Clinical manifestations

Presentation and course

Shift work sleep disorder is characterized by insomnia or excessive sleepiness accompanied by a reduction in total sleep time in individuals with recurring work schedules that overlap with the usual time for sleep, with symptoms lasting at least 3 months as documented on a 14-day recording of sleep log or actigraphy (02). The boundary between a normal and a pathological response to the circadian stress of the desynchronization of the sleep-wake schedule with the natural time clues may be difficult to determine. Most of the medical disability due to shift work occurs in night or early morning shift workers, yet rotating shifts are also associated with sleep issues. Shift workers may develop one or more of the following: (1) shortened and interrupted sleep in the daytime after the night shift, (2) compelling sleepiness at work, (3) sleepiness when commuting home after the work shift, and (4) difficulty initiating and maintaining sleep on nights off from work. However, data suggest that even those that appear to be adapting well may have more subtle medical issues, such as metabolic issues and mood disturbance.

Surveys show that permanent night workers average 6 hours of sleep on workdays, about 1 to 4 hours less than the average day or evening shift worker; rotating shift workers average even less sleep (about 5.5 hours) when on the night shift. Night-shift workers differ in their strategy of obtaining daytime sleep. The majority have their major sleep period after returning from work (eg, 9:00 AM to 4:00 PM), some sleep in the afternoon (eg, 2:00 PM to 9:00 PM), and still less split their sleep into two periods with the longer sleep period in the morning (eg, 9:00 AM to 2:00 PM and 7:00 PM to 9:00 PM). The individual choice depends on family and social circumstances. However, the major concern is chronic sleep deprivation due to repeated attempts to sleep at an unfavorable phase of the circadian rhythm. This results in impaired performance while awake, along with greater psychosocial and mood problems. Neurophysiologic deficits in attention have been demonstrated in poorly adjusted night workers versus well-adjusted night workers (24). Nearly 62% of night shift workers complain of short sleep duration, 30% complain of poor sleep quality, and 36% note impaired activities of daily living, compared to 19%, 36%, and 24.8% of all workers, respectively (82). Throughout this multivariate analysis, night shift workers had the highest likelihood of developing these sleep problems.

Shift work may present with other brain and somatic effects. Rotating shift work is associated with an increase in systolic blood pressure, and working permanent night shifts is associated with increases in both systolic and diastolic blood pressure (22). In addition to the association between shift work and weight gain, concern has been raised over the development of metabolic syndrome. A meta-analysis of 38 observational studies,10 cohorts, and one nested case-control study showed that shift work increases the likelihood of metabolic syndrome by an adjusted odds ratio of 1.11 (34). Night shift workers also have a greater likelihood of experiencing esophageal reflux and gastrointestinal-related symptoms (16). A study of nurses working night shift show increased prevalence of sleep disorders, digestive (changes in appetite, constipation, and ulcers) disorders, and mood issues (anger and depression), leading to greater difficulty in personal issues (83). These mood symptoms are more likely associated with sleep issues and shift work disorder (11) Chellappa and colleagues showed that mood issues can present within 4 days of the circadian misalignment (12). The mood issues in shift work appear to extend to decreased social functioning and quality of life (41). The circadian misalignment effect on mood appears to ultimately affect longer-term mental health (76). Beyond mood issues, shift work appears to have effects on attention, memory, and response inhibition (37). Thus, some patients who have difficulty with shift work may seek medical help for symptoms appearing unrelated to sleep.

Prognosis and complications

Emerging evidence suggests that appropriately functioning circadian rhythms contribute to well-being and health and cognitive performance (49). Shift work sleep disorder is associated with a greater risk of gastrointestinal problems, cancer, depression, heart disease, excessive sleepiness, and accidents as well as decreased productivity. Shift workers are found to have greater complaints of reflux, peptic ulcer disease, and irritable bowel syndrome (16; 31; 38). Increasing evidence relates circadian desynchrony to disorders such as metabolic syndrome--insulin resistance, high blood pressure, central obesity, decreased high-density lipoprotein (HDL) cholesterol, elevated triglycerides--and cardiovascular events (34). Lim and colleagues showed that night shift work nearly doubled the risk of developing metabolic syndrome (39). A subsequent meta-analysis suggests that the effect is not as robust as once thought but is still significant (34). Yet, shift workers appear to have an increased risk of diabetes and metabolic syndromes that are primarily due to circadian misalignment that appears to be related to the interference of the sleep-wake cycle and eating patterns, leading to these pathophysiological changes (59; 57), and this risk is higher in women (61). Shift workers may bear a higher risk of hypertension and ischemic heart disease compared to day workers, particularly those on rotating shifts (33; 46). The risk of elevated blood pressure may be related to the type of shift work; rotating shift work appears to have more of an effect on systolic pressure, and permanent night shift work increases both diastolic and systolic pressure (22). The long-term effects of shift work include an increased risk of dying. In a meta-analysis of 16 cohort studies, Su and colleagues showed that cardiovascular, all-cause, and, to a lesser extent, cancer-related mortality were increased with shift work (67). In part, some of the risk may be from longer hours at work and shorter sleep, but an increase in C-reactive protein and blood pressure appears to be related to circadian disruption (14; 44). Poor sleep related to shift work positively correlates with increased inflammatory markers, and poor sleep is positively associated with systolic and diastolic blood pressure increases regardless of the level of inflammatory markers (32). Shift work in adolescence has also been implicated in increasing the risk for immune issues, such as multiple sclerosis (27).

