Shift Work and Sleep: Optimizing Health,

Safety, and Performance CME

Reviewed by: Natalie P. Hartenbaum, MD, MPH, FACOEM and Phyllis C. Zee, MD, PhD
Compiled by: Carole Drexel, PhD, Director of Accreditation and Outcomes Research, and Kathy
Merlo, Senior Medical Writer, Rockpointe Corporation
Authors and Disclosures
CME Released: 02/24/2011; Valid for credit through 02/24/2012
CME Information
Target Audience
This program is intended for occupational health and environmental physicians, primary care
physicians, and allied health professionals (eg, nurses, nurse practitioners, physician assistants,
and pharmacists).
Goal
Shift work poses a serious public health risk: it can impair an individual’s ability to perform
effectively, it may lead to occupational and traffic accidents, it has numerous negative health
effects, and it infringes on an individual’s ability to sleep, eat normally, exercise, and develop
relationships. In addition, research suggests shift workers are at higher risk for a range of
metabolic disorders and diseases (eg, obesity, cardiovascular disease, peptic ulcers,
gastrointestinal problems, failure to control blood sugar levels, and metabolic syndrome).
Despite the negative impact of shift work sleep disorder (SWSD), it is under-recognized and
undertreated in the clinical setting. Accurate diagnosis and timely and appropriate treatment are
essential to relieve and prevent the acute consequences and long-term health sequelae of this
disorder, and to ensure overall public safety.
Authors and Disclosures
The staffs of Rockpointe Corporation and the University of Cincinnati have nothing to
disclose.The contents of some CME/CE activities may contain discussions of non-approved or
off-label uses of some agents mentioned. Please consult the prescribing information for full
disclosure of approved uses.
Natalie P. Hartenbaum, MD, MPH, FACOEM
President and Chief Medical Officer, OccuMedix, Inc., Dresher, PA
Disclosure: Spouse works for Merck
Phyllis C. Zee, MD, PhD
Professor of Neurology, Neurobiology, and Physiology; Director, Sleep Disorders Program,
Northwestern University, Chicago, IL
Disclosure: Advisory Board: Takeda, Sanofi-Aventis, Merck, Zeo, Philips-Respironics; Stock
Options: Zeo.
Carole Drexel, PhD
Director of Accreditation and Outcomes Research, Rockpointe Corporation, Columbia, MD
Disclosure: Nothing to Disclose
Kathy Merlo
Senior Medical Writer, Rockpointe Corporation, Columbia, MD
Disclosure: Nothing to Disclose
The staffs of Rockpointe Corporation and the University of Cincinnati have nothing to disclose.
Learning Objectives
This activity was designed to address the following IOM competencies: provide patient-
centered care; employ evidence-based practice. Upon completion of this activity, participants
should be able to:
1. Appreciate the role of circadian processes in normal sleep and wakefulness
2. Recognize the impact of sleep restriction on overall health, occupational performance, and
safety
3. Utilize appropriate diagnostic tools in the evaluation of excessive sleepiness
4. Understand an evidence-based approach in the management of SWSD and symptoms
related to excessive sleepiness
Credits Available
Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™
All other healthcare professionals completing continuing education credit for this activity will be
issued a certificate of participation.

