Comparison of Royal Canadian Navy Watchstanding Schedules.

INTRODUCTION: Life on board a naval vessel is exceptionally demanding. Workdays for naval sailors can quite easily become 18+ hours long when watch schedules, training, and drills/evolutions are taken into account. Rotating watches and short off-watch periods can force sailors into a biphasic sleep pattern that is not sufficiently restful or a rotating pattern that is impossible to adapt to. MATERIALS AND METHODS: Six different watch systems were evaluated over four separate at-sea trials. Engineering and tactical/combat departments have had different watch systems in the past because of constraints related to the specific environment in which they work. Therefore, two of the watch systems were engineering-specific watch evaluations, three of the systems were specific to tactical/combat departments, and one watch system was evaluated with the entire company of the naval vessel. RESULTS: Both two-section (1-in-2) watch systems and three-section (1-in-3) watch systems were evaluated, which involve two or three shifts of sailors rotating through a full continuous 24-h day, respectively. Moving beyond three rotations of sailors is impossible on Canadian naval vessels due to bunk space and other limitations. The best watch system that we evaluated with respect to fatigue and quality of life at sea was the 1-in-3 straight 8-h shift system that was tested for the entire ships' company. The system has a single 8-h daily watch obligation (red watch, 4:00 am-12:00 pm; white watch 12:00 pm-8:00 pm; and blue watch, 8:00 pm-4:00 am). The best 1-in-2 system was the 8-4-4-8 system in which sailors are on-watch for 8 h, off-watch for 4 h, on-watch for 4 h, and then rest for 8 h. Both of these two systems have the advantage of equitably sharing the Window of Circadian Low (from about midnight to about 8:00 am), especially when melatonin concentration in the body is usually at its peak, between 2:00 am and 6:00 am. CONCLUSIONS: The goal of this work was to comprehensively evaluate both submarine and surface fleet watch systems. We were able to develop alternative watch systems that increased Royal Canadian Navy operational readiness and improved the quality of life of our sailors at sea.

The Importance of Validating Sleep Behavior Models for Fatigue Management Software in Military Aviation.

INTRODUCTION: The propensity for air mobility missions to exhaust aircrews is strongly dependent on operational tempo. Most flying is performed during periods of low to moderate operational tempo, but a major flight safety risk can emerge when operational tempo becomes very high. This risk can be managed by software tools that contain fatigue and sleep behavior modeling, but optimization/validation of the model using the specific target population is required to ensure that the modeled predictions are accurate. The goal of the study was to validate the sleep behavior model settings for a fatigue modeling tool that is used within the RCAF, the Fatigue Avoidance Scheduling Tool, taking into account the organizational requirements for pre- and postflight routines, especially within the Air Mobility force. MATERIALS AND METHODS: Four Royal Canadian Air Force Air Mobility Squadrons from Canadian Forces Base Trenton took part in this trial over a 3-month period (May 3 to August 21, 2016). All 22 missions of the trial included long-range transmeridian flights. All members of the participating aircrew wore wrist actigraphs to measure their sleep. We compared cognitive effectiveness modeling scenarios (preharmonization) based on the SAFTE-FAST sleep behavior model with its default settings against cognitive effectiveness modeling scenarios based on actigraphically-measured sleep. The measured sleep was then harmonized against the predicted sleep to optimize accuracy of the sleep behavior algorithm. During the harmonization process, the "Autosleep" prediction settings were optimized to match the actigraphically-measured sleep timings. RESULTS: Prior to the harmonization effort, the sleep behavior algorithm overpredicted the sleep obtained by CAF Aircrews. The most significant adjustment to the sleep behavior model was the increase in commute time to account for briefing, flight planning, debriefing, and postflight activities. Following harmonization, the sleep behavior model provided nearly perfect estimates of overall fatigue risk against missions modeled with actigraphically-measured sleep. For both measured and predicted sleep, most of the time in flight was in a low-fatigue, high-cognitive effectiveness state (90%-95% cognitive effectiveness). CONCLUSIONS: Current Fatigue Risk Management Systems require accurate fatigue and sleep behavior modeling, which can only be achieved by studying specific target populations to determine their culture of work/rest routines, and optimizing sleep behavior model settings accordingly.