The link to cancer has been more debatable (56). Multiple signaling and metabolic pathways accelerate tumor growth in those with circadian desynchronization. Additional work also suggests that circadian desynchronization may alter DNA repair, increase oxidative damage to DNA, and influence immunological signaling (06; 79). Similarly, night shift work may cause a shortening of telomere length and is suggested as a mechanism for the increased risk of breast cancer (55).

Epidemiological studies looking for the link to cancer have suggested that breast and endometrial cancer may be linked to shift work, but this link is controversial and does not appear to be uniform across all types of cancers (56). Earlier epidemiological evidence suggested a link of shift work to cancer and the International Agency for Research on Cancer (IARC) classification of shift work as a probable human carcinogen. Subsequent meta-analysis has been conflicting and has led to greater refinement in studies examining the linkage (72; 35). In a systematic review of several meta-analyses, Rivera and colleagues found moderate-grade evidence to support a link to breast cancer (52). Other cancers appear less likely to have this linkage. Gan and colleagues found a nonlinear relative risk of 1.23 linking shift work to prostate cancer in Asian men (23). Walasa and colleagues showed that shift workers did not have a higher incidence of colon cancer, raising the question of which tumor types may be more likely to emerge after long-term circadian disruption (75).

Shift work appears to increase the likelihood of poor mental health. In a meta-analysis of seven longitudinal studies including 28,431 participants, Torquati and colleagues showed that, particularly for women, shift work increased the risk of depression (71). In addition to the increased risk of developing depression, nurses involved in shift work were also more likely to develop anxiety (09). Other complications include alcohol or drug abuse in an attempt to improve daytime sleep, increased rates of accidents due to impaired alertness at work or during commute, depression, malaise, personality changes, and problems with interpersonal relationships. The sum of many of these symptoms is associated with a poorer quality of life for individuals performing shift work (41). These complications may develop gradually or abruptly in a worker who has previously tolerated shift work well, as shift work tolerance seems to decrease with age.

Shift work may complicate the course and management of asthma, diabetes, epilepsy, and other disorders that have circadian rhythm components in their pathophysiology and response to treatment and are best managed with a highly regular medication schedule that may be difficult to achieve in a patient whose work schedule is highly irregular. The risk of shift work and poor sleep impairing recovery was demonstrated in patients with cardiovascular disease (05). Patients sleeping less than 6 hours per night or working night shift three nights per week had greater risk of recurrent cardiac events. Furthermore, in an analysis of two Swedish long-term studies of twins, Bokenberger found that APOE ɛ4 carriers exposed to more than 20 years of shift work had an increased risk of dementia (07). These studies suggest that long-term shift work may have significant effects on the body and brain.

Long-term, most individuals revert back to nocturnal sleep after discontinuing working night shifts. However, some may have long-term difficulty with their sleep. These individuals may benefit from evaluation and management of their sleep complaints by a sleep specialist.

Clinical vignette

A 46-year-old line mechanic was promoted to a lead position on the night shift that worked 5 out of 7 days of the week. He noted that soon after taking the position he had difficulty falling asleep during the day and eventually had difficulty staying alert during the night. On his days off he would stay awake during the day to be with his family and then have difficulty falling asleep at night. After 3 months on the job, his wife noted he was “grumpy” all the time, and he started gaining weight. He also noted that he had difficulties with his stomach and that he had periods of constipation and loose stools. After 6 months he described malaise, anxiety, and decreased enjoyment in doing his hobbies. The patient had gained over 15 pounds and developed elevated blood pressure. The patient had tried melatonin and coffee without success and now noted that several shots of bourbon would help him sleep for a short period during the day. He asked about using a stimulant to help with his work but was afraid to use it given a family history of heart disease.

