Sleep-wake disturbances in shift workers

INTRODUCTION — Individuals who work night shifts commonly experience difficulties with both sleep and alertness at desired times. Additionally, shift work is increasingly recognized as a risk factor for a variety of adverse health outcomes, including but not limited to cancer, metabolic syndrome, weight gain or obesity, cardiovascular disease, and pregnancy complications [1,2]. While some shift workers show circadian adjustment to their work schedule, many others do not. Those who do not adjust commonly experience excessive sleepiness during work hours and significant sleep disturbance.

It is estimated that one-third or more of shift workers experience sleep-wake disturbance and concomitant impairments of sufficient severity to meet criteria for shift work disorder.

The pathophysiology, clinical features, evaluation, and treatment of sleep-wake disturbances associated with shift work and shift work disorder will be discussed here. Other circadian rhythm disorders, such as jet lag and delayed sleep-wake phase disorder, are discussed elsewhere. (See "Jet lag" and "Delayed sleep-wake phase disorder".)

PATHOPHYSIOLOGY — Disturbances to sleep and impaired alertness in shift workers can be explained by disruptions to two biological processes, the homeostatic sleep drive and the circadian rhythm of alertness (figure 1):

●The homeostatic drive for sleep is dependent on time since the last sleep episode. As such, the need for sleep builds with sustained wakefulness and conversely, dissipates with sleep.

●Circadian rhythms refer to the 24-hour variations in biological functions. The circadian rhythm of alertness is readily apparent and, under usual circumstances, promotes wakefulness during the daytime and sleep at night. Circadian rhythms oscillate independently from sleep and external schedules but are calibrated and synchronized by a series of environmental cues, most important of which is natural sunlight or bright artificial light. The timing of light exposure can change the alignment between the endogenous circadian rhythm of alertness and external 24-hour day and, as such, is a critical factor in shift workers.

Under usual circumstances (ie, day workers), individuals go to bed when their sleep drive is high and their circadian signal for alertness is low (figure 1). However, the variability in sleep-wake schedules and timing of light exposure for individuals working nontraditional shifts (eg, night workers) often leads to misalignment between endogenous circadian rhythms and the timing of work and sleep periods. This misalignment between internal biology and externally imposed sleep-wake schedules will often lead to severely disrupted sleep and/or difficulty maintaining wakefulness.

As an example, night shift workers often attempt sleep during the day, when endogenous rhythms are promoting alertness. This conflict results in fragmented and restricted sleep, leading to excessive sleepiness and associated impairment during the wake period. In addition to severely reduced sleep duration, night workers are likely to be working at times when the circadian signal for alertness is minimal, resulting in poor work performance, impaired quality of life, and significantly elevated risk for driving accidents.

CLINICAL SPECTRUM

Sleep disturbances — Both sleep duration and sleep quality are commonly affected in shift workers. Shift workers generally report 30 to 60 minutes less sleep compared with day workers [3-5], and individuals with shift work disorder (SWD) report even greater reductions in sleep, with an average decrease of approximately 90 minutes [6]. Sleep restriction may be compounded by family and social obligations [7].

The degree of sleep disruption may vary by type of shift work and whether the schedule is rotating or fixed. Working nights on a rotating basis has greater negative effects on sleep length than permanent night shifts, and working overnight shifts is typically more disruptive to sleep than either early-morning or evening shifts [5]. When shifts are rotating, most individuals are better able to adjust to forward-rotating shifts (ie, morning, then afternoon, then overnight), particularly if the speed of rotation is slower (>4 days per shift assignment) [8-10]. In a cohort study of 144 nurses working either forward- or backward-rotating shifts, both schedules were associated with adverse performance, but levels of sleepiness and decrements in vigilance and reaction time were greater among those on a backward-rotating schedule [9].

Shift workers experience a range of sleep difficulties, including difficulty falling asleep, fragmented sleep, poor sleep quality, and reduced sleep duration. Shift work can also be a precipitating factor for insomnia or exacerbate pre-existing insomnia symptoms. In a large epidemiological study, 19 percent of night workers reported clinically significant insomnia, which was more than twice the reported rate in day workers [6]. Insomnia has been associated with adverse functioning in workers, including increased absenteeism, reduced work productivity, and increased injuries and illnesses [11].