Blunted Nocturnal Salivary Melatonin Secretion Profiles in Military-Related Posttraumatic Stress Disorder.

Background: Sleep disturbances are a hallmark of posttraumatic stress disorder (PTSD), yet few studies have evaluated the role of dysregulated endogenous melatonin secretion in this condition. Methods: This study compared the sleep quality and nocturnal salivary melatonin profiles of Canadian Armed Forces (CAF) personnel diagnosed with PTSD, using the Clinician Administered PTSD Scale (CAPS score ≥50), with two healthy CAF control groups; comprising, a "light control" (LC) group with standardized evening light exposure and "normal control" (NC) group without light restriction. Participants were monitored for 1-week using wrist actigraphy to assess sleep quality, and 24-h salivary melatonin levels were measured (every 2h) by immunoassay on the penultimate day in a dim-light (< 5 lux) laboratory environment. Results: A repeated measures design showed that mean nocturnal melatonin concentrations for LC were higher than both NC (p = .03) and PTSD (p = .003) with no difference between PTSD and NC. Relative to PTSD, NC had significantly higher melatonin levels over a 4-h period (01 to 05 h), whereas the LC group had higher melatonin levels over an 8-h period (23 to 07 h). Actigraphic sleep quality parameters were not different between healthy controls and PTSD patients, likely due to the use of prescription sleep medications in the PTSD group. Conclusions: These results indicate that PTSD is associated with blunted nocturnal melatonin secretion, which is consistent with previous findings showing lower melatonin after exposure to trauma and suggestive of severe chronodisruption. Future studies targeting the melatonergic system for therapeutic intervention may be beneficial for treatment-resistant PTSD.

Sleep deficits in the High Arctic summer in relation to light exposure and behaviour: use of melatonin as a countermeasure.

BACKGROUND: There are conflicting reports regarding seasonal sleep difficulties in polar regions. Herein we report differences in actigraphic sleep measures between two summer trials (collected at Canadian Forces Station Alert, 82.5°N, in 2012 and 2014) and evaluate exogenous melatonin for preventing/treating circadian phase delay due to nocturnal light exposure. METHODS: Subjects wore actigraphs continuously to obtain sleep data. Following seven days of actigraphic recording the subjects filled out questionnaires regarding sleep difficulty and psychosocial parameters and subsequently remained in dim light conditions for 24 hours, during which saliva was collected bihourly to measure melatonin. During Trial 2, individuals who reported difficulty sleeping were prescribed melatonin, and a second saliva collection was conducted to evaluate the effect of melatonin on the circadian system. RESULTS: Trial 1 subjects collectively had late dim light melatonin onsets and difficulty sleeping; however, the Trial 2 subjects had normally timed melatonin rhythms, and obtained a good quantity of high-quality sleep. Nocturnal light exposure was significantly different between the trials, with Trial 1 subjects exposed to significantly more light between 2200 and 0200h. Melatonin treatment during Trial 2 led to an improvement in the subjective sleep difficulty between the pre- and post-treatment surveys; however there were no significant differences in the objective measures of sleep. CONCLUSIONS: The difference in sleep and melatonin rhythms between research participants in June 2012 and June 2014 is attributed to the higher levels of nocturnal light exposure in 2012. The avoidance of nocturnal light is likely to improve sleep during the Arctic summer.

Light treatment improves sleep quality and negative affectiveness in high arctic residents during winter.

The seasonal extremes of photoperiod in the high Arctic place particular strain on the human circadian system, which leads to trouble sleeping and increased feelings of negative affect in the winter months. To qualify for our study, potential participants had to have been at Canadian Forces Station (CFS) Alert (82° 30' 00″ N) for at least 2 weeks. Subjects filled out questionnaires regarding sleep difficulty, psychological well-being and mood and wore Actigraphs to obtain objective sleep data. Saliva was collected at regular intervals on two occasions, 2 weeks apart, to measure melatonin and assess melatonin onset. Individuals with a melatonin rhythm that was in disaccord with their sleep schedule were given individualized daily light treatment interventions based on their pretreatment salivary melatonin profile. The light treatment prescribed to seven of the twelve subjects was effective in improving sleep quality both subjectively, based on questionnaire results, and objectively, based on the actigraphic data. The treatment also caused a significant reduction in negative affect among the participants. Since the treatment is noninvasive and has minimal associated side effects, our results support the use of the light visors at CFS Alert and other northern outposts during the winter for individuals who are experiencing sleep difficulty or low mood.

