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Managing the patient with shift-work disorder.

Practice recommendations

* Behavioral measures, eg, exercise and improved sleep hygiene, can enhance sleep quality and combat insomnia and excessive sleepiness (ES)in shift workers and individuals with shiftwork disorder (SWD) (SOR: B).

* Napping before a shift followed by consumption of a caffeinated drink and, if appropriate, scheduled naps at work, may improve ES in patients with SWD (SOR: C).

* Use of bright light therapy to partially re-entrain the circadian clock should be explored for all night-shift workers-particularly those with SWD (SOR: B).

* The wakefulness-promoting agents armodafinil and modafinil are FDA approved for the treatment of ES in patients with SWD. Alongside nonpharmacologic interventions, they can be included in a comprehensive management plan for SWD (SOR: A).

* Melatonin or other sleep-promoting agents may help shift workers achieve sleep during required rest periods and when adjusting to night-shift work; studies are needed in patients with SWD to better evaluate the utility of these agents in this population (SOR: C).

The goals of treatment for individuals with shift-work disorder (SWD) are to ensure sustained wakefulness when wakefulness is required and to facilitate restorative sleep when sleep is required. Several nonpharmacologic interventions are available for the treatment of SWD, such as the improvement of sleep hygiene, exercise, and timed exposure to light. Although these treatments are recommended as part of the Practice Parameter Guidelines for the Evaluation and Treatment of Circadian Rhythm Sleep Disorders from the American Academy of Sleep Medicine, (1,2) most have been evaluated in shift workers generally, rather than specifically in those with SWD. However, the current definition of SWD requires further validation, and while the delineation between workers who do not thrive under shift-work conditions and individuals who develop SWD remains indistinct, it is likely that literature specific to SWD will remain sparse. (2)

Regardless, such nonpharmacologic interventions should be introduced for all individuals presenting with SWD. Pharmacotherapy may also be required. Two pharmacologic agents-modafinil and its R-enantiomer armodafinil--have been evaluated specifically in patients with excessive sleepiness (ES) associated with SWD and are approved as wakefulness-promoting agents for this indication by the US Food and Drug Administration (FDA).

This article reviews appropriate management strategies and specific interventions--both nonpharmacologic and pharmacologic--that primary care physicians can offer to individuals diagnosed with SWD.

Addressing comorbid conditions

For the individual presenting with SWD, it is essential to identify and address any comorbid conditions that might contribute to poor sleep hygiene and/or cause ES or fatigue during required periods of wakefulness. Perhaps the most relevant comorbidities are other sleep disorders, such as obstructive sleep apnea (OSA), and mood disorders, such as depression. Referral to a sleep specialist may be necessary for individuals with a suspected or confirmed comorbid sleep disorder (see "Recognition of shiftwork disorder in primary care" on page S18 of this supplement). An algorithm for the management of SWD in the primary care setting, including steps to evaluate comorbid disorders, appears in FIGURE 1.

Nonpharmacologic interventions

A range of nonpharmacologic options have been evaluated to relieve the ES often reported by shift workers. These interventions include steps to improve sleep hygiene, scheduled nap times, exercise, and timed exposure to light. Although not all of these interventions have been specifically evaluated among individuals with SWD, such approaches may prove useful as part of a wider management program alongside pharmacotherapy.

Evaluating the work pattern

Certain shift patterns have been shown to be more detrimental than others in terms of their effects on performance? For example, Folkard and Tucker (3) analyzed data from 7 studies that evaluated the risk for incidents (including accidents and injuries) during successive night shifts. They found that the risk approximately doubled with each shift worked, from ~6% during the second night shift to 17% during the third night shift and 36% during the fourth night shift (FIGURE 2). Additional studies evaluating the effects of >4 consecutive night shifts, which were not included in the analysis by Folkard and Tucker, (3) confirm the risk for decreased cognitive performance and increased severe ES. (4,5) The observed marked increase in the risk for incidents during working hours suggests that working more than 4 consecutive 12-hour night shifts should be avoided. Individuals should also be counseled to avoid work shifts that are longer than 12 hours due to the risk accumulated on an hourly basis. (3) Individuals on a rotating shift schedule should be encouraged to rotate their shifts in a clockwise rather than a counterclockwise manner (morning to evening to night shift as opposed to night to evening to morning shift) (FIGURE 3). It is easier to change the sleep/wake cycle to a clockwise shift rotation, as this follows the natural adaptive pattern of delaying the sleep period. (6,7) However, a change of rotation direction does not eliminate the risks associated with SWD.