Symptoms during wakefulness — During waking hours, shift workers are prone to excessive sleepiness, decreased cognitive and psychomotor function, and poor emotional regulation.

●Sleepiness – At least two-thirds of shift workers report excessive sleepiness, though not all exhibit significant impairments (approximately one-third meet criteria for shift work disorder) [12,13]. A subset of these sleepy workers report accidental dozing during work [14-16], sometimes with fatal consequences, as night-shift workers are often involved in safety-sensitive occupations.

●Cognition – Sleepiness impairs a range of cognitive functions, including vigilance, cognitive flexibility, error detection and correction, processing speed, logical reasoning, learning, and creativity [17-24].

●Psychomotor function – Performance on tasks requiring psychomotor control, such as high-precision tasks and driving, are often adversely impacted in shift work [22,25].

●Social and affective function – Chronic sleep restriction in shift workers may lead to affective instability [26]. Sleep-deprived brains are less able to regulate emotions, particularly those that have a negative valence [27]. In other words, shift workers may experience stress more intensely, which is further exacerbated by impaired stress management due to sleep and scheduling difficulties.

Accidents and errors — In combination, these impairments can increase risk for accidents, injury, and even death [28]. Shift workers are at increased risk for impaired driving, including falling asleep at the wheel [25]. This may be particularly relevant for night and early-morning shift workers, who are mostly likely to be commuting during times of extreme sleepiness [29]. (See "Drowsy driving: Risks, evaluation, and management".)

Adverse events related to shift work in medical personnel include increased diagnostic and medication errors and increased rates of patient death [30,31]. In one study, rotating shift workers were found to have twice as many work-related accidents compared with day workers [32]. In another study of medical interns, the relative risk of percutaneous injuries was approximately 60 percent higher in night-shift interns compared with day-shift interns [33].

Adverse health outcomes — Shift work has been associated with a variety of adverse health outcomes [34-42]. A meta-analysis of 34 observational studies that included over 2 million people found small but significant associations between shift work and myocardial infarction (risk ratio [RR] 1.2) and ischemic stroke (RR 1.05) [37]. Other studies have reported an increased risk of obesity (odds ratio [OR] 3.9) [43,44], diabetes (RR 1.1 to 1.4) [45], and inflammation [46].

Accumulating evidence also supports an association between shift work and increased cancer risk [1,41,47-52]. Shift work with circadian disruption has been recognized as a probable carcinogen by the World Health Organization since 2007 [47].

EVALUATION AND DIAGNOSIS — Essential aspects of the evaluation include a sleep history, safety risk assessment and sleep logs and/or actigraphy when possible [53]. Polysomnography is only necessary if there is clinical suspicion for obstructive sleep apnea (OSA) or other sleep disorders that may be contributing to poor sleep.

History — Evaluation of sleep-wake disturbances in shift workers should include an assessment of work history (eg, occupation, work schedule, years of shift work), a detailed sleep history (including daytime and nighttime sleep difficulties), level of sleepiness using standardized measures (calculator 1), accidental dozing (particularly while driving), and any performance impairment during work shifts. Patients should be asked about sleep hygiene (table 1) and use of medications or substances that may impact sleep (table 2).

The history should also probe for symptoms of comorbid sleep disorders, such as OSA, narcolepsy, restless legs syndrome/Willis-Ekbom disease, and parasomnias. This includes questions about loud or habitual snoring, witnessed pauses in breathing during sleep, cataplexy, hypnagogic hallucinations or sleep paralysis, an uncomfortable urge to move the legs, and abnormal movements or behaviors during sleep. The clinical features and diagnosis of these disorders are reviewed separately. (See "Clinical presentation and diagnosis of obstructive sleep apnea in adults" and "Clinical features and diagnosis of narcolepsy in adults" and "Clinical features and diagnosis of restless legs syndrome and periodic limb movement disorder in adults", section on 'Periodic limb movements of sleep'.)

Validated questionnaires for the assessment of sleep-wake disturbances are useful to better characterize symptom severity and follow symptoms over time. The Insomnia Severity Index (ISI) is commonly used for assessing sleep disturbances and can be applied separately for nighttime versus daytime sleep [54]. A score of ≥10 on the ISI is indicative of clinically significant insomnia. The Epworth Sleepiness Scale is also validated and commonly used for assessing excessive sleepiness (calculator 1), with a score ≥10 indicative of excessive sleepiness [55].