Sleep and the endogenous melatonin rhythm of high arctic residents during the summer and winter.

The seasonal extremes of photoperiod in high latitudes place particular strain on the human circadian system. Arctic residence has been associated with poor sleep in both summer and winter. The goal of the work reported here was to study the circadian rhythms of individuals living in the high Arctic by measuring sleep variables and the timing of melatonin production. Two research trials were conducted in the built environment of CFS Alert (82° 29' 58″ N). Participants wore motion logging devices (actigraphs), which measure ambient light as well as motion, for 1week to provide data on sleep quantity, quality and light exposure. On the penultimate day of each trial, the participants were maintained together in a gymnasium with lounge chairs and saliva was collected at regular intervals to measure melatonin and assess the dim light melatonin onset (DLMO), offset (MelOFF), 50% rise and fall times of the whole profile and total production. In general, sleep duration was found to be significantly different between the January and June data collections at CFS Alert, with participants in June sleeping 50min on average less each day compared to their January counterparts. In June sleep was mistimed in many subjects relative to circadian phase as evidenced by the melatonin rhythm. Exposure to bright evening light was the most likely causal factor and should be avoided in the Arctic summer. The Arctic summer represents a particularly challenging environment for obtaining sufficient sleep. This has implications for the cognitive performance of staff during work hours.

Phase advance with separate and combined melatonin and light treatment.

INTRODUCTION: Melatonin and light treatment are recommended for hastening adaptation to time zone change. We evaluated an afternoon regimen of 3 mg sustained release (SR) melatonin with and without next morning green light treatment for circadian phase advance. Effects of melatonin and light were tested separately and then combined to determine if the total phase change is additive or synergistic. MATERIAL AND METHODS: For each condition (melatonin, placebo, light, melatonin plus light), 11 subjects spent from Tuesday evening until Friday afternoon in the laboratory. For all four conditions, the following sleep schedule was maintained: night 1, 2345 to 0630 hours, night 2, 1600 to 0530 hours, and night 3, 2345 to 0700 hours. For the light-only condition, light treatment was administered between 0700 and 0800 hours on Thursday. For melatonin-only or placebo conditions, capsules were administered at 1600 hours on Wednesday. For the combined condition, melatonin was administered at 1600 hours on Wednesday with light treatment between 0600 and 0700 hours on Thursday. Circadian phase was assessed by calculating dim light melatonin onset (DLMO) from salivary melatonin, using a mean baseline +2 standard deviations (BL+2 SD) threshold. For all four conditions, pre-treatment and post-treatment DLMO assessments were on Tuesday and Thursday evenings, respectively. RESULTS: Phase advances were: melatonin at 1600 hours, 0.72 h p<0.005, light treatment from 0700 to 0800 hours, 0.31 h, non-significant, and the combined treatment, 1.04 h p<0.0002. CONCLUSION: The phase advance from the combination of afternoon melatonin with next morning light is additive.

Melatonin treatment for eastward and westward travel preparation.

INTRODUCTION: Melatonin is recommended for hastening adaptation to phase shift, but there is little information on appropriate formulations. MATERIALS AND METHODS: We evaluated the efficacy of three melatonin formulations for circadian phase advance and delay: (a) 3 mg regular release (RR), (b) 3 mg sustained release (SR), and (c) 3 mg surge-sustained release (SSR; consisting of 1 mg RR and 2 mg SR). Circadian phase was assessed by salivary melatonin dim light melatonin onset (DLMO) or offset (MelOff) using thresholds of (1) 1.0 pg/ml and (2) mean baseline + 2 standard deviations (BL + 2SD). Subjects spent from Tuesday evenings until Thursday in the laboratory. Melatonin (or placebo) was administered at 1600 hours (phase advance) Wednesday, with DLMO assessment on Tuesday and Thursday and at 0600 hours (phase delay) Wednesday, with DLMO assessment Tuesday, Wednesday, and MelOff Thursday morning. Phase advances using the 1.0 pg/ml DLMO were as follows: placebo, 0.73 h; RR, 1.23 h (p < 0.003); SR, 1.44 h (p < 0.0002); SSR, 1.16 h (p < 0.012), with no difference between formulations. RESULTS AND DISCUSSION: Similar but smaller phase advances were found with BL + 2SD. Using MelOff, posttreatment phase position for the RR formulation was delayed compared to placebo by 1.12 h (p < 0.012), 1.0 pg/ml, and 0.75 h (p < 0.036), BL+2SD. Phase shifts for the SR and SSR conditions could not be determined due to persistent high melatonin levels during sampling times. Similar phase advances were induced by all formulations, and slow clearance of slow release preparations impeded the determination of phase delays. CONCLUSION: Appropriately timed 0.5 mg melatonin doses may avoid these problems.