Improving sleep hygiene

Insomnia during periods when sleep is required is a key feature of SWD. When persistent, the chronic sleep debt such individuals incur may contribute to long-term health detriments, eg, cardiovascular disease and ongoing ES, during periods when wakefulness is required. (See "The social and economic burden of shift-work disorder" on page S3 of this supplement.)

Advice on steps to improve sleep hygiene is relevant to all shift workers--including those with and those without SWD--and should be among the first steps in managing any individual presenting with sleep disturbances. Individuals should be advised on how to create an appropriate environment for sleep in terms of noise, temperature, and mental preparation for sleep (TABLE 1). They should also be encouraged to ensure a single 7- to 8-hour sleep episode during a 24-hour period, as opposed to, for example, two 4-hour sleep periods. (8,9) There is now good evidence to suggest that sleep fragmentation of this type can adversely affect sleep architecture (ie, the natural stages of sleep), which leads to an accumulated sleep debt. (10) Incurring a sleep debt can exacerbate the negative effects of shift work on cognitive performance and may also aggravate any underlying sleep disorder by adding to the ES experienced during periods of wakefulness.


Exercise has been shown to be helpful in promoting sleep onset and improving the perceived quality of sleep. (11) Exactly how exercise promotes sleep remains unclear, but the beneficial effects of exercise on mood and anxiety may contribute. (11, 12) In addition, exercise has been shown to facilitate phase shifting of the circadian system (13) and thus may help in the adaptation process to shift work. (14) The most appropriate timing and type of exercise to support individuals with SWD remain to be defined, although there is no evidence to suggest that short bouts of exercise during a work period would be beneficial. In one study of 12 volunteers undergoing a period of sleep deprivation, short bouts of exercise increased alertness for a short time, but this benefit was lost in less than an hour. (15)

Further research is needed to fully define the benefits of exercise among individuals with SWD and to define the optimal timing and regimen to facilitate phase adaptation and reduce the symptom burden among this population.

Scheduled naps

Several studies have indicated that scheduled napping for shift workers may be useful in relieving ES during work periods. (16-22) The optimal duration and timing of such naps have yet to be defined, although one study suggested a longer nap during a night shift (120 minutes vs 60 minutes) was better in terms of sustaining cognitive performance in the early hours of the morning and that sleep efficiency was greater when the nap was taken later in the work shift. (18) Even short naps of<l hour appeared to improve alertness among experienced nightshift workers. (21) Finally, napping before a night shift may also be beneficial in improving performance, particularly when combined with subsequent caffeine intake. (22)

No studies to date have evaluated napping in subjects with SWD. Furthermore, introducing such an intervention may not be practical for all individuals with SWD. Appropriate facilities may not be generally available in the workplace, and napping while "on duty" may be considered unprofessional or ethically unacceptable in some work settings. For example, concerns regarding continuity of care for patients may impede the implementation of scheduled napping among health care workers. (16)

Additional studies evaluating the health, safety, and performance benefits of scheduled nap times for shift workers and among those with a diagnosis of SWD will be required if any cultural change to allow napping is to be achieved.

Light exposure

The human endogenous circadian rhythm is closely linked to the external light/dark cycle; this interaction involves the receipt of daylight-stimulated nerve activity via the retinal ganglion and the retinohypothalamic tract and is controlled by the suprachiasmatic nuclei of the hypothalamus (see "The characterization and pathology of circadian rhythm sleep disorders" on page S12 of this supplement). (23) Consequently, bright light can incrementally reset (re-entrain) the innate sleep/wake cycle (24,25) and can promote wakefulness by suppressing the production of the sleep-mediating hormone melatonin. (26,27) The interaction between light exposure and the endogenous circadian rhythm forms the basis for bright light therapy as a countermeasure for sleep disturbance among night-shift workers. (28)

Evidence suggests that light therapy can entrain the circadian pacemaker to suit night-shift work and so can be used to support night-shift workers in adapting to their shift pattern. (29,30) Bright light (~2500 lux vs normal lighting of ~150 lux) during the work period, combined with regular sleep periods in a darkened room between shifts, significantly (P < .05) delayed the dim-light melatonin-onset response in 54 subjects undergoing a simulated night-shift work pattern, indicating a physiologic phase shift. (31) Such partial re-entrainment improved performance, alertness, and mood during the work period among healthy adults. (32)