Physicians should only claim credit commensurate with the extent of their participation in the
activity.
Introduction
To meet the demands of globalization and a 24-hour society, the United States has become
increasingly dependent on shift workers over the past few decades.[1] The term shift work applies
to a range of non-standard work schedules, such as permanent night shifts, occasional on-call
overnight duty, rotating schedules, and schedules that require early awakening from nocturnal
sleep. Numerous professions use shift workers, including the healthcare, food service, retail,
transportation, manufacturing, and public safety industries.[2] Shift work is an integral part of
professional life for more than 22 million Americans.[3] Among these individuals, approximately
3.8 million people work the night shift on a regular basis, while another 3.3 million work on a
rotating night shift.[4] The National Sleep Foundation's 2005 Sleep in America poll found that
14% of Americans are shift workers.[5]
Although shift work can increase production and customer service without major increases in
infrastructure, shift work poses the possibility of a major public health and safety risk.[1] Shift
work is associated with a variety of negative health effects, as well as significant cognitive and
social burdens (Figure 1).[6] A 2008 poll from the National Sleep Foundation found that shift
workers were significantly more likely than non-shift workers to sleep less than 6 hours on work
days, work more hours on average each week, and have driven drowsy at least once a month
during the past year.[7]
Figure 1.
Shift workers are often required to function at times that are in opposition to their usual
circadian-controlled sleep/wake times, resulting in a conflict with their natural wake/sleep
patterns. A certain degree of difficulty is experienced by most individuals attempting to work at
unusual times within a 24-hour day.[2] Some individuals are more vulnerable to the sleep loss
associated with working a rotating or night shift.[8]
Sleep/Wake Disturbance in Shift Workers
Shift workers can experience excessive sleepiness, which is thought to result, in part, from a
mismatch between the timing of the internal circadian pacemaker and the timing of sleep and
wakefulness.[9,10] A certain degree of sleep deprivation is also involved. Excessive sleepiness
occurs at the time when the homeostatic sleep drive is high, but the suprachiasmatic nucleus
(SCN)'s wakefulness drive cannot effectively offset this drive. It is important to note that some
individuals do not feel sleepy at this time even though they are experiencing excessive sleepiness
(ie, an enhanced tendency to fall asleep during inappropriate times). In contrast, the circadian
drive for wakefulness is inappropriately high at a time when the night shift worker then tries to
sleep in the morning. The misalignment between the work-rest/wakefulness sleep schedule and
the circadian pacemaker that occurs in these patients can result in clinically significant excessive
sleepiness during the night shift or insomnia when trying to sleep the following day, or both.[9]
Shift workers can experience sleep that is fragmented, short in duration, and not restorative. This
further adds to subsequent excessive sleepiness. In some individuals, there is a correlation
between the degree of misalignment and symptom burden.[9] However, adaptation to shift work
schedules can occur in others, without significant negative effects on sleep and function.[11]
Case 1
Mrs. Walters is a 32-year-old white woman who presents to your office with complaints of
feeling constantly tired and even exhausted at times. Discussion with the patient reveals that she
has a history of gastroesophageal reflux disease (GERD) and has been taking the proton pump
inhibitor (PPI) omeprazole for about 2 years, with a significant decrease in reflux symptoms.
Further discussion reveals that the patient has been feeling irritable and has had some difficulty
concentrating at work. She complains that she feels unmotivated, and has little desire for
activities that she used to enjoy, such as tennis and shopping. Review of systems is
noncontributory. When asked if she has problems sleeping, she states that she sometimes wakes
up in the middle of the night and has difficulty falling back to sleep.
Physical examination reveals the following: height, 66 inches; weight, 138 lb; body mass index,
22.3; blood pressure, 144/82 mm Hg; and pulse, 70 beats per minute. Laboratory values are:
hemoglobin, 13.2 g/dL; hematocrit, 40%; platelets, 320,000/mL; white blood cell count, 6,800;
sodium, 138 mmol/L; potassium, 4.0 mg/dL; magnesium, 1.8 mmol/L; thyroid stimulating
hormone, 1.7 mU/mL; fasting glucose, 117 mg/dL; high-density lipoprotein (HDL) cholesterol,
40 mg/dL; low-density lipoprotein (LDL) cholesterol, 152 mg/dL; and triglycerides, 167 mg/dL.
During the mental status examination, you note that the patient has a flat affect. She answers each
question in a soft spoken manner with mild slowing in speech and minimal direct eye contact.
Her responses correspond to the question asked, but with minimal details. She appears to be tired.
The patient denies feeling depressed and states that she just feels run down. She is dressed in
ripped jeans and a T-shirt, her hair is pulled into a ponytail, and she is not wearing make-up.
Top of Form
http://w w w .meds /view article/7374 19926 true

Questions answered incorrectly will be highlighted.

3 INTERNAL 114325

Which of the following disorders would most likely explain the patient's symptoms?
RADIOBUTTON 0