Timing light treatment for eastward and westward travel preparation.

Jet lag degrades performance and operational readiness of recently deployed military personnel and other travelers. The objective of the studies reported here was to determine, using a narrow bandwidth light tower (500 nm), the optimum timing of light treatment to hasten adaptive circadian phase advance and delay. Three counterbalanced treatment order, repeated measures studies were conducted to compare melatonin suppression and phase shift across multiple light treatment timings. In Experiment 1, 14 normal healthy volunteers (8 men/6 women) aged 34.9+/-8.2 yrs (mean+/-SD) underwent light treatment at the following times: A) 06:00 to 07:00 h, B) 05:30 to 07:30 h, and C) 09:00 to 10:00 h (active control). In Experiment 2, 13 normal healthy subjects (7 men/6 women) aged 35.6+/-6.9 yrs, underwent light treatment at each of the following times: A) 06:00 to 07:00 h, B) 07:00 to 08:00 h, C) 08:00 to 09:00 h, and a no-light control session (D) from 07:00 to 08:00 h. In Experiment 3, 10 normal healthy subjects (6 men/4 women) aged 37.0+/-7.7 yrs underwent light treatment at the following times: A) 02:00 to 03:00 h, B) 02:30 to 03:30 h, and C) 03:00 to 04:00 h, with a no-light control (D) from 02:30 to 03:30 h. Dim light melatonin onset (DLMO) was established by two methods: when salivary melatonin levels exceeded a 1.0 pg/ml threshold, and when salivary melatonin levels exceeded three times the 0.9 pg/ml sensitivity of the radioimmunoasssy. Using the 1.0 pg/ml DLMO, significant phase advances were found in Experiment 1 for conditions A (p < .028) and B (p < 0.004). Experiment 2 showed significant phase advances in conditions A (p < 0.018) and B (p < 0.003) but not C (p < 0.23), relative to condition D. In Experiment 3, only condition B (p < 0.035) provided a significant phase delay relative to condition D. Similar but generally smaller phase shifts were found with the 2.7 pg/ml DLMO method. This threshold was used to analyze phase shifts against circadian time of the start of light treatment for all three experiments. The best fit curve applied to these data (R(2) = 0.94) provided a partial phase-response curve with maximum advance at approximately 9-11 h and maximum delay at approximately 5-6 h following DLMO. These data suggest largest phase advances will result when light treatment is started between 06:00 and 08:00 h, and greatest phase delays will result from light treatment started between 02:00 to 03:00 h in entrained subjects with a regular sleep wake cycle (23:00 to 07:00 h).

Fatigue countermeasures in aviation.

Pilot fatigue is a significant problem in modern aviation operations, largely because of the unpredictable work hours, long duty periods, circadian disruptions, and insufficient sleep that are commonplace in both civilian and military flight operations. The full impact of fatigue is often underappreciated, but many of its deleterious effects have long been known. Compared to people who are well-rested, people who are sleep deprived think and move more slowly, make more mistakes, and have memory difficulties. These negative effects may and do lead to aviation errors and accidents. In the 1930s, flight time limitations, suggested layover durations, and aircrew sleep recommendations were developed in an attempt to mitigate aircrew fatigue. Unfortunately, there have been few changes to aircrew scheduling provisions and flight time limitations since the time they were first introduced, despite evidence that updates are needed. Although the scientific understanding of fatigue, sleep, shift work, and circadian physiology has advanced significantly over the past several decades, current regulations and industry practices have in large part failed to adequately incorporate the new knowledge. Thus, the problem of pilot fatigue has steadily increased along with fatigue-related concerns over air safety. Accident statistics, reports from pilots themselves, and operational flight studies all show that fatigue is a growing concern within aviation operations. This position paper reviews the relevant scientific literature, summarizes applicable U.S. civilian and military flight regulations, evaluates various in-flight and pre-/postflight fatigue countermeasures, and describes emerging technologies for detecting and countering fatigue. Following the discussion of each major issue, position statements address ways to deal with fatigue in specific contexts with the goal of using current scientific knowledge to update policy and provide tools and techniques for improving air safety.

