Melatonin administration increased sleep time only during the first daytime sleep episode. As illustrated in , PSG recordings demonstrated that subjects had longer TST with melatonin compared with placebo during Day Sleep 1, but that melatonin administration had no effect on TST during Day Sleep 2. Similar results were obtained for subjective sleep times recorded on sleep logs. Sleep parameters from PSG and sleep logs are listed in and , respectively. On Day Sleep 1, subjects had 24 min more sleep after melatonin compared with placebo according to PSG and 26 min more sleep according to sleep logs. There were four significant drug by Day interactions in the Baseline vs. Day Sleep 1 planned contrasts – PSG TST (F1,19 = 6.05, P = 0.024), sleep log TST (F1,19 = 7.09, P = 0.015), PSG sleep efficiency (F1,19 = 5.97, P = 0.024) and PSG WASO (F1,19 = 5.06, P = 0.036). These interactions indicated that the sleep parameters differed between Baseline and Day Sleep 1 during only one session, i.e, during either the melatonin or placebo session. To interpret the interactions, we performed paired-samples t-tests between the placebo and melatonin sessions for each sleep parameter. The t-tests showed that on Day Sleep 1 after melatonin, subjects had longer sleep durations (PSG: t1,20 = 2.658, P = 0.015; Sleep Log: t1,19 = 2.585, P = 0.018), higher sleep efficiencies (t1,20 = 2.67, P = 0.015) and less WASO (t1,20 = −2.595, P = 0.017), compared with after placebo. There were no differences in these sleep parameters between the melatonin and placebo sessions at baseline. Furthermore, there were no drug by day interactions for the sleep parameters examined in the planned contrasts between Baseline and Day Sleep 2; melatonin administration did not affect sleep on Day Sleep 2.
Figure 2 Total sleep times (mean ± SEM) recorded with polysomnography during the melatonin session (●) and placebo session (○). B1 = Baseline 1; B2 = Baseline 2; D1 = Day Sleep 1; D2 = Day Sleep 2; R = Recovery. Melatonin or placebo was (more ...)
Sleep parameters from polysomnography (mean ± SD)
Sleep parameters from subjects’ sleep logs (mean ± SD)
Further analysis of the daytime sleep episodes by PSG showed that melatonin exerted its effect on sleep during Day Sleep 1 mainly by increasing sleep duration during the second half of the sleep episode (see ). Subjects had an average of 24 ± 42 min more sleep during the second half of Day Sleep 1 after melatonin compared with after placebo, and repeated measures ANOVA with factors drug, day and half showed a significant drug by half interaction (F1,18 = 4.99, P = 0.038). shows that subjects slept for nearly the entire 4 h during the first half of all daytime sleep episodes. The decrease in daytime sleep occurred during the second half of the daytime sleep episodes. Again, melatonin significantly attenuated the decrease only during day Sleep 1.
Figure 3 Amount of polysomnographic sleep (mean ± SEM) during the first and second halves of the day sleep episodes (first and last 4 h) during the melatonin session (●) and the placebo session (○). *P < 0.05 between melatonin and (more ...)
Subjects slept less during the recovery night than during baseline (see ), most probably because they had only been awake for 7 h before recovery bedtime. Subjects had average PSG TSTs ranging from 3.9 to 7.9 h (mean TST = 7.0 ± 0.8 h) during the recovery night after placebo and from 5.0 to 7.8 h (mean TST = 6.8 ± 1.0 h) during the recovery night after melatonin. There were no significant effects of melatonin administration on any PSG or sleep log recovery sleep parameters, i.e. no significant drug by day interactions in the Baseline vs. Recovery planned contrasts. Total sleep time on the recovery nights was not correlated with the amount of sleep subjects obtained during the two daytime sleep episodes, nor was it correlated with the level of sleepiness exhibited during the night shift (average sleep latencies measured during the MSLTs, see below).
Salivary melatonin levels
After taking the placebo pill, subjects’ melatonin levels at bedtime were 16.9 ± 26.0 pg mL−1 and 14.7 ± 16.1 pg mL−1 on Day 1 and Day 2, and at wake time were 2.1 ± 2.0 and 1.7 ± 1.7 pg mL−1 on Day 1 and Day 2. Bedtime melatonin levels 0.5 h after taking the melatonin pill were 145.3 ± 103.8 and 142.0 ± 104 pg mL−1 on Days 1 and 2, respectively; at wake time, 8.5 h after taking the melatonin pill, melatonin levels were 24.2 ± 25.9 and 20.5 ± 15.8 pg mL−1 on Days 1 and 2. Repeated measures ANOVA with factor drug (melatonin, placebo), day (Day Sleep 1, Day Sleep 2) and time (bedtime, wake time) showed a significant main effect of drug. Thus, administration of the melatonin tablets produced significantly higher levels of salivary melatonin both at bedtime and wake time compared with placebo (F1,19 = 44.73, P < 0.001). There was no effect of day; melatonin levels were similar after melatonin administration on Day 1 and Day 2. The levels of melatonin produced by the melatonin pill were not significantly correlated with sleep duration during either of the daytime sleep episodes.