Hypothyroidism
Obstructive sleep apnea syndrome
Major depressive disorder
GERD

• Based on the patient's symptoms and the results of the mental status examination, she was
diagnosed with major depressive disorder.
Discussion
Diagnostic evaluation revealed that the patient has been feeling tired for several years. She
attributed her symptoms to being busy at work and with her family. But she became concerned
when her feelings of tiredness increased noticeably over the past 6 months for no apparent
reason. There have been no significant changes in her life to explain this. She is also distressed
because she has no energy to spend quality time with her family when she is not at work.
The physical examination is essentially normal, except for a slight elevation in blood pressure.
The patient's laboratory values fall within the normal range, except for a slight elevation in the
patient's LDL and triglyceride levels, along with impaired fasting glucose.
The patient was diagnosed with major depressive disorder based on her symptoms of anhedonia,
tiredness, difficulty concentrating, and irritability, along with the results of the mental status
examination. Looking at the other possible causes of the patient's tiredness, she does not report
any of the common symptoms of sleep apnea (eg, loud snoring, reports of breathing pauses
during sleep, abrupt awakening with gasping, and waking up with dry mouth or a sore throat).[12]
Insomnia is also commonly associated with sleep apnea, and an association between insomnia
and GERD has been observed.[13] However, the patient denies having difficulty with insomnia,
and she has been taking omeprazole as prescribed, which has resulted in relief of any symptoms
associated with GERD. Results of the laboratory testing show that the patient's thyroid
stimulating hormone level is normal. Therefore, sleep apnea, GERD, and hypothyroidism are not
likely causes of the patient's tiredness.
Top of Form
http://w w w .meds /view article/7374 19926 true

Questions answered incorrectly will be highlighted.

4 INTERNAL 114326

Which of the following treatments is most appropriate for the treatment of major depressive
disorder in this patient?
RADIOBUTTON 0

Extended-release bupropion
Quetiapine
Zolpidem
Levothyroxine
Dexmethylphenidate

• Extended-release bupropion is an antidepressant agent indicated for the treatment of

major depressive disorder. It belongs to the aminoketone class and is chemically unrelated
to other known antidepressant agents.[14]
Discussion
The patient was started on extended-release bupropion 150 mg/day for the treatment of major
depressive disorder. After 1 week, the dose was increased to 300 mg/day. The extended-release
dose of bupropion was prescribed since better medication compliance has been observed with the
use of medications taken once a day versus more than once a day.
Quetiapine is a psychotropic agent that has been approved for the treatment of schizophrenia and
bipolar disorder.[15] Zolpidem, a non-benzodiazepine hypnotic, is indicated for the short-term
treatment of insomnia characterized by difficulties with sleep initiation.[16] Levothyroxine is a
thyroid hormone that is used in the management of hypothyroidism.[17] The central nervous
system (CNS) stimulant dexmethylphenidate is indicated for the treatment of attention deficit
hyperactivity disorder in patients 6 to 17 years of age.[18] None of these agents are appropriate
management options in this patient.
Case 1 Continued
The patient returns 6 weeks later for a follow-up appointment and tells you that her symptoms
have improved slightly. However, she still feels run down and is having difficulty concentrating
at work. She reports that she has also been late for work several times over the past 3 weeks
because she has overslept. The patient is concerned that she is still feeling so tired.
Top of Form
 http://w w w .meds /view article/7374 19926 true

Questions answered incorrectly will be highlighted.

5 INTERNAL 114328

What additional information can help you determine the most appropriate next steps for this
patient?
RADIOBUTTON 0

The patient's compliance with extended-release bupropion

Amount and timing of caffeine consumption
Sleep/wake patterns and work schedule
All of the above
Bottom of Form
Bottom of Form
Bottom of Form