Circadian phase delay induced by phototherapeutic devices.

INTRODUCTION: The Canadian Forces has initiated a multiple study project to optimize circadian phase changes using appropriately timed phototherapy and/or ingestion of melatonin for those personnel on long-range deployments and shift workers. The work reported here compared four phototherapeutic devices for efficacy in effecting circadian phase delays. METHODS: In a partially counterbalanced treatment order, 14 subjects (7 men and 7 women), ages 18-51 yr, participated in 5 weekly experimental sessions of phototherapy with 4 different phototherapy devices (light tower, light visor, Litebook, LED spectacles) and a no-phototherapy control. Phototherapy was applied from 24:00 to 02:00 on night. (1) Dim light melatonin onset (DLMO) was assessed on night 1 and night. (2) Subjects were tested for psychomotor performance (serial reaction time, logical reasoning, and serial subtraction tasks) and completed the Stanford Sleepiness Scale on night 1 at 19:00, 23:00, 01:00, 02:00, and 03:00. After phototherapy, subjects completed a phototherapy side-effects questionnaire. RESULTS: All phototherapy devices produced melatonin suppression and significant phase delays. Sleepiness was significantly decreased with the light tower, the light visor, and the Litebook. Task performance was only slightly improved with phototherapy. The LED spectacles and light visor caused greater subjective performance impairment, more difficulty viewing the computer monitor and reading printed text than the light tower or the Litebook. The light visor, the Litebook, and the LED spectacles caused more eye discomfort than the light tower. CONCLUSIONS: The light tower was the best device, producing melatonin suppression and circadian phase change while relatively free of side effects.

SSRI effects on pyschomotor performance: assessment of citalopram and escitalopram on normal subjects.

INTRODUCTION: Standard aeromedical doctrine dictates that aircrew receiving treatment for depression are grounded during treatment and follow-up observation, generally amounting to at least 1 yr. The Canadian Forces has initiated a program to return selected aircrew being treated for depression to restricted flying duties once stabilized on an approved antidepressant with resolution of depression. The currently approved medications are sertraline (a selective serotonin reuptake inhibitor) and bupropion (noradrenaline and dopamine reuptake inhibitor). This study was undertaken to determine whether or not citalopram or escitalopram affect psychomotor performance. METHOD: In a double-blind crossover protocol with counter-balanced treatment order, 24 normal volunteer subjects (14 men and 10 women) were assessed for psychomotor performance during placebo, citalopram (40 mg), and escitalopram (20 mg) treatment. Each treatment arm lasted 2 wk, involving a daily morning ingestion of one capsule. There was a 1-wk washout period between medication courses. Subjects completed a drug side-effect questionnaire and were tested on three psychomotor test batteries once per week. RESULTS: Neither citalopram nor escitalopram affected serial reaction time, logical reasoning, serial subtraction, multitask, or MacWorth clock task performance. CONCLUSIONS: While we found some of the expected side effects due to citalopram and escitalopram, there was no impact on psychomotor performance. These findings support the possibility of using citalopram and escitalopram for returning aircrew to restricted flight duties (non-tactical flying) under close observation as a maintenance treatment after full resolution of depression.

Motion-sickness medications for aircrew: impact on psychomotor performance.