The patient was advised to wear dark sunglasses on his way home from work and to utilize melatonin 1 mg to help him lengthen his sleep when he came home from work. He also tried minimizing shift in his circadian rhythm by going to bed at 3 AM on his non-work nights and sleeping until 11 AM but reverting to a bedtime of 8 AM and waking at 4 PM for his typical workdays. Evening light exposure, as well as cognitive behavioral therapy for insomnia, was introduced to improve nighttime wakefulness and daytime sleep. The patient also tried modafinil 200 mg to help with his alertness during work. After 6 months, the patient noted some benefit but still had significant complaints regarding his sense of well-being and requested a transfer to a day shift position. On moving to the day shift the patient had some difficulty with disturbed sleep for several months. These symptoms improved with further circadian rhythm reinforcement and strict wake time for the work and non-workdays.

Biological basis

Etiology and pathogenesis

The circadian rhythm is designed to help the body anticipate and ready itself for upcoming biological needs. Examples include the rumbling of the stomach before routine mealtime or the finding that exercise comes easier in the afternoon. Rapid adjustment of a schedule does not translate to an adjustment of the clock. Therefore, the body has limited ability to adjust to dramatic swings related to shift work. Thus, shift work disorder is linked to misalignment of the voluntary sleep-wake cycle to the natural circadian rhythm, producing a circadian rhythm that is prepared for waking activities when the worker is attempting to sleep and sleeping activities when the worker is awake. This process then creates sleep disruption of several systems most notably sleep disturbance that has additional downstream effects related to sleep deprivation and fragmentation. Similarly, the lack of push for alertness from the circadian drive is lowest during the night shift, resulting in impaired performance, memory, coordination, and other cognitive attributes. In addition to the sleep-wake cycle disruption, shift work involves enforced voluntary dissociation of the other hormonal, autonomic, and metabolic rhythms that occur on the basis of the circadian rhythm. These circadian rhythms mostly remain synchronized with the “natural” light-dark cycle, even after years of night shift work, and do not yield easily to the shifted sleep-wake cycle.

The circadian rhythm serves to prepare the body for anticipated events such as wakefulness, feeding, and physical activity (04). As the master clock, the suprachiasmatic nucleus is responsible for coordinating and synchronizing the circadian rhythm throughout the body. The paired suprachiasmatic nuclei of the anterior hypothalamus have been established as the site of the mammalian circadian oscillator. This grouping of about 10,000 anterior ventromedial hypothalamic neurons manifests a high amplitude circadian pattern of firing both in intact, freely behaving animals and in vitro. The SCN “master clock” is composed of multiple single cell circadian oscillators that, when synchronized, generate coordinated circadian output that regulate peripheral “clocks” by transmission of circadian timing signals. This regulation is achieved by means of direct and indirect projections to other regulatory brain areas, modulating in turn their circadian outputs and coordinates other overt rhythms (eg, arousal, hormonal secretion, temperature, feeding, etc.). Daily behavioral, vegetative, and circadian firing rhythms of other brain regions disappear if the SCN are lesioned and some, but not all, are restored with fetal brain tissue transplants into the anterior third ventricle.

The suprachiasmatic nucleus, like many organs, utilizes a multi-looped feedback system of genetic transcription and a nuclear and cellular protein system that oscillates at approximately 24 hours. Even though 7% to 12% of genes fluctuate in a circadian fashion, the essence of this clock resides in the genetic transcription of the Clock and Bmal1 genes (04). Once transcribed, these form a protein heterodimer that binds and activates E-box sequence promoters that positively influence the transcription of Period (Per 1, 2, and 3) and cryptochromes genes (Cry1 and Cry2). The protein products of the Period and cryptochrome genes dimerize and feedback negatively on the transcription of Clock and Bmal1 genes, creating the circadian rhythm. This rhythm is not exactly 24 hours; therefore, the clock must be adjusted by environmental time clues. The most powerful time clue is bright light, but food, social interactions, and activity also appear to influence the phase of the biological clock. The suprachiasmatic nucleus synchronizes the peripheral circadian rhythm clocks by utilizing melatonin, in addition to the endocrine and autonomic nervous system outputs. As every cell in the organism has active molecular oscillators, the inherent circadian cyclic genes’ expression optimizes each organ’s performance for the anticipated task at that predicted time. In the absence of a central master clock, the myriad peripheral pacemakers would produce disorganization of rhythms and loss of optimal coordinated function.