• All of this information can help to determine the appropriate next steps for this patient. It
is important to know whether or not the patient is taking the antidepressant medication as
prescribed and if there are other factors that may be contributing to her feeling tired.
Discussion
Compliance is an issue with many medications, so it is important to ask the patient whether or not
she is taking the medication as prescribed and if she increased the dose of extended-release
bupropion after the first week. Medication noncompliance may explain why the patient's
symptoms have not improved.
If the patient is taking the antidepressant medication as prescribed, other factors that may be
causing her feelings of tiredness and exhaustion should be evaluated. Inquiring about the amount
and timing of caffeine consumption is important, since caffeine is a stimulant and can disrupt
sleep. It has been found that consuming caffeine continuously throughout the day or immediately
before bedtime can delay the onset of sleep or decrease the quality of sleep.[12] Asking about the
patient's sleep/wake patterns can also be helpful since irregular bedtimes can contribute to poor
sleep quality and excessive sleepiness. Additionally, it is important to ask patients about their
work schedule to determine if work could be interfering with a patient's sleep (ie, early morning
or night shift workers or working a rotating shift) and contributing to feelings of tiredness or
causing excessive sleepiness.
Case 1 Continued
The patient was asked to keep a sleep diary for 1 week to show her sleep/wake patterns. She
states that she has been taking extended-release bupropion as prescribed. She takes 300 mg/day
and has not missed a dose or experienced any side effects. When asked about her caffeine
consumption, the patient reports that she has a cup of coffee with breakfast and sometimes
another cup when she gets to work. She occasionally has a caffeine-free soda in the early
afternoon, but says that she drinks water or non-caffeinated sports drinks most of the day and
with dinner, and avoids having more caffeine since it intensifies GERD symptoms.
When asked about her sleep patterns, the patient reports that she typically goes to bed around
11:00 pm and gets up at 4:30 am on weekdays. When asked why she does not go to bed earlier,
she notes that she spends time playing with the kids, answering personal E-mail, and surfing the
Internet after dinner, and is taking an evening class once a week. She also needs time to complete
household chores, such as cleaning up from dinner, doing laundry, and picking up toys before
going to bed. She says that she is tired when she gets up and comments that she has slept through
the alarm on several occasions, making her late for work. On the weekends, the patient goes to
bed at the same time and usually gets up around 7:00 am when her son wakes up. She says that
she tries to watch the 11:00 pm news in bed before going to sleep, but often falls asleep right
away.
When asked about her work schedule, the patient reports that she has worked as a surgical nurse
for the past 9 years. She is scheduled to work an 8-hour shift, from 7:00 am to 3:00 pm, Monday
through Friday, but frequently chooses to work overtime, resulting in 10- to 12-hour shifts. The
patient is also on call for emergencies and goes into work earlier than scheduled about once a
week. When this happens, she may work up to a 16-hour day. The patient's sleep diary shows that
she goes to bed late, typically falling asleep right after getting into bed, and gets up very early
(Figure 2). She gets, on average, less than 5 hours of sleep per night.

Figure 2.
The patient has been taking extended-release bupropion as prescribed for 6 weeks, with some
improvement in the symptoms of anhedonia and irritability. However, she continues to
experience difficulties with concentration and feeling constantly tired. Admittedly, her symptoms
may be due to a continued depressive disorder, as nonresponse to antidepressants is not
uncommon in patients with depressive disorders. However, sleep deprivation must also be
playing a role, as her work and sleep schedule reveals that she gets up early for her shift, often
works extended hours, and wakes up to go in to work earlier than scheduled about once a week.
She has been describing her symptoms as tiredness or exhaustion, but she is probably
experiencing excessive sleepiness. Patients with excessive sleepiness have an increased
propensity to fall asleep when sleep is inappropriate or dangerous. Excessive sleepiness can result
in a variety of symptoms, including the sensation of fatigue, irritability, difficulty concentrating,
reduced work performance, and depressed mood.[9,19,20] All of these symptoms have been reported
by the patient. Additionally, she has slept through her alarm on several occasions.
This patient gets up early for her morning shift and goes to bed late, typically getting less than 5
hours of sleep a night on workdays. These factors result in chronic sleep deprivation and a
buildup of sleep debt, leading to excessive daytime sleepiness (EDS). There are various types of
sleep deprivation: (1) acute – over the course of one or two nights; (2) chronic – over the course
of weeks or months; (3) partial – curtailing sleep by an hour or two each night; and (4) total –
completely missing a night of sleep. This patient has partial, chronic sleep deprivation. A study
evaluating the behavioral and physiologic consequences of sleep restriction showed that sleep
deprivation can result in a range of neurobehavioral deficits, including depressed mood, slowed
working memory, lapses of attention, reduced cognitive throughput, and perseveration of thought.
Neurobehavioral deficits accumulate over days of partial sleep loss to levels equal to those found
after one to three nights of total sleep loss. Study results also revealed that after days of chronic
sleep restriction (<7 hours per night), significant daytime cognitive dysfunction accumulates to a
level similar to that found following severe acute total sleep deprivation.[21]
Top of Form
http://w w w .meds /view article/7374 19926 true

Questions answered incorrectly will be highlighted.

6 INTERNAL 114329

Which of the following is the best way to measure EDS in the office setting?
RADIOBUTTON 0

Epworth Sleepiness Scale (ESS)