A separate study, again using a simulated night-shift work pattern, suggested that brief (1-hour) bright light (~3000 lux) exposure combined with caffeine intake during a night shift maintained cognitive performance throughout the work period in 11 subjects, but that brief bright light exposure alone could, in fact, degrade performance. (33) Reducing light exposure on the commute home from work using sunglasses (or goggles) has been shown to assist with achieving sleep when the worker arrives home (34,35) and to support the partial circadian re-entrainment attained with bright light therapy. (34,36)

The optimal bright light exposure to facilitate partial re-entrainment of the circadian rhythm among nightshift workers has yet to be established. The above studies used a variety of regimens, from constant bright light throughout the work period (31) to intermittent delivery of bright light. (32) A recent study has suggested that a combination of afternoon/evening sleep (between 2 PM and 10 PM) and phase-advancing light therapy (between 3 AM and 7 AM) may be optimal for maintaining alertness in individuals undergoing a simulated night-shift (11 PM to 7 AM) work pattern comprising 4 day and 3 night shifts over 10 days. (37) However, none of these studies have been conducted specifically in patients with SWD.

Reducing the effects of ES when commuting

ES is a well-established risk factor for motor vehicle accidents. (38,39) The potential for motor vehicle accidents on the commute home from work is of considerable concern among shift workers, as they are at greater risk for such an event following a night shift. (40-43) Individuals with SWD should be counseled to minimize their risk for a motor vehicle accident during the commute home. Practical steps are summarized in TABLE 2.

Attention to diet

One study has suggested that attention to dietary composition may have an impact on alertness and performance among individuals working night shifts in a hospital setting. (44) The study suggested that a diet with a carbohydrate-to-protein ratio of around 3:1 is optimal in terms of benefits for both mood and psychometric performance.

Pharmacologic interventions

Wakefulness-promoting agents

The wakefulness-promoting agents modafinil and armodafinil (the R-enantiomer of modafinil) are currently the only agents specifically approved by the FDA for the treatment of ES associated with SWD. Approval of modafinil for this indication was based on the results of 2 controlled clinical trials (TABLE 3). (45,46) Modafinil significantly improved wakefulness, as measured using patient-reported diary data and changes on the Multiple Sleep Latency Test (P < .001 and P = .002, respectively) in those who had ES as a consequence of SWD. (45) Attention was also significantly improved in the modafinil group compared with placebo (P < .001), and significantly fewer participants treated with modafinil reported accidents or near misses during the commute home than did those who received placebo (P < .001). (45) Additionally, modafinil significantly improved self-reports of functioning (in terms of productivity and vigilance; P < .05) and quality of life (P < .05) in individuals with SWD. (46)

In these 2 studies, headache was the most commonly reported adverse event, and nausea was the next most prominent adverse effect with modafinil. In the study by Czeisler and colleagues (45) more modafinil-treated patients experienced insomnia compared with the placebo group (6% vs 0%, respectively; P < .01).

Armodafinil has been shown to improve wakefulness in individuals with ES associated with SWD in a controlled clinical trial (TABLE 3). (47,48) This study showed armodafinil to be significantly better than placebo at improving wakefulness, reflected by a significantly prolonged sleep latency throughout the night among nightshift workers with SWD (P < .0001). Compared with placebo, treatment with a single dose of armodafinil 150 mg, 30 to 60 minutes before the start of the shift, significantly reduced ES at work (P < .0001) and during the commute home (P : .0027) and did not adversely affect daytime sleep. (47,48) As observed for modafinil, headache and nausea were the most common treatment-emergent adverse events in patients with SWD who took part in these 2 studies.

To date, no studies have been performed that directly compare the efficacy of armodafinil and modafinil; however, the 2 wakefulness-promoting agents do have different pharmacokinetic profiles. (49,50) Compared with modafinil, armodafinil takes longer to reach its peak plasma concentration and is present at higher concentrations for a longer period after administration, resulting in its wakefulness-promoting effects lasting throughout the day. (49,50) The longer duration of armodafinil's effects and its potential for once-daily dosing make it an appropriate and convenient choice for patients with SWD.


Stimulants, such as methamphetamine, have been shown to enhance wakefulness in individuals undergoing simulated night-shift work. (51,52) However, amphetamines can induce rebound insomnia and this, combined with their adverse cardiovascular effects and their abuse potential, makes them less than ideal options for an often chronic condition such as SWD. (53) Methamphetamine has not been evaluated as an intervention for individuals with a diagnosis of SWD and, although it is effective at improving performance and mood during one or more night shifts after single doses, its usefulness in managing SWD on numerous sequential nights is questionable.