INTRODUCTION: Motion sickness remains a significant problem for aircrew both in the flying environment (airsickness) and for aircrew deployed at sea (seasickness). While some anti-motion-sickness medications provide reasonable efficacy, adverse neurocognitive effects limit their use in military personnel engaged in safety-sensitive operational roles such as flying. The purpose of this study was to assess the impact on psychomotor performance of promethazine, meclizine, and dimenhydrinate and to determine if the addition of pseudoephedrine or damphetamine to promethazine would ameliorate its adverse effects. METHODS: There were 21 subjects (11 men, 10 women), aged 22-59, who were assessed for psychomotor performance on 4 tasks as well as with sleepiness and drug side-effects questionnaires. Psychomotor testing was conducted prior to, and for 7 h after, ingestion of a single dose of each of placebo, promethazine 25 mg, meclizine 50 mg, dimenhydrinate 50 mg, promethazine 25 mg plus pseudoephedrine 60 mg, and promethazine 25 mg plus d-amphetamine 10 mg. RESULTS: Relative to placebo, promethazine, meclizine, and promethazine plus pseudoephedrine impaired performance on all four tasks [serial reaction time (SRT), logical reasoning (LRT), serial subraction (SST), and multitask (MT)]. Dimenhydrinate impaired performance on the SRT only. Promethazine plus d-amphetamine did not impair performance on any task nor did it result in increased sleepiness. The times to recovery of normal performance for SRT with promethazine, meclizine, dimenhydrinate, and promethazine plus pseudoephedrine were > 7.25, 7.25, 4.25, and 7.25 h, respectively; for LRT were > 7.25, > 7.25, ns, and 7.25 h; for SST were > 7.25, > 7.25, ns, and 7.25 h; for MT were 7.25, 7.25, ns, and 7.25 h. Recovery times to baseline sleepiness levels for promethazine, meclizine, dimenhydrinate, and promethazine plus pseudoephedrine were 7.25, > 7.25, 6.25, and > 7.25 h. CONCLUSION: Only promethazine plus d-amphetamine was free from impact on psychomotor performance and did not increase sleepiness.

Sleep-inducing pharmaceuticals: a comparison of melatonin, zaleplon, zopiclone, and temazepam.

INTRODUCTION: Current military operations often require pharmaceutical methods to sustain alertness and facilitate sleep in order to maintain operational readiness. This study was designed to compare the sleep-inducing power of four medications. METHOD: There were 9 men and 14 women, ages 21-53 yr, who were assessed for psychomotor performance before and for 7 h after ingestion of a single dose of placebo, zaleplon 10 mg, zopiclone 7.5 mg, temazepam 15 mg, or time-released melatonin 6 mg. The experimental design was a double-blind crossover with counterbalanced treatment order. Subjects wore polysomnographic electrodes to record total sleep and sleep latency during 4-min periods with eyes closed immediately before and after each psychomotor test sequence. Subjective drowsiness was assessed by questionnaire. RESULTS: There were drug x trials interactions for zaleplon, zopiclone, and temazepam for total sleep, sleep latency, and subjective drowsiness. More sleep, shorter sleep latency, and more drowsiness occurred immediately after psychomotor testing compared to before testing for all medications. Melatonin did not cause any sleep prior to psychomotor testing sessions, but caused sleep and reduced sleep latency after psychomotor test sessions from 1 3/4 h to 4 3/4 h post-ingestion. CONCLUSIONS: The sleep-inducing power of the medications before psychomotor testing was zopiclone > zaleplon > melatonin > temazepam. The corresponding effect after psychomotor testing was zopiclone > melatonin > zaleplon > temazepam.

Melatonin and zopiclone as facilitators of early circadian sleep in operational air transport crews.

INTRODUCTION: This study was an extension into an operational setting of previous laboratory work investigating the use of zopiclone and melatonin to facilitate early circadian sleep in transport aircrew. The previous laboratory-based study demonstrated that both melatonin and zopiclone were effective in inducing early circadian sleep without impacting on psychomotor performance after a 7-h sleep period. METHODS: In a repeated measures, placebo-controlled protocol, 30 aircrew flew 3 transatlantic missions over which they took each of the 3 medications (placebo, sustained-release melatonin 2 mg, or zopiclone 5 mg) at an early body clock time (17:00) during their first stopover. They wore wrist actigraphs prior to and throughout the missions, took a single dose of their scheduled medication immediately prior to their early circadian bedtime, and completed a sleep questionnaire on arising from their medicated sleep. RESULTS: The results of the actigraphic data show that relative to placebo, aircrew on melatonin and zopiclone fell asleep more quickly (melatonin: p < 0.01, zopiclone: p < 0.003), slept more (melatonin: p < 0.02, zopiclone: p < 0.005), had fewer awakenings after sleep onset (melatonin: p < 0.004, zopiclone: p < 0.01), and spent less time awake after sleep onset (melatonin: p < 0.01, zopiclone: p < 0.05). The results of the questionnaire data show that relative to placebo, aircrew on melatonin and zopiclone experienced less difficulty getting to sleep (melatonin: p < 0.0001, zopiclone: p < 0.001), had fewer awakenings (melatonin: p < 0.005, zopiclone: p < 0.001), less difficulty returning to sleep after awakening (melatonin: p < 0.0001, zopiclone: p < 0.0001), and reported a better sleep quality (melatonin: p < 0.0003, zopiclone: p < 0.0004). There were no statistically significant differences between melatonin and zopiclone in any of the actigraphic or questionnaire sleep parameters. CONCLUSIONS: Melatonin and zopiclone, in the dosages we used, are equipotent facilitators of early circadian sleep during transmeridian air transport operations.