Stanford Sleepiness Scale (SSS)
Multiple Sleep Latency Test (MSLT)
Sleep log
Cerebral spinal fluid (CSF) hypocretin levels
• The ESS is the most appropriate tool for measuring EDS in an office setting.
Discussion
The ESS is a brief questionnaire used to assess global symptoms of sleepiness by asking patients
about their chances of dozing off in eight daily sedentary situations. A score of 10 points or
higher is indicative of clinically significant excessive sleepiness, while a score of 16 points or
higher indicates a high level of daytime sleepiness.[22] The patient scores a 15 on her ESS,
indicating that she is experiencing a significant level of sleepiness while at work. However, it is
important to note that the ESS is a subjective scale and negative findings do not definitely rule
out the presence of daytime sleepiness. Nevertheless, the ESS may be a useful in-office tool for
physicians because it provides additional information during history gathering.
On the ESS, the patient provides an introspective measure of his/her current level of sleepiness
using a 7-point scale.[23] Some individuals who are highly sleepy (readily falling asleep during
activities of daily living) do not have the sensation of being sleepy. In addition, some non-sleepy
individuals who feel a sense of low energy may state that they feel sleepy. Therefore, the SSS is
regarded as being less accurate in detecting EDS.
The MSLT is the standard tool used to evaluate individuals with possible narcolepsy. This nap
study is used to measure how quickly someone falls asleep in quiet, laboratory situations during
five nap opportunities over the course of the day. Sleepy individuals fall asleep more rapidly on
these tests. Individuals with narcolepsy typically fall asleep in less than 8 minutes during an
MSLT and display rapid eye movement (REM) sleep during at least two of these nap
opportunities, a highly abnormal finding. The MSLT is taken immediately following an overnight
sleep study and typically lasts for several hours. Specific data (eg, electroencephalogram,
electroculogram, and electromyogram) are monitored and recorded during the test.[24,25] Although
the MSLT is considered to be a more definitive test of sleepiness, it does take place in a
laboratory and, therefore, is not practical for use in an office setting.
A sleep log or diary does not assess sleepiness but provides information regarding an individual's
sleep/wake pattern, such as bedtime, time spent in bed, sleep interruptions, estimated total sleep
time, and quality of sleep.[9] This information is recorded by the patient for at least 7 days, as
recommended by the American Academy of Sleep Medicine (AASM) guidelines, and, therefore,
cannot be used for immediate in-office assessment of the patient.[2] Nevertheless, the sleep log is
a very important tool for quantifying sleep/wake habits.
CSF hypocretin measurements, which are not routinely performed in most clinical settings, are
typically used to identify narcolepsy, and are not useful for assessing EDS. Low levels of
hypocretin have been found in the spinal fluid of individuals with narcolepsy, and most cases of
narcolepsy are associated with a deficiency in the hypocretin system. Hypocretin is a
neurochemical that helps regulate wakefulness and REM sleep. The exact cause of the loss of
hypocretin-producing cells in the brain is unknown, but autoimmune reaction is suspected as the
cause.[26,27]
Top of Form
http://w w w .meds /view article/7374 19926 true

Questions answered incorrectly will be highlighted.

7 INTERNAL 114330

Which of the following management options is most appropriate for this patient?
RADIOBUTTON 0

Extend the patient's sleep time (eg, go to bed earlier)

Judiciously timed naps
Practice the appropriate sleep hygiene measures
All of the above

Which of the following management options is most appropriate for this patient?
Your Colleagues Responded:
Extend the patient's sleep time (eg, go to bed earlier) 9%
Judiciously timed naps 1%
Practice the appropriate sleep hygiene measures 4%
All of the above 86%
• Of course, the best treatment for sleep deprivation is increased sleep. These management
options can help to increase the amount of sleep the patient gets each night.
Discussion
This patient is sleep deprived and the first step to management must involve increasing her
quantity of sleep. Extending her sleep times by having her go to bed earlier each night on a
regular basis can increase the quantity of sleep and reduce the homeostatic sleep debt. The patient
should ensure that she is in bed for 8 hours each night. On days when she is called into work
earlier than expected, the patient should consider going to bed even earlier to reduce the sleep
deficit. It is also important for the patient to practice the appropriate sleep hygiene measures
(Figure 3),[28] as this can help to ensure that she gets the necessary amount of sleep each night.