A number of studies among individuals undergoing simulated night-shift work suggest that caffeine may be useful to promote wakefulness during the work period, although there may be some residual effects on daytime sleep depending on the caffeine drink selected. (54-56) One study suggested that low-dose repeated caffeine administration may improve performance at the expense of increasing subjective ES during periods of extended wakefulness. (57) As discussed above, caffeine in combination with other wakefulness-promoting strategies, including scheduled napping and bright light therapy, has proved to be a promising intervention under simulated shift-work conditions. (22,23) However, the appropriate dose and timing of caffeine intake to optimize performance and mood during a night shift have not yet been determined. Higher caffeine doses may induce a state of hyperstimulation and can even be toxic. (58) Moreover, habitual caffeine intake can lead to the development of tolerance to its effects, (59) abrogating the efficacy of caffeine intake in the long-term management of an often chronic condition such as SWD. To date, regular moderate caffeine intake has not been specifically assessed among individuals with SWD.

Other pharmacologic options for SWD

Administration of the sleep-mediating hormone melatonin can promote daytime sleepy However, while some studies have reported that melatonin is helpful for inducing daytime sleep in simulated and real-world shift-work conditions, (61-64) others have failed to demonstrate any objective or subjective benefit. (65) Single doses of melatonin taken before the required sleep period in simulated shift-work studies of healthy subjects have been shown to decrease sleep latency and increase sleep duration. (62) Melatonin may be most beneficial as part of a phase-advancing program to support individuals in adjusting to night-shift work rather than as a chronic therapy for SWD. (61,63,64,66)

Hypnosedatives, or sleep-promoting agents, taken before required sleep periods have also been evaluated in simulated shift-work conditions. Zolpidem, zopiclone, triazolam, and temazepam have all been shown to increase sleep duration during the day and to improve wakefulness during the night shift. (52,67-70) Only zopiclone has been evaluated among shift workers. (70) In a study of 12 healthy male volunteers working 12-hour shifts, a single dose of zopiclone 7.5 mg taken before the required sleep period significantly improved sleep at night, but this improvement did not reach statistical significance when the required sleep period was during the day. No studies of hypnosedatives have been conducted among individuals with SWD. The greater effect of hypnotics on night-time sleep suggests that they are less efficacious at improving disturbed sleep when given out of phase with the usual sleep period.


Although few interventions have been studied specifically among individuals with SWD, there are a range of practical steps that clinicians can offer to relieve its adverse effects and to reduce a patient's risk of experiencing the potentially fatal consequences of this disorder.

Appropriate interventions include steps to improve sleep hygiene, and evaluation and appropriate referral for comorbid conditions, with particular emphasis on comorbid sleep disorders. Strategies to promote adaptation to the required sleep/wake cycle should also be implemented. These can include bright light therapy (before or during a night shift), reduction of exposure to daylight on the commute home from work, and/or medication with melatonin before a required sleep period, or combinations thereof. (32,34,36,66) These strategies have proved useful among shift workers in general, and further investigation of such strategies would be valuable among those with SWD. Steps to improve shift schedules (eg, the use of clockwise-rotating shifts and avoiding shifts longer than 12 hours), and measures to improve shift-work conditions, such as bright light exposure and appropriately timed naps, may also be helpful.

The wakefulness-promoting agents modafinil and armodafinil are the only interventions with FDA approval for use in patients with SWD and have been evaluated specifically among individuals with ES associated with SWD. These agents have been proven to reduce ES during the work period, with associated benefits in terms of a reduced incidence of accidents or near misses during the commute home. Initiation of wakefulness-promoting therapy should be considered early in the management of individuals with SWD.

Future research should focus on the potential of interventions known to promote wakefulness or sleep specifically among individuals with SWD. In the meantime, clinicians caring for individuals with SWD should develop individualized management strategies that incorporate both nonpharmacologic interventions and pharmacologic therapies, such as a wakefulness-promoting agent before the work period with or without a sleep-promoting agent before the required sleep period.


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Michael J. Thorpy, MD

Director of the Sleep-Wake Disorders Center

Montefiore Medical Center

Bronx, New York

Dr Thorpy reports that he serves as a consultant to and on the speakers bureaus of Cephalon, Inc., and Jazz Pharmaceuticals, Inc.
TABLE 1 Steps to achieve an appropriate
environment for restorative sleep

Step                        Practical advice

Ensure the room is          * Ensure the room has
dark if sleep is required     sufficiently well-lined cur-
during daylight               tains, or install black-out
                              blinds on all windows

Ensure a constant           * Aim for a temperature of
temperature in the            around 20[degrees]C (68[degrees]F)
bedroom                     * Avoid too many bedclothes