The biological clocks of normal humans of all ages have a natural endogenous circadian cycle of slightly more than 24 hours, generally about 24.2 hours. If all temporal cues (zeitgeber, German for “time givers”) are removed, this cycle induces other rhythms that are progressively phase delayed relative to the external clock time. Therefore, the internal body clock must be adjusted on a daily basis to align with the external 24-hour day, a process called entrainment. Entrainment involves using zeitgebers (German for “time givers”) to reset the internal clock slightly each day. Common zeitgebers include light, melatonin, food intake, social interaction, and exercise. Each of these factors can independently change the timing of the circadian pacemaker, thereby altering the time of all physiologic processes that are regulated on a circadian basis.

Light is the main zeitgeber for endogenous clocks in humans. The human circadian system is more sensitive to short-wave blue-green light than to long-wave red-spectrum light. The major afferent input to the SCN consists of a melanopsin containing subset of photosensitive retinal ganglion cells whose axons synapse on SCN cells. This retinohypothalamic tract transmits nonvisual, light-dark information to the SCN, which is mediated through glutamate and pituitary cyclase-activating peptides. In addition to a direct pathway, retinal ganglion cells also project to the intergeniculate leaflet (located within the lateral geniculate body), which projects to the SCN. Neuropeptide Y and GABA are the main output neurotransmitters. Other time clues appear to influence the SCN through the use of serotonergic fibers from the brainstem raphe nuclei.

Key to understanding the zeitgebers is that the response of the circadian rhythm depends on when the stimulus is delivered. For example, light delivered prior to the temperature nadir (typically 4:00 AM) will cause a delay in the body clock. Light delivered after the body temperature nadir will advance the clock. Thus, for light therapy to be appropriately used, understanding the true timing of the circadian rhythm is essential. For light, the amount of maximal daily resetting is limited to 1 to 3 hours, and the magnitude of response plotted against the circadian time will produce a phase response curve that indicates the circadian times of maximum effect of the zeitgeber.

Similar to light, melatonin also has a time-dependent effect on the phase of the circadian rhythm. However, melatonin has the opposite effect of light, so that melatonin delivered in the afternoon and evening causes a phase advance whereas morning use may cause a mild phase delay (17). The suprachiasmatic nuclei exhibit dense melatonin receptors, probably establishing a feedback mechanism for the sleep-wake cycle. The role of melatonin in the human circadian cycle is modulatory. Both SCN entrain to melatonin and potentially other factors such as light that help synchronize the multitude of endogenous rhythms in the brain and other organs (04). Melatonin is produced during darkness periods and is suppressed by light of sufficient duration and intensity, but melatonin also has its own endogenous rhythm in which the peak occurs during the evening several hours prior to nadir of core body temperature. The melatonin circadian rhythm is highly robust, has low intra-individual but high inter-individual variability, and is appreciably masked only by light. The dynamics of the daily duration of melatonin secretion is significant in seasonal and reproductive physiology in animals; longer nights characteristic of the winter photoperiod are signaled by longer melatonin secretion duration. DLMO is the most popular marker of the circadian phase. The phase of the circadian melatonin rhythm can be reset by appropriately timed light pulse; phase-response curve describes the effect of light on the amplitude and direction of the melatonin rhythm phase shift.

Other nonphotic signals may help change the phase of the peripheral circadian rhythm. Exercise plays a role in the circadian rhythm through the information of arousal stimuli influencing the central clock and also local clocks in peripheral tissues (69). Similarly, mealtimes may influence the genetic expression of the circadian rhythm (26), and specific timed meals may play a role in synchronization of peripheral clocks. This differential effect was demonstrated by Wehrens and colleagues who found that specific timed meals could have little effect on the sleep wake schedule but played a significant role on the peripheral metabolic rhythms (78).

Synchronization of these endogenous rhythms is important to optimize body function. The synchronization appears to occur from a variety of endogenous signals such as melatonin, other hormones, and signals from the autonomic system. Other behavioral clues such as food intake and the inherent rise of blood sugars may spur factors such as insulin to also synchronize specific pathways. In one syndrome, isolated delay in an endogenous rhythm has been implicated in individuals with nocturnal eating syndrome, which appears to be a delay in the feeding rhythm. Although appearing benign in this disorder, the timing of food intake can impact insulin sensitivity and metabolism (29). Food intake during the night shift appears to increase insulin resistance and diabetes (65). Similarly chronic circadian disruption appears to change the ghrelin/leptin ratio and lead-in subjective hunger and increased energy intake (42). One hypothesis of the metabolic dysregulation in shift work is a similar desynchronization of the behavioral and endogenous clock, such that the organ systems are not at peak functioning for the required task. Skene and colleagues showed that although many circadian clock markers may demonstrate a stable rhythmicity, most metabolites with nocturnal eating either reversed or lost their rhythm (62). Similar work looking at proteomics shows that simulation of shift work with nighttime eating altered the average abundance and cycling of proteins of nearly 10% of proteins analyzed (19). Similarly, elimination of waste products may also be influenced by circadian disruption. Shift workers appear to have altered brain metabolic waste clearance, specifically with Aβ levels reaching the serum and subsequent gray matter density (81). These altered proteins were involved in immune function, glucose homeostasis, energy metabolism, and elimination of waste products.