Figure 3.
The importance of sleep hygiene measures should be stressed for all shift workers. Specifically,
this patient should be counseled not to watch television in the bedroom, since darkness and quiet
in the bedroom can promote sleep. Discussion regarding planning evening activities earlier, or
doing some of the household chores during the weekend, may also be warranted and beneficial.
The patient should be provided with shift work counseling to ensure that she receives 8 hours of
sleep each night.
Judiciously timed naps can increase the amount of sleep the patient is getting each day. A 20-
minute nap prior to driving home may be beneficial on days she is feeling especially tired.
Additionally, the patient may want to speak with her employer about taking a brief nap during
work hours if she is feeling particularly tired and having difficulty concentrating. The AASM
guidelines state that although the evidence for planned napping before and/or during work to
counteract shift work sleepiness is limited, the available data consistently show an increase in
alertness on the job.[9] Napping during the weekend may also be helpful in decreasing the patient's
excessive sleepiness. However, too much napping can be detrimental. According to the National
Sleep Association, too long of a nap (over 20 minutes) can result in sleep inertia, which is defined
as a feeling of grogginess and disorientation that can result from awakening from a deep sleep.
This state typically lasts for a few minutes to up to a half hour and can be detrimental in
individuals who must perform immediately after waking up from a nap. In patients who are sleep
deprived, the impairment and disorientation following a long nap is more severe.[29]
The endogenous circadian rhythm in humans is closely linked to the external light/dark cycle.
Consequently, bright light can re-entrain (reset) the innate sleep/wake cycle,[30,31] as well as
suppress production of melatonin, a sleep-mediating hormone, resulting in a feeling of
wakefulness.[32,33] To enhance sleep at night, the patient should wear sunglasses during the drive
home, if applicable, and minimize exposure to bright light after she gets home from work.
Avoiding bright light prior to going to bed has been shown to enhance daytime sleep in night
shift workers.[34,35]
Case 1 Continued
The patient is asked to keep a sleep diary over the next 2 weeks and practice the recommended
sleep hygiene measures and behavioral changes. She also receives occupational counseling
regarding the need to limit the amount of overtime she works, particularly if she is feeling tired.
The patient is also counseled about "rescheduling" her day so that she is not performing so many
personal activities after work. The importance of getting at least 8 hours of sleep each night is
stressed.
When the patient returns for a follow-up visit, she says that she has experienced improvement in
the amount of sleep she is getting each night. She is now going to bed at 10:00 pm and has
stopped watching television in the bedroom. She wears sunglasses on the way home and keeps
the lights dim before bedtime. She says that she falls asleep almost immediately and is waking up
feeling less tired compared with 2 weeks ago. On days when she goes to work earlier than
expected, the patient takes a 20-minute nap before driving home from work if she is feeling
overly tired. She also naps for 20 minutes twice a day on the weekend. The improvement in sleep
times and the use of sleep hygiene measures and planned napping has resulted in a decrease in
excessive sleepiness and an increase in concentration at work. An ESS reveals a score of 8,
indicating a reduced level of daytime sleepiness.
Case 1 Conclusions
The patient presented in this case is not the typical shift worker. However, there are various shifts
that require early awakening from nocturnal sleep. In this patient, it is likely that her excessive
sleepiness was due to chronic sleep deprivation. The patient's symptoms persisted following
therapy for depression, suggesting the possibility of a comorbid condition. Behavioral changes
were the first line of management in this patient. She began going to bed earlier and practicing
appropriate sleep hygiene measures, along with planned napping. These changes resulted in an
improvement in daytime sleepiness and increased her concentration at work. The patient should
be advised to continue with these behavioral changes and the sleep hygiene measures.
The patient continues to take 300 mg/day of extended-release bupropion, as she may have
comorbid depression. An increased incidence of depression has been reported in patients
experiencing EDS.[36] Optimally, consultation with a psychiatrist or psychotherapist is warranted.
The addition of psychotherapy should be considered, as the combination of psychotherapy and
pharmacology has been shown to be superior to either management option alone in patients with
depression. The patient's level of depression and extended-release bupropion use should be
monitored closely, and if her depression improves, tapering the patient off the antidepressant may
be warranted. Additionally, the patient's blood pressure, LDL, triglyceride, and impaired fasting
glucose levels should be monitored, as these were all slightly elevated at the initial visit. It is
possible that the patient's GERD, elevated lipid profile, elevated hypertension and hyperglycemia
are comorbidities of her excessive sleepiness.
Case 2
Mr. Harris is a 54-year-old man who presents for follow-up after a diagnosis of obstructive sleep
apnea (OSA). Review of his sleep study shows a baseline Apnea Hypopnea Index (AHI) of 38
and a continuous positive airway pressure (CPAP)-related AHI of 2 at a setting of 8 cm H2O. The
patient reports that he has been using CPAP for at least 8 hours a day for the past 3 months,
without major problems. He says that his sleep quality has improved significantly with the use of
CPAP, as a result of fewer awakenings. However, he says that he still has difficulty falling asleep
and typically spends as long as 2 hours lying awake in bed. He is still experiencing excessive
sleepiness at work, especially during his commute home. Discussion with the patient reveals that
he has been disciplined several times for not returning from break at the appropriate time because
he fell asleep in the break room. For the past 12 years, he has worked the night shift (11:00 pm to
7:00 am) at a manufacturing plant.
The patient also has a history of hypertension, high cholesterol, diabetes, and benign prostatic
hyperplasia (BPH). He is taking the following medications: valsartan, 80 mg/day; simvastatin, 40
mg/day; sitagliptin, 100 mg/day; and finasteride, 5 mg/day. The patient states that he takes his
medications as prescribed most of the time. Review of systems is normal.
Physical examination reveals the following: height, 73 inches; weight, 225 lb; body mass index,
29.7; pulse, 79 beats per minute; and blood pressure, 122/82 mm Hg. A decrease in blood
pressure has occurred with CPAP treatment, as the patient's blood pressure was 152/90 mm Hg
approximately 3 months ago. Laboratory values are: hemoglobin, 15.4 g/dL; hematocrit, 48%;
platelets, 280,000/mL; white blood cell count, 6,200; sodium, 141 mmol/L; potassium, 4.4
mg/dL; magnesium, 2.0 mmol/L; fasting glucose, 108 mg/dL; HDL cholesterol, 42 mg/dL; LDL
cholesterol, 92 mg/dL; and triglycerides, 145 mg/dL.
Top of Form
http://w w w .meds /view article/7374 19926 true