Circadian preference may be assessed clinically or with validated questionnaires, and used as a supplement to inform interventions. Circadian preference, or chronotype, refers to the extent to which individuals have a morning preference (ie, "morning lark" or early chronotype) versus a nocturnal preference (ie, "night owl" or late chronotype). A mismatch between chronotype and shift type (eg, an early chronotype working the night shift) is associated with worse adaptation to shift schedule [56]. The Munich Chronotype Questionnaire for Shift Workers (MCTQShift) is validated for shift workers and yields a continuous measure of chronotype based on sleep behavior [57,58]. Information on chronotype may inform treatment strategies (eg, support in adjusting to shift work versus terminating shift work), particularly for individuals with extreme chronotypes.

Sleep diary — Use of a sleep diary is a mainstay for characterizing sleep-wake disturbances related to shift work. Sleep diaries provide more reliable details than retrospective self-report to distinguish sleep-wake rhythms on work days, off days, transition to work days, and transition to off days. Information from sleep diaries can also be summarized quantitatively, such as average sleep efficiency, sleep-onset latency, wake timing following sleep onset, frequency of night awakenings, and sleep quality. These variables can then also be used to monitor treatment response.

A sleep diary should be completed prospectively for two weeks [59]. Either the 24-hour (form 1) or the consensus sleep diary (table 3 and table 4) can be used. The 24-hour diary depicts timing of sleep and wake across multiple days, which increases the ease of visual pattern detection. Conversely, the consensus sleep diary is preferred for the evaluation of insomnia. Some patients may also use a mobile application to log sleep diaries.

Actigraphy — Actigraphy is recommended as a supplement to sleep diaries when possible because it does not rely on self-report, and may also be used as an estimate of circadian phase. Actigraphy is also a viable alternative to sleep logs in patients who have difficulty with completing a sleep diary, or when there are inconsistencies between symptom presentation and self-reported sleep.

Actigraphy is usually obtained via a wrist-worn device, placed on the nondominant hand, that measures movement and (with some models) light exposure (figure 2). Actigraphy can be paired with sleep diaries (table 3 and table 4) and has been shown to be comparable to polysomnography (PSG) for evaluation of total sleep time [60]. Actigraphy can also be a useful outcome measure in evaluating response to treatment. Attention should be directed to both daytime and nighttime sleep. (See "Actigraphy in the evaluation of sleep disorders".)

Prediction of dim light melatonin onset (DLMO) as a marker of circadian phase (and thus circadian misalignment) has also been tested using actigraphy data processed through a mathematical model of the human circadian system [61]. Light and activity data from research-grade actigraphs can be uploaded into a web-based calculator to produce estimates of DLMO [62].

Consumer-based wearable technologies have not been validated in a clinical sample of shift workers, but the crude sleep-wake information they provide may nonetheless have some clinical utility. Clinicians should be aware that the data collected may have lower accuracy compared with clinical- or research-grade actigraphs. (See "Actigraphy in the evaluation of sleep disorders", section on 'Consumer wearable devices'.)

Polysomnography — PSG is not required unless there is clinical suspicion for OSA or other sleep disorders. Nonetheless, comorbid sleep disorders in night workers are relevant and critical to diagnose, because interventions that aim to appropriately realign a shift worker's circadian phase with their work schedule will not adequately address other potential sleep disorders that are contributing to sleep disturbances or sleepiness.

If performed, PSG should ideally be timed to match the individual's longest or least disturbed usual sleep time (whether during the day or night). (See "Overview of polysomnography in adults".)

Diagnostic criteria — Shift work disorder is defined in the third edition of the International Classification of Sleep Disorders (ICSD-3) as follows [53]:

●There is a report of insomnia and/or excessive sleepiness, accompanied by a reduction of total sleep time, which is associated with a recurring work schedule that overlaps with the usual time for sleep.

●The symptoms have been present and associated with the shift work schedule for at least three months.

●The symptoms cause clinically significant distress or impairment in mental, physical, social, occupational, education, or other important areas of functioning.