Subjective reports of sleepiness
illustrates the subjects’ SSS ratings at bedtime, wake time, and during the night shifts. On Day Sleep 1, subjects were sleepier at bedtime after taking melatonin vs. after taking placebo. The planned contrasts between Baseline and Day Sleep 1 showed a significant Drug by Day interaction for the SSS ratings made at bedtime (F1,20 = 8.155, P = 0.01), and the paired-samples t-test showed that SSS ratings were significantly higher at bedtime after taking melatonin compared with placebo (t1,20 = 3.423, P = 0.003). Melatonin administration did not significantly affect SSS ratings at bedtime on Day Sleep 2, or at wake time on either Day Sleep 1 or Day Sleep 2. Melatonin had no effect on the VAS sleepiness ratings.
Figure 4 Average Stanford sleepiness scale ratings (mean ± SEM) from bedtime questionnaires, wake time questionnaires, and test bouts during the night shifts. 1 = ‘feeling active and vital; alert; wide awake’ and 7 = ‘almost in (more ...)
Sleepiness increased as the night shifts progressed (), but there were no significant differences between melatonin and placebo on night shift 2, the night shift after the subjects had taken melatonin or placebo before daytime sleep.
Sleepiness during the night shifts
shows the MSLT data from the night shifts. Sleep latencies decreased as the night progressed and were shorter during night shift 1 compared with night shift 2. The same pattern was observed in SSS ratings, i.e. increasing sleepiness as the night progressed and more sleepiness during night shift 1 (). Melatonin administration before Day Sleep 1 had no effect on the MSLT during the subsequent (second) night shift. A repeated measures ANOVA with factors Drug, Night Shift, and Nap showed a significant effect of Night Shift (F1,20 = 48.76, P < 0.001) and Nap number (F1,20 = 22.43, P < 0.001), but no effect of drug.
Figure 5 Average sleep latencies (mean ± SEM) from the four MSLT naps administered during the night shifts. M = Melatonin session; P = Placebo session. Filled symbols indicate the melatonin session and open symbols indicate the placebo session. Triangles (more ...)
Performance and mood during the night shift
shows two examples of night shift mood and performance measures: general activation on the ADACL and PVT lapses. In general, subjects had better mood and performance during night shift 2 compared with night shift 1, and performance worsened and mood declined across the night shift. Repeated measures ANOVA showed significant main effects of Day and Test Bout for nearly all measures. On the other hand, of more than 20 mood and performance variables measured by the neurobehavioral testing battery during the night shifts, only one showed a main effect of melatonin administration – the subjective rating of effort to achieve performance on the test battery. Further inspection showed that this was an effect of session rather than melatonin administration; subjects reported expending more effort during night shift 1 of the melatonin session (before melatonin was administered for daytime sleep) than during the other night shifts.
Figure 6 Examples of performance test results from the neurobehavioural assessment battery during the night shifts. Filled symbols indicate the melatonin session and open symbols indicate the placebo session. Triangles indicate the first night shift and boxes (more ...)
About half of the subjects had high sleep efficiencies during all 4 daytime sleep episodes, i.e. even during daytime sleep after placebo administration. In these subjects, there was no room for melatonin to confer any substantial benefit over placebo. It was of interest therefore to explore the impact of melatonin administration on those who had difficulty in sleeping during the day. To do these post hoc analyses, we divided our subjects into two groups – those who had a sleep efficiency <85% during either daytime sleep episode of the placebo session (poorer sleepers, n = 11) and those whose sleep efficiencies were >85% during both daytime sleep episodes of the placebo session (better sleepers, n = 9).
In poorer sleepers, melatonin administration resulted in 45 ± 47 more minutes of sleep during Day Sleep 1 compared with placebo, and 13 ± 82 min more sleep during Day Sleep 2 (TST from PSG). Thus, melatonin administration did have a greater impact on poorer sleepers. However, the increase in sleep duration still occurred primarily during the first daytime sleep episode.
It was of interest to see if we could distinguish other differences between better and poorer sleepers aside from their ability to sleep during the day. Poorer sleepers were on average 3.5 years older than better sleepers (28.3 ± 5.1 vs. 24.8 ± 4.1 years), but this difference was not statistically significant (independent samples t-test: t1,18 = −1.654, P = 0.12). The poorer sleepers had baseline sleep times well within normal limits, but interestingly, their baseline sleep durations were significantly lower than those of better sleepers. Poorer sleepers obtained an average of 7.4 ± 0.4 h of sleep during the four baseline sleep episodes compared with better sleepers whose average TST during baseline was 7.7 ± 0.1 h (independent samples t-test: t1,18 = 3.903, P = 0.001). There were no differences in sex distribution or morningness– eveningness between the poorer sleepers and the better sleepers.