Shift workers rely on their overall sleep deprivation to drive their sleep during the day, in contrast to the circadian process, which remains to promote alertness during the day. This results in conflicting drives for sleep and alertness. The circadian rhythms other than sleep-wake mostly remain synchronized with the “natural” light-dark cycle, even after years of permanent night shift work, and do not yield easily to the shifted sleep-wake cycle; this fact is fundamental in understanding the health effects of shift work. A meta-analysis of melatonin metabolite rhythms in permanent night workers indicates that only a small percentage shows complete circadian adaptation. Further evidence suggests that the circadian pacemaker does not adapt to the night shift schedule; the output is also reduced, thus, contributing to less-than-optimal functioning of the body’s rhythms and the downstream health effects of shift work. This “anchoring” of the circadian pacemaker to a typical day-night phase may be due to several factors, including that most night-shift workers revert to a night sleeping schedule on nights off work, potential inertia of the clock to change, and exposure to environmental light in the morning when commuting home or before going to sleep. At the same time, shift workers are performing activities such as eating, which signals opposing messages to the peripheral clocks. This results in further lack of all the organ systems being synchronized.

Although night-shift workers report sleeping better and longer at night than in the daytime, many night-shift workers have difficulty initiating and maintaining sleep even when retiring to bed at normal times. This is probably due to partial shifting of the evening “sleep-forbidden" zone of the intrinsic sleep-wake rhythm into the late evening-early morning hours during the preceding period of night work.

The circadian rhythm can only be shifted in small increments. Ability to make these shifts can be influenced by several predisposing factors such as age, underlying circadian type (night owl, morning lark), and underlying medical health. Factors of the work schedule also influence the ability to adapt, including the speed of the rotation, direction of rotation (delaying sequentially is preferred, eg, days, evenings, nights), length of the shift, and sleep environment during the day.

Epidemiology

Approximately 15% to 30% of the workforce participates in night or rotating shifts (02). The actual prevalence of shift work sleep disorder is unknown but is estimated at 2% to 5% of the general population and 10% to 38% of the population working shifts. One study suggests as high as 63% of workers on rapidly rotating shifts have shift work disorder (70). Similarly, Yong found that 62% of night shift workers have short sleep duration, 30% have poor sleep quality, and 36% have impairment of their activities of daily living (82). This type of circadian disruption can frequently cause the feeling of cognitive impairment. Cognitive issues did not appear to be different between male and female (80). In addition, patients who are morning larks are more likely to have difficulty working night shifts. Many shift workers leave their jobs within the first few years due to poor health.

Prevention

Shift work is an individual and work entity challenge. Many organizations are not familiar with the principles of circadian rhythms and, thus, they may not be aware of the impact various work schedules have on their employees. Growing evidence indicates that institutions that employ shift or rotating shift schedules can have a significant impact on their employees’ health and productivity. Institutions can employ several techniques to promote better sleep and wake among their night and rotating shift workers by focusing on training their managers on factors at the organizational level and training their workers on an individual level. This type of 2-level training was instituted with health care workers and shown to have a significant reduction in sleepiness and other symptoms (20). Appropriate evaluation for work fitness for shift work and the presence of shift work disorder can help reduce the health burden on the workforce by identifying individuals early (30). Institutions can be proactive in their selection of candidates for night or rotating shifts.