●Sleep log and actigraphy monitoring (whenever possible and preferably with concurrent measurement of light exposure) for at least 14 days (work and free days) demonstrate a disturbed sleep and wake pattern.

●The sleep and/or wake disturbance are not better explained by another current sleep disorder, medical or neurologic disorder, mental disorder, medication use, poor sleep hygiene, or substance use disorder.

MANAGEMENT — Interventions for sleep-wake disturbances in shift workers include both nonpharmacologic and pharmacologic strategies. Treatment should be individualized and tailored to a patient's specific circumstances and needs. That said, it is common practice to approach treatment in a stepwise fashion, focusing first on improving daytime sleep and then addressing residual complaints of sleepiness or impaired function during the night shift. Safety should always be prioritized in treatment strategies.

More limited data on circadian realignment strategies using bright light and/or melatonin suggest that these interventions may also be worth trying in motivated patients. (See 'Circadian re-alignment strategies' below.)

Counseling and education — Prior to engaging in symptomatic management, patients with shift work disorder (SWD) should understand that elimination of shift work should resolve symptoms, and therefore a change in work schedule should be considered as an option when possible. Since implementation of such changes may be limited in the workplace, it may help to provide a letter on the patient's behalf, explaining the disorder and its consequences.

Sleep scheduling — A regular sleep schedule that can be followed even during off-work periods is encouraged in order to promote stability in circadian entrainment. This may need to be individualized, as shift workers often require flexibility in order to meet varying social and family obligations.

While a consolidated seven to nine hours of sleep is recommended, daytime sleep can be separated into two bouts in order to accommodate the need for flexibility: the first, a regularized three- to four-hour "anchor" sleep that takes priority, and a second bout that can vary around other responsibilities (total sleep should fall between seven to nine hours (figure 3)).

Improving daytime sleep — Shift workers who are experiencing sleep-wake disturbances of any level of severity can benefit from interventions aimed at improving daytime sleep. The initial approach involves review of environmental and scheduling factors to promote better sleep (ie, sleep hygiene). For patients with persistent difficulties obtaining adequate sleep, options include use of a short-acting hypnotic agent and exogenous melatonin [59]. The choice among these depends on availability and cost, presence of contraindications, and patient preference.

Sleep hygiene — The sleep environment should be modified to promote consolidated daytime sleep, with particular attention to light, temperature, and noise level (table 1).

Light-blocking shades should be used to reduce as much sunlight as possible, with cool ambient temperature (generally between 60 to 75°F). If ambient noise cannot be controlled, a white noise machine may help reduce arousals that are due to variability in environmental noise.

Hypnotics — For patients who have difficulty initiating daytime sleep at the desired time despite optimal sleep hygiene, a short-acting benzodiazepine receptor agonist or orexin receptor antagonist can be used to promote daytime sleep [59]. The risk of carry-over of sedation effects into the night shift should be discussed with individuals who are considering pharmacotherapy, particularly if longer-acting medications are used. Residual sedation is a common side effect, particularly with sleep periods shorter than seven hours, and careful monitoring of potential adverse events is critical in shift workers due to the increased prevalence of excessive sleepiness in this population. Dosing and administration of medications for insomnia is reviewed in detail separately. (See "Pharmacotherapy for insomnia in adults".)

Limited studies in shift workers have demonstrated improvements of 30 to 60 minutes in daytime sleep with use of short-acting nonbenzodiazepines such as zolpidem and short- or intermediate-acting benzodiazepines such as triazolam and temazepam [59,63,64]. A small pilot trial also supports the efficacy and tolerability of suvorexant, an orexin receptor antagonist, in this setting [65]. However, it is important to recognize that use of hypnotics may not eliminate excessive sleepiness, especially in patients with circadian misalignment. In such cases, realignment of circadian rhythms to match the sleep-wake schedule using bright artificial light exposure is critical. (See 'Circadian re-alignment strategies' below.)

Exogenous melatonin — A meta-analysis of seven small randomized trials of melatonin versus placebo in night workers (n = 263) found evidence that exogenously administered melatonin (1 to 3 mg) improves total sleep time [66]. However, the quality of the evidence was limited by small samples sizes, variability in dosing, and duration of treatment.