Impact of melatonin, zaleplon, zopiclone, and temazepam on psychomotor performance.

INTRODUCTION: Modern military operations may require pharmaceutical methods to sustain alertness and facilitate sleep in order to maintain operational readiness. In operations with very limited sleep windows, hypnotics with very short half-lives (e.g., zaleplon, t(1/2) 1 h) are of interest, while with longer sleep opportunities, longer acting agents (e.g., zopiclone, temazepam (t(1/2) 4-6 hours) may be used. This study was designed to compare the effect of a single dose of zaleplon, zopiclone, temazepam, and melatonin on psychomotor performance and to quantify the post-ingestion time required for return to normal performance. METHOD: There were 23 subjects (9 men, 14 women), 21-53 yr of age, assessed for psychomotor performance on 2 test batteries (4 tasks) that included a sleepiness questionnaire. Psychomotor testing was conducted prior to, and for 7 h after, ingestion of a single dose of each of placebo, zaleplon 10 mg, zopiclone 7.5 mg, temazepam 15 mg, and time-released melatonin 6 mg. The experimental design was a double-blind cross-over with counter-balanced treatment order. RESULTS: Zaleplon, zopiclone, and temazepam impaired performance on all four tasks: serial reaction time (SRT), logical reasoning (LRT), serial subtraction (SST), and multitask (MT). Melatonin did not impair performance on any task. The time to recovery of normal performance for SRT during the zaleplon, zopiclone and temazepam conditions were 3.25, 6.25, and 5.25 h respectively; for LRT were 3.25, >6.25, and 4.25 h; for SST were 2.25, >6.25, and 4.25 h, and for MT were 2.25, 4.25, and 3.25 h. The recovery time to baseline subjective sleepiness levels for zaleplon, zopiclone, temazepam, and melatonin were 4.25, >6.25, 5.25, and >4.25 h, respectively. CONCLUSIONS: In spite of a prolonged period of perceived sleepiness, melatonin was superior to zaleplon in causing no impact on performance. The remaining drugs listed in increasing order of performance impact duration are zaleplon, temazepam, and zopiclone.

The impact of Malarone and primaquine on psychomotor performance.

INTRODUCTION: Recent evidence has established the effectiveness of Malarone and primaquine for chemoprophylaxis against Plasmodium falciparum malaria. Both have the advantage of providing causal prophylaxis and therefore require continued dosing for only 1 wk after departure from a malaria endemic area. Canadian Forces aircrews are often placed in situations that put them at risk for malaria infection but the safety of these drugs for use in aircrew has not been ascertained. This study was undertaken to determine whether or not Malarone or primaquine impact psychomotor performance. METHOD: Twenty-eight subjects (20 men and 8 women) ranging from 21 to 52 yr of age were assessed for psychomotor performance on 2 psychomotor test batteries at the end of a 7-d dosing protocol for each of placebo, Malarone, and primaquine treatment, in a double-blind crossover design with counterbalanced treatment order. All subjects were also assessed for psychomotor performance once per week during the 3-wk washout intervals. The daily Malarone dose was atovaquone 250 mg/proguanil 100 mg and the daily primaquine dose was 30 mg of base. In order to verify subject compliance with the medication dosing protocol, blood samples were drawn from all subjects at the end of each of the three 7-d loading protocols. All three medications were packaged in identical gelatin capsules for blinding purposes. At each psychomotor test session, all subjects completed a drug side-effect questionnaire, a mood questionnaire, and a sleepiness/fatigue questionnaire. RESULTS: There was no significant impact of Malarone or primaquine on serial reaction time, logical reasoning, serial subtraction, or multitask performance. With respect to drug adverse effects there were no significant main effects or interactions for the documented adverse effects of these medications (abdominal cramps, epigastric distress, nausea, vomiting, anorexia, headache, coughing and dizziness). CONCLUSIONS: There was no impact of either Malarone or primaquine on psychomotor performance, mood, sleepiness, or fatigue. The usual adverse effects of these medications were not significantly manifested in our subjects. These findings support the possible use of either Malarone or primaquine in aircrew for malaria chemoprophylaxis.