Night shift work schedules are usually selected because of the availability of the job, the higher wage, or the reduced amount of supervision. Occasionally, the employer may use criteria to select workers for shift work. Although ability to adapt to shift work is highly variable, one study showed that aligning the schedule to individual shift worker’s chronotype can improve the worker’s sleep. Vetter and colleagues showed that abolishing morning shifts for late chronotypes and night shifts for early chronotypes resulted in a significant increase in self-reported sleep duration during the work week along with improved subjective in sleep quality and wellbeing (74). This study demonstrates the opportunity of matching chronotype to work schedules for shift workers. Similarly, predicting adaptability to a shifting work schedule may help identify individuals who should not be exposed to the potential morbidity of shift work (54). Most potential predictors are controversial or not completely defined. Adaptability to phase changes may also be influenced by genetic predisposition and ethnicity; however, further work is needed to understand the implications of these findings (45). Chen and colleagues showed that features of morningness, preexisting insomnia, or hypersomnia are risk factors for the development of shift work disorder (13). Similarly, Booker and colleagues showed that individuals with poor sleep hygiene were more likely to develop shift work disorder once placed on night shift (08). In brief, factors that may predict intolerance to shift work include being over 40 years of age, having preexisting sleep problems, poor sleep hygiene, cardiovascular or gastrointestinal disorders, needing a rigid sleep schedule in order to sleep well, inability to resist drowsiness, being a morning type, and having a history of family instability.

Institutional measures such as implementing predictable schedules, forward rotation of shifts, rest periods of greater than 11 hours between shifts, and work free periods appear to impact the employees (20). The workplace environment and employer interventions to improve sleep and overall health may have significant benefit for the worker and business (50). The employer and workplace interventions may prevent or diminish the effect of shift work sleep disorder by designing shift length, shift hours, shift-rotation speed, and direction, as long as chronobiological principles are taken into consideration. Rotating shifts should be ordered so the workers progress through days, evenings, then night shift, as opposed to nights, evenings, then days. Clockwise rotation is shown to increase the average amount of workers sleep and reduce attention disturbances and worker stress (60). In addition, the employer can improve the environment by making sure the work area is brightly illuminated to promote circadian adjustment. Procedures for light attenuation can also be implemented at the end of a shift to help with circadian adaptation.

Similarly, workers who choose to work this schedule can reduce the risk of developing symptoms by balancing the need for sleep and circadian principles to their benefit. Meticulous attention to sleep hygiene, minimizing light exposure in the morning, and adopting a consistent sleep schedule 7 days a week may all contribute to prevention of detrimental effects on health. Workers may increase their light exposure in the evening and wear sunglasses on their drive home from work to optimize the effect of light on their circadian system. In addition, workers may utilize melatonin in the morning and practice overall good health habits including appropriate diet and exercise routines to limit secondary health risks. Individuals on rotating shifts can sleep in the morning before a night shift and then take a nap in the afternoon before the shift. During the night shift, workers who are allowed to take short naps (less than 20 to 30 minutes) should limit their caffeine to the first half of the shift and before napping. Caffeine and nicotine should be avoided in the last few hours of the shift. After the shift, sleeping through the morning if possible and then getting sunshine later in the day may help reduce the feelings of disruption.

Differential diagnosis

The two major complaints related to shift work are excessive daytime sleepiness and insomnia. Both of these complaints have well-established differential diagnoses. Other diagnoses to consider in a shift worker with sleep complaints include disorders of sleep initiation and maintenance, inadequate sleep hygiene, delayed sleep-wake phase disorder, insufficient sleep syndrome, as well as other types of insomnia, hypersomnia, and circadian rhythm sleep disorders. For example, patients suffering from insomnia or delayed sleep phase disorder may adopt shift work. Excessive sleepiness should be differentiated from that caused by sleep apnea or narcolepsy, as patients on shift work may have other sleep disorders such as sleep apnea (82). The correlation of sleep complaints with particular work shifts and with changes in shift schedule may help to distinguish shift work sleep disorder from other sleep disorders, but shift work complaints may last over 3 months after the change in the shift. Depression or other psychiatric disturbances, social stressors, or job dissatisfaction are commonly associated with shift work sleep disorder but may also be a new and separate issue. Similarly, workers on night shift or rotating shift may notice their gastrointestinal system feeling “off” or have more symptoms of gastrointestinal upset (84). Sometimes the temporal relationships of these issues with shift work may give clues to the underlying etiology.

Confusing conditions

Patients with shift work disorder frequently present with complaints of excessive sleepiness or insomnia. In addressing these complaints, the clinician should consider common causes of sleep disruption such as sleep apnea as well as other factors such as maladaptive behaviors common in chronic insomnia. The key element in discerning the diagnosis of shift work disorder is the development of the symptoms while on night or rotating shifts.

Diagnostic workup

Most shift workers may only see their physician as part of their routine check-ups or as another medical issue presents. Shift workers seldom consult a physician regarding their sleep problems; therefore, the opportunity for the clinician to intervene occurs during the investigation of these other medical issues. Some workers may present due to sleepiness on the job or accidents due to falling asleep at the wheel may prompt a sleep specialist’s consultation, and inquiry is essential concerning whether or not a sleepy patient works any night shifts. Others may present with reflux or gastrointestinal symptoms (84). Patients with hypertension, metabolic syndrome, vascular issues, and some types of cancer should be asked about shift work and counseled on the need to align their circadian rhythm with good sleep. This may include consideration for changing the shift they work.