When exogenous melatonin is used to promote daytime sleep in shift workers, doses of no more than 1 to 3 mg should be used, taken 30 minutes prior to the desired onset of sleep [59].

Similar to use of hypnotics, use of melatonin is unlikely to normalize alertness during the night shift, and patients often require additional strategies to maximize circadian adaptation. (See 'Improving wakefulness during the night shift' below.)

Cognitive behavioral therapy for insomnia — Cognitive behavioral therapy for insomnia (CBT-I) is an effective treatment for chronic insomnia [67]. More limited data support the use of CBT-I adapted for SWD. Instead of sleep restriction, CBT-I in SWD focuses more on sleep scheduling and includes use of specifically timed exposure to sunlight or artificial bright light [68-70].

Improving wakefulness during the night shift — Optimizing daytime sleep does not typically eliminate sleepiness during the night shift [71,72]. For patients who are symptomatic despite adequate or optimized daytime sleep, countermeasures include short naps before or during the shift, caffeine, or use of a wake-promoting agent such as modafinil or armodafinil [73].

Naps — For individuals who have the flexibility to schedule naps just before or during a shift, evidence indicates that naps before or during the night shift may improve alertness and performance [59,74-79]. For safety critical operations, naps can be limited to under 60 minutes to minimize the chances of entering deep sleep and to reduce disorientation from sleep inertia upon awakening [80]. Naps may be planned prior to the shift or late in the shift to improve alertness and performance.

Caffeine — Caffeine can be used to enhance alertness during the night shift, though care must be taken in the timing of use to avoid impairing daytime sleep [59]. Small doses of caffeine (approximately 75 to 100 mg, the average amount in a small cup of coffee) administered intermittently throughout the night shift may help sustain alertness [66,81]. Supporting data for caffeine include a randomized trial in 56 shift workers showing that naps in combination with caffeine reduced workplace sleepiness and improved work performance [74].

Caffeine use should be limited to the first half of the night shift (no caffeine within eight hours of bedtime), and evidence suggests that single doses of at the beginning of a night shift may be more alerting than divided doses [82]. Risks of caffeine use include disrupted daytime sleep, particularly if ingested close to bedtime. If used therapeutically, social use of caffeine may need to be restricted in order to avoid tolerance.

Wake-promoting agents — The wake-promoting agents modafinil and armodafinil are options in patients with persistent sleepiness in conjunction with nonpharmacologic measures to improve sleep and alertness. Treatment decisions should be individualized, taking into account the severity of symptoms and the potential consequences of impaired alertness (which may vary based on job responsibilities) and the risk of side effects. Both agents are approved for this indication by the US Food and Drug Administration (FDA) but not by the European Medicines Agency.

There is evidence that wake-promoting agents such as modafinil and armodafinil improve alertness during shift work. The magnitude of benefit may vary among individuals, with some studies finding relatively modest effects [59,66] and others showing normalization of alertness to within daytime levels [83]. In two randomized trials of patients with shift work disorder (n = 572), armodafinil (150 mg taken 30 to 60 minutes before the night shift) improved subjective sleepiness by one point on the Karolinska Sleepiness Scale and improved alertness compared with placebo [66,84,85]. In a separate small randomized trial, armodafinil also improved performance on a driving simulator compared with placebo [24]. Modest but statistically significant benefits have also been observed with modafinil (200 mg) in shift workers [86].

The most common side effects of modafinil and armodafinil are headache and nausea; postmarketing surveillance studies have reported rare cases of Stevens-Johnson syndrome in association with modafinil [87].

Circadian re-alignment strategies — Specifically timed exposure to bright light (2000 to 10,000 lux at the cornea) has the potential to lessen the mismatch between an individual's internal circadian phase and the desired or environmental schedule, and limited data have indicated that such interventions may be useful in shift workers to improve alertness. However, additional studies are needed to demonstrate the feasibility and real-world effectiveness of these strategies [88]. Timing of light should be based on an individual shift worker's phase markers (eg, dim light melatonin onset [DLMO]) whenever possible. (See 'Actigraphy' above.)