The impact of bupropion on psychomotor performance.

INTRODUCTION: The NDRI (noradrenalin-dopamine re-uptake inhibitor) bupropion SR (sustained-release) is marketed as Wellbutrin* for treatment of depression or Zyban as a smoking cessation aid. There has been considerable interest in the possibility of returning aircrew to restricted flying duties once stabilized on bupropion SR after resolution of depressive symptoms, or while taking bupropion SR for smoking cessation. This study was undertaken to determine whether bupropion SR affects psychomotor performance. METHOD: There were 24 subjects (18 men and 6 women) who were assessed for psychomotor performance during placebo and bupropion SR treatment in a double-blind cross-over in counter-balanced order. Each treatment arm lasted 5 wk. The daily bupropion SR dose was 150 mg during week 1, and 300 mg during weeks to 2 to 5. Subjects completed a drug side-effect questionnaire and were tested on two psychomotor test batteries once per week during each of the placebo and drug arms. RESULTS: There was no significant Impact of bupropion SR on serial reaction time, logical reasoning, serial subtraction, or multitask performance. With respect to drug side effects there was a main effect of drug on "number of awakenings" (p < 0.048), "difficulty returning to sleep" (p < 0.004), and "dry mouth" (p < 0.049). There was no impact of bupropion SR on dizziness. DISCUSSION: While we found some of the expected side effects due to bupropion SR, there was no effect on psychomotor performance. These findings support the possibility of returning aircrew to restricted flight duties (e.g., in non-fast jet aircraft) under close observation once stabilized on bupropion SR.

The impact of sertraline on psychomotor performance.

INTRODUCTION: Aircrew receiving treatment for depression are grounded during treatment and follow-up observation, generally amounting to at least 1 yr. Selective serotonin re-uptake inhibitors (SSRls) offer new treatment options for depression, of which sertraline (Zoloft) has the least imposing side-effect profile. There has been considerable interest in the possibility of returning aircrew to restricted flying duties once stablized on an SSRI with resolution of depression. This study was undertaken to determine whether or not sertraline effects psychomotor performance. METHOD: There were 19 volunteer non-depressed subjects (12 men and 7 women) who were assessed for psychomotor performance during placebo and sertraline treatment, in a double-blind cross-over protocol in counter-balanced order. Each treatment arm lasted 5 wk and involved ingesting one capsule each morning. The daily sertraline dose was 50 mg during week 1, 100 mg during week 2, and 150 mg during weeks 3, 4, and 5. Subjects completed a drug side-effect questionnaire and were tested on two psychomotor test batteries once per week, on the same weekday, at the same time of day throughout each 5-wk treatment period. RESULTS: There was no significant effect of sertraline on serial reaction time, logical reasoning, serial subtraction, or multitask performance. With respect to drug side effects, there was a main effect of drugs on "getting to sleep" (p < 0.002), "awakenings" (p < 0.007), "returning to sleep" (p < 0.001), "dry mouth" (p < 0.016), "nausea" (p < 0.001), "diarrhea" (p < 0.026), "tremors" (p < 0.005), and "sweating" (p < 0.016), as well as a drug x trials interaction for "drowsiness" (p < 0.012), "libido" (p < 0.039), and "difficulty with ejaculation" (p < 0.001). There was no effect of sertraline on dizziness. CONCLUSIONS: While we found some of the expected side effects due to sertraline, there was no effect on psychomotor performance. These findings support the possibility of selected use in aircrew and should be helpful in the ongoing aeromedical discussion about this evolving issue.