The initial evaluation should include a patient history combined with a sleep-wake log or actigraphy for at least 14 days to demonstrate a disturbed sleep-wake pattern for both work and work-free days (64). Usually these provide sufficient information to make the diagnosis of shift work sleep disorder. Symptoms should also be present for a minimum of 3 months. The Epworth Sleepiness Scale may prove useful in the estimate of subjective assessment of sleepiness over the few weeks prior to the clinic visit and has been shown to be reliable on repeated measures. If sleep apnea is a possible contributor, polysomnography is indicated but should be performed at the patient’s natural sleep time. Narcolepsy may also be a consideration and is diagnosed based on findings on an overnight polysomnogram and a multiple sleep latency test, yet the timing of these tests is crucial for an accurate diagnosis. These tests should be performed under the guidance of a sleep specialist, and the patient should be on a normal day-night schedule for at least 2 weeks prior to testing.

In follow up, patients should be assessed for their degree of perceived sleepiness (Epworth Sleepiness Scale), their sleep wake schedule (sleep diaries), and the accompanying symptoms. The provider may assess improvement in the associated symptoms as a marker for adjustment to the schedule. Patients may not improve. Therefore, a break from the night shift work may also provide diagnostic evidence of intolerance of the nighttime work schedule.

Management

Many of the symptoms of shift work sleep disorder are best managed by prevention. Shift workers should be treated in three phases. The first phase is education about the circadian rhythm and use of the time clues (zeitgebers) to maximize the ability to sleep. Patients should be instructed on creating a sleep-inducing environment for the daytime, the timing and use of light and melatonin, and the benefits of minimizing the shift in sleep schedule.

Light is the most important zeitgeber to the circadian oscillator. Bright light exposure has phase-shifting effects with phase advance or delay following early morning or late evening exposure, respectively. Several hours of medium- to high-intensity bright light in the evening, use of dark sunglasses (welders’ goggles or blue light blocking glasses) in the morning before sleep, and sleeping in a totally dark bedroom may all independently promote circadian adaptation to the night shift. Bright light treatment for delaying (delivered in the evening) or advancing (delivered in the morning) circadian rhythms has become standard in preparing astronauts for shift work. However, these are highly selected individuals living in optimal physical conditions for phase-shifting that can be planned for maximal success. Circadian shifts in regular shift workers are much more difficult to achieve due to conflicting zeitgebers and social limitations. High intensity bright light and briefer duration of bright light exposure during the first half of an evening/night shift coupled with a daytime darkness procedure was found to be successful in improving insomnia, anxiety, and depression severity in rotating shift work female nurses (63). A combination of delaying the circadian cycle with dynamic light schedules using more blue light in the 8 hours of wake during the night shift and using blue depleted light for 30 minutes prior to bedtime appears to aid in adaptation to overnight shift work (48). Evening bright light prior to a night shift also appears to reduce fatigue and the rate of errors (18). Although many questions still linger as to how best apply the light therapy, the review and practice parameters of the American Academy of Sleep Medicine suggest it is indicated (guideline level) in the treatment of shift work sleep disorder to decrease sleepiness at work, and light restriction should be used to improve sleep during the day (43; 53). Similarly, the European Network Workplace Health Promotion program developed individual and organizational strategies to prevent the occurrence of shift work disorder (20).

Similar to light, melatonin, the hormone released in response to darkness, can also help shift the circadian rhythm. Phase-response curves for melatonin and light are at nearly a 180-degree phase-angle difference from each other. Melatonin maintains the ability to phase-shift its own endogenous circadian rhythm, core body temperature, and alertness-sleepiness rhythms and has acute sleep-inducing properties. Melatonin may also be used to improve daytime sleep and night alertness in night-shift workers. Overall, a morning dose of melatonin is indicated (guideline level) in the management of shift work sleep disorder to improve daytime sleep (43; 53). For individuals shifting back to a night sleep period, repeated evening melatonin dose of 3 to 5 mg was shown to assist readaptation to night sleep after a simulated night shift, even in the presence of conflicting bright light treatment; it was shown to improve sleep, mood, and memory. Thus, individuals rotating back to day shifts after a period of night shifts may be assisted in entraining to a normal schedule by using melatonin in the evening for a few days. Overall, similar to light, issues of optimal timing and dose need further evaluation. This hormone in the United States is available as a nonprescription supplement, raising questions as to the standardization and purity of various preparations. The United States FDA approved ramelteon and tasimelteon, both selective melatonin agonists with a high affinity to melatonin MT1 and MT2 receptors. Ramelteon was approved for insomnia, and in preliminary studies showed the ability to shift circadian phase (03). Tasimelteon was approved for non-24-hour sleep-wake disorder to help entrain the circadian rhythm (21). This compound was also found to effectively shift a circadian phase and improve sleep in simulated jet lag (47). Light and melatonin work on the SCN through different mechanisms; it may be possible to use combined light-melatonin treatment, with proper timing of each, in order to increase the success rate of the treatment of circadian rhythm disorders (43; 53).