●Light exposure – Bright light exposure is effective at various doses, ranging from as low as four 20-minute periods during breaks to as much exposure during the shift as possible [59]. Light may serve to improve alertness and shift circadian rhythms to realign internal biology with the externally-imposed sleep-wake schedule. When used appropriately, each hour of exposure to bright light should incur a 30- to 60-minute shift in the biological clock.

●Light-blocking glasses – When a delay in circadian rhythms is desired (night/evening work), light-blocking glasses in the morning (approximately 6:00 to 11:00 AM) can be helpful in adjusting rhythms, especially in shift workers who would otherwise be exposed to sunlight before their scheduled daytime sleep period. Similarly, light-blocking shades should be installed in the sleeping environment to prevent exposure to sunlight during daytime sleep. (See 'Sleep hygiene' above.)

Safety issues — Very often shift workers are employed in safety-sensitive or transportation occupations, and excessive sleepiness and accidents should be discussed and monitored throughout treatment (see 'Symptoms during wakefulness' above). The Epworth Sleepiness Scale (calculator 1) can be helpful in tracking risk and response to treatment in a standardized way.

Drowsy driving should be assessed, including any history of vehicular accidents or near-misses attributable to sleepiness, fatigue, or inattention. Behavioral methods of reducing such risks should be reviewed with the patient and with family members, when possible, including the safest option of arranging for a ride home after a night shift. (See "Drowsy driving: Risks, evaluation, and management".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Parasomnias, hypersomnias, and circadian rhythm disorders".)

SUMMARY AND RECOMMENDATIONS

●Symptoms and risks – Individuals who work night shifts commonly experience difficulties with both sleep and alertness at desired times. They are at risk for impaired psychomotor, cognitive, social, and emotion function and a variety of adverse health outcomes, including diabetes, cancer, and cardiovascular disease. (See 'Clinical spectrum' above.)

●Prevalence – Up to one-third of shift workers report regular, persistent complaints of insomnia and/or excessive sleepiness that meet formal criteria for shift work disorder (SWD). (See 'Diagnostic criteria' above.)

●Evaluation – Clinicians should perform a comprehensive sleep history, risk assessment, and objective assessment of sleep-wake patterns. Sleep logs (table 3 and table 4) and actigraphy are the primary tools used to objectively determine sleep-wake patterns over an extended period (ideally two weeks). (See 'Evaluation and diagnosis' above.)

●Approach to improving sleep

•Sleep scheduling – Minimum measures to improve sleep after a night shift include a regular sleep schedule (ie, anchor sleep), light-blocking shades, and ambient noise control. If family or social responsibilities prohibit one seven- to nine-hour sleep period, a regularized three- to four-hour morning "anchor" sleep with a second variably timed sleep period is recommended. (See 'Sleep scheduling' above and 'Improving daytime sleep' above.)

•Medications – For individuals who desire pharmacologic therapy to help achieve adequate sleep, we suggest use of a short-acting benzodiazepine receptor agonist (eg, zolpidem, temazepam) (Grade 2C). Melatonin and the newer orexin receptor antagonists are reasonable alternatives. (See 'Hypnotics' above and 'Exogenous melatonin' above.)

Risks of carry-over sedation should be discussed and monitored when any hypnotic is used. Importantly, optimizing daytime sleep does not eliminate sleepiness during the night shift, and additional measures are needed to mitigate the risk for accidents, particularly in patients with circadian misalignment.

•Cognitive behavioral therapy – Behavioral strategies to improve sleep in shift workers include sleep scheduling (including naps) and cognitive behavioral therapy. (See 'Cognitive behavioral therapy for insomnia' above.)

●Countermeasures to mitigate sleepiness

•Naps and caffeine – Naps (less than one hour) before and during the night shift can improve alertness; caffeine intake during the shift can also help. (See 'Naps' above and 'Caffeine' above.)

•Medications – For individuals with excessive sleepiness during night shifts who desire pharmacotherapy, we suggest armodafinil or modafinil (Grade 2B). The observed benefits in randomized trials have been modest, however, and side effects may outweigh benefits in some patients. (See 'Wake-promoting agents' above.)

●Safety – Shift workers are at greatest risk of accidents during night and early morning shifts when circadian alertness is minimal. These and other safety issues should be reviewed with patients regularly. (See 'Safety issues' above.)