Reduce noise exposure       * Avoid watching television
before and during the         or listening to loud music
required sleep period         immediately before the
                              required sleep period
                            * Use a room at the rear of the
                              house if near a busy road
                            * Consider ear plugs if the
                              ambient noise is intrusive
                            * Put telephones on an
                              answering machine
                            * Ask family members to be
Avoid large meals,          * Schedule meal times so that
caffeine-containing           the main meal of the day is
drinks, smoking, and          eaten during or before the
alcohol before the            work period
required sleep period       * Consider having a warm,
                              milky drink before the
                              required sleep period

TABLE 2 Reducing the risk for motor vehicle accidents during the
commute home

Steps to recommend                 To be avoided

* Consider using a taxi service    * Avoid traveling at high speeds
  and/or car pooling, preferably     on highways
  with a driver who has not just
  completed a night shift          * Do not rely on rolling down
                                     the window and turning up the
* Consider taking a nap before       radio-these actions will only
  driving home                       relieve sleepiness very briefly

* Try to minimize the commute      * Do not continue to drive when
  time, eg, move closer to the       feeling sleepy; pull over at a
  workplace                          rest stop and take a nap

* Consider using public

* If sleepy while driving, pull
  over at a rest stop and take a

TABLE 3 Improved wakefulness and reduced ES associated with
FDA-approved wakefulness-promoting agents (45-48)

                                                       N (evaluable
Citation      Population         Regimens              population)


Czeisler      Adults (18/60      Modafinil 200 mg           89
  et al (45)  years) with SWD                              104
              working [greater   Placebo
              than or equal
              to] 5 night        Taken 30-60 minutes
              shifts/month       before the start of
              with [greater      the work shift for
              than or equal      12 weeks
              to] 3 worked

Erman et      Adults (18/60      Modafinil 200 mg           87
  al (46)     years) with SWD                               g0
              working [greater   Modafinil 300 mg
              than or equal                                 86
              to] 5 night        Placebo
              with [greater      Taken 30-60 minutes
              than or equal      before the start of
              to] 3 worked       the work  shift for
              consecutively      12 weeks


Drake et      Adult permanent    Armodafinil 150 mg        112
  al, (47)    or rotating                                  104
              night/shift        Placebo
Roth et       workers with SWD
  al (48)     working [greater   Taken 30-60 minutes
              than or equal      before the start of
              to] 5 night        the work shift for
              shifts/month       12 weeks

Citation      Key findings


Czeisler      * Mean sleep latency change from
  et al (45)    baseline [+ or -] SD:
                --Modafinil: 1.7 [+ or -] 0.4 minutes
                --Placebo: 0.3 [+ or -] 0.3 minutes (P = .002)

              * Change from baseline in the median
                frequency of reported attention lapses:
                --Modafinil: Reduced by 2.6
                --Placebo: Increased by 3.8 (P < .001)
              * Reported accidents/near accidents while
                commuting home:
                --Modafinil: 29%
                --Placebo: 54% (P < .001)
Erman et      * Modafinil 300 mg significantly improved
  al (46)       overall patient functioning vs placebo as
                measured using the FOSQ:
                --Increase from baseline in FOSQ score:
                2.3 vs 1.6 points, respectively (P < .05)
              * Modafinil 200 mg and 300 mg both
                significantly improved quality of life vs
                placebo as measured using the SF-36
                mental health component score:
                --Mean change from baseline of 3.2, 3.7,
                and 0.7 points, respectively (P < .05 for
                both doses vs placebo)


Drake et      * Mean sleep latency change from
  al, (47)      baseline:
                -Armodafinil: 3.1 [+ or -] 4.5 minutes
Roth et         --placebo: 0.4 [+ or -] 2.9 minutes (P < .0001)
  al (48)
              * Reported ES levels on the KSS were
                significantly reduced with armodafinil vs
                placebo (P < .005).

              * Change in the maximum level of
                sleepiness (electronic diary data)
                --During the work shift: 2.0 vs 1.1 points,
                respectively (P < .0001)
                --During the commute home: 1.2 vs 0.6
                points, respectively (P = .0027)

ES, excessive sleepiness; FOSQ, Functional Outcomes of Sleep
Questionnaire; KSS, Karolinska Sleepiness Scale; SD, standard
deviation; SF-36, Medical Outcomes Study Short-Form (36-item) Health
Survey; SWD, shift-work disorder.
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Article Details
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Author:Thorpy, Michael J.
Publication:Journal of Family Practice
Geographic Code:1USA
Date:Jan 1, 2010
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