In addition to light and melatonin exposure, shift workers should also be reminded to phase shift their mealtime so that they are eating at regular times and are not having their largest meal just before sleep. Similarly, shift workers should avoid exercise or vigorous activity just before their intended sleep period, as these both may decrease the efficiency of sleep.

Patients may also benefit from decreasing the shift in their own schedule between the days off and on work.

An interesting and promising approach is delaying the circadian clock into a “compromise phase position,” such that it will allow individuals working night shifts to anchor their circadian clocks to a position that is more compatible with nighttime work and daytime sleep yet is not incompatible with late nighttime sleep on days off (25). Chronobiological treatments are demanding, their effects are not always predictable, and it may not be possible to administer treatments in many cases due to work and social limitations. For some patients, the best advice may be to get a daytime job, even if it entails a career change. Minimizing the shift to just a few hours between work and off workdays will help reduce the amount of circadian rhythm shift these individuals experience. Some individuals may find that shifting their sleep period 4 to 5 hours (3 AM to 11 AM) earlier on their non-working nights compared to their usual sleep (8 AM to 4 PM) on nights of work may help accommodate both family and work obligations. Alternatively, sleep in the evening prior to the night shift combined with phase-advancing light exposure in the early morning (second part of the night shift) may achieve the same goal.

Cognitive behavioral therapy for insomnia (CBTi) appears to hold some promise for improving sleep in individuals with shift work. CBTi is well-known to improve sleep in patients with insomnia, but only a few studies have looked at this technique in individuals who are working the night shift. This nonpharmacological therapy focuses on sleep hygiene education, relaxation techniques, and control of the bedtime environment to improve the association of sleep with the bedroom. For subjects working shift work, CBTi appears to have a modest effect on improving sleep and reducing fatigue (28; 51).

For some patients, medication may be beneficial. Medications should only be used after thorough evaluation, trial of nonpharmacotherapies, and clear setting of goals and expectations. Caffeine may reduce sleepiness during the night shift (20). Modafinil and its longer-acting R-enantiomer armodafinil, wake-promoting agents previously indicated for treatment of excessive daytime sleepiness associated with narcolepsy, reduce sleepiness associated with shift work (40); both are approved by the United States FDA for this indication and represent guideline-level patient care strategies within the practice parameters of the American Academy of Sleep Medicine (43). Armodafinil given at the beginning of a night shift was found to normalize nocturnal sleepiness.

Workplaces can aid in reducing shift work-related health consequences. Rotating shifts from days to evenings and then nights is better tolerated. Fixed night-shift workers are more positive in their job outlook than those on rotating or nonfixed shifts (01). Additionally, natural night owls and those individuals without other medical issues and less job stress appear to better tolerate night shift (15).

Overall, a combination of therapies may be important to try to help align the circadian rhythm with the time of wakefulness. Although many of our current strategies are limited in effectiveness, more novel therapies may be on the horizon (58).

Special considerations

Pregnancy

Several studies show low but consistently greater risk of menstrual disruption, lower fertility, greater number of spontaneous abortions, premature labor, and low birth weight associated with shift work in women (36; 68). Longer night shifts were also associated with an increased risk of hypertensive disorders of pregnancy, preeclampsia, difficult delivery, and babies that were small for gestational age (68). The risks in pregnancy appear to apply to both early and late pregnancy (66). Some of these risks even appear with evening shift work because women who are working these shifts have an increase in the risk of gestational diabetes (77). Although little is known about the circadian rhythm during pregnancy, some animal models suggest that maternal chronodisruption may have effects on the offspring (73). Of note, melatonin, a hormone released in relationship to darkness, is transferred in breast milk and exhibits a circadian rhythm. Normally melatonin is in breast milk expressed at nighttime and virtually absent in breast milk expressed during the day. However, in nursing mothers who are working shift work, there is less melatonin expressed at night, raising important questions about the effect of circadian disruption on breast milk composition (10).