Questions answered incorrectly will be highlighted.

8 INTERNAL 114332

Which of the following tools should be used to further evaluate the patient's sleep issues?
RADIOBUTTON 0

Sleep diary
ESS
CPAP smart card data printout
Patterns of caffeine consumption
All of the above

Which of the following tools should be used to further evaluate the patient's sleep issues?
Your Colleagues Responded:
Sleep diary 5%
ESS 2%
CPAP smart card data printout 2%
Patterns of caffeine consumption 1%
 All of the above 90%
• A sleep diary can provide information on the patient's sleep/wake patterns. The ESS can
be used to assess his level of sleepiness while awake. The CPAP smart card data printout
will show if there are issues reducing the efficacy of CPAP, such as flow-limitation events
or mask leaks. Assessing caffeine consumption patterns is also important since caffeine is
a stimulant and can disrupt sleep.
Discussion
In patients experiencing excessive sleepiness and insomnia for a month or longer, the AASM
recommends the use of a sleep diary for at least 7 days.[2] A sleep log or diary will provide
information about the patient's sleep/wake patterns and quality of sleep.[9] As stated previously,
the ESS is a brief questionnaire used to assess daytime sleepiness (Figure 4).[22] Although this tool
is not validated in night or rotating shift workers and the questions asked may not be completely
appropriate for the measurement of excessive sleepiness in night shift workers, the ESS is a
useful screening tool for evaluating excessive sleepiness in clinical situations.[37] Although this
tool has a good positive predictive value, it is not specific. An overly sleepy patient can
underestimate their level of sleepiness.

Figure 4.
Although Mr. Harris states that he is using CPAP 8 hours per night, data show that patients tend
to overestimate the length of CPAP usage.[38,39] Suboptimal use can contribute to continued
daytime sleepiness. In addition, AHI values may be higher than desirable during CPAP usage due
to mask leaks, poor mask fit, and other factors, which, in turn, can cause continued daytime
sleepiness. The CPAP smart card data printout can provide practitioners with information
regarding how long the patient is asleep and if there are any flow-limitation events (eg, snoring,
apneas, or hypopneas) or mask leaks during sleep.
Caffeine is a stimulant and can disrupt sleep. Therefore, it is important to assess caffeine
consumption in patients who are experiencing insomnia. The effect of caffeine on sleep appears
to be determined by various factors, such as tolerance and/or sensitivity to caffeine, amount of
caffeine consumed, and time between caffeine ingestion and attempted sleep. Caffeine ingestion
immediately before bedtime or throughout the day has been shown to alter the normal stages of
sleep, decrease the reported quality of sleep, delay sleep onset, and reduce total sleep time.[12]
Case 2 Continued
The patient's sleep diary reveals a pattern of night work and daytime sleep on weekdays, and
being awake during the daytime and sleeping at night on the weekends. The sleep diary also
reveals prolonged sleep latencies and multiple awakenings (Figure 5).

