during the second half of dark/ sleep). The sample was split into earlier participants (baseline Tmin = 0700, sunlight during the commute home fell after the Tmin) and later participants (baseline Tmin > 0700). The later participants were completely re-entrained regardless of intervention group, whereas the degree of re-entrainment for the earlier participants depended on the interventions. With bright light during the night shift, almost all of the earlier participants achieved complete re-entrainment, and the phase delay shift was so large that darker sunglasses and melatonin could not increase its magnitude. With only room light during the night shift, darker sunglasses helped earlier participants phase-delay more than normal sunglasses, but melatonin did not increase the phase delay. The authors recommendthecombination of intermittent bright light during the night shift, sunglasses (as dark as possible) during the commute home, and a regular, early daytime dark/sleep period if the goal is complete circadian adaptation to night-shift work.