Figure 5.
The patient scored an 18 on the ESS, demonstrating a high level of excessive sleepiness on
weekdays. Analysis of the CPAP smart card shows an AHI of 2.2, 90% usage over 4 hours per
night, mean daily use of 6 hours and 15 minutes, and a low mask leak level. The patient states
that he drinks two cups of coffee prior to work in the evening and one cup during work. His last
cup of coffee is consumed 6 hours before going to bed in the morning.
Analysis of the CPAP smart card shows that there are no issues with the machine and that the
patient is using CPAP correctly. Despite positive results with CPAP use, the patient continues to
experience insomnia, as well as excessive sleepiness during work.
Top of Form
http://w w w .meds /view article/7374 19926 true
Questions answered incorrectly will be highlighted.
9 INTERNAL 114334

Which of the following behavioral changes may be helpful for this patient?
RADIOBUTTON 0

Judicious napping before work

Wearing sunglasses during commute home
Use of melatonin before bedtime
Sleep time alterations
All of the above

Which of the following behavioral changes may be helpful for this patient?
Your Colleagues Responded:
Judicious napping before work 3%
Wearing sunglasses during commute home 1%
Use of melatonin before bedtime 4%
Sleep time alterations 5%
All of the above 86%
• Judicious napping before work may help alleviate some of the sleepiness the patient feels.
Wearing sunglasses during the commute home, use of melatonin prior to bedtime, and
sleep time alterations may help increase the patient's quantity and quality of sleep.
Discussion
Behavioral changes are the first step in the management of individuals with excessive sleepiness.
These interventions may help to improve the quantity and quality of sleep, as well as reduce
excessive sleepiness at work. According to the AASM guidelines, data on planned napping
before and/or during work to counteract shift work sleepiness consistently show an increase in
alertness on the job.[9] Study results demonstrate that planned napping (20 minutes to 1 hour)
before or during the night shift increased alertness, improved reaction times and performance,
and resulted in fewer accidents, but did not negatively affect daytime sleep.[40-42]
Bright light can reset the innate sleep/wake cycle and suppress melatonin production, producing
an enhanced feeling of wakefulness.[30-33] Night shift workers who wear dark sunglasses to avoid
exposure to light during the early morning commute home have experienced enhanced sleep once
they get home.[36,37] To improve adaptation to shift work, a multimodal approach using scheduled
bright light and darkness, sunglasses, and melatonin has been recommended.[43]
It appears that melatonin has both direct sleep-promoting and phase-shifting effects, which are
mediated via activity at SCN. The SCN has high-affinity melatonin receptors.[44] Studies have
shown that melatonin administration prior to the daytime sleep period improved the duration and
quality of daytime sleep in night shift workers compared with placebo. Additionally, the use of
melatonin caused a shift in the circadian phase in some individuals, but did not enhance nighttime
alertness. Doses ranged between 0.5 and 10 mg in these studies, and there did not seem to be a
correlation between effectiveness and dosage strength or form.[45-48] According to the AASM
guidelines, there is mixed evidence regarding the benefit of melatonin use before daytime sleep.
In night shift workers, there are good theoretical reasons why melatonin may benefit daytime
sleep, but additional research is also needed.[9] The adverse events associated with melatonin use
include daytime sleepiness, dizziness, stomach cramps, irritability, short-term feelings of
depression, and headache. Individuals should not drive or use machinery for 4 to 5 hours after
taking melatonin.[49]
The sleep diary revealed differences in this patient's sleep/wake patterns on the weekdays versus
the weekends. While there is a pattern of night work and daytime sleep on weekdays, the patient
is awake during the day and sleeps at night on the weekends. These changes in sleep times each
week require the patient's circadian rhythm to continuously adjust, and the body's internal
biological rhythms remain out of sync without a constant sleep/wake schedule during the entire
week. The National Sleep Foundation recommends that shift workers keep the same bedtime and
wake time schedule throughout the week, even on days when they are not working.[1]
In addition to these behavioral changes, all night shift workers should be advised on steps to
improve sleep hygiene and create an environment for restorative sleep. These steps include
ensuring that the bedroom is dark and at a constant comfortable temperature, reducing exposure
to noise before and during the sleep period, and avoiding caffeinated beverages, large meals,
alcohol, and smoking prior to the required sleep period.[28]
Case 2 Continued
The patient returns for a follow-up visit 3 weeks later. He says that he has been sleeping better
and that he now falls asleep within 30 minutes of going to bed, instead of lying awake for 2
hours. He feels that the use of melatonin (3 mg), taken 2 hours before going to bed each morning,
has improved the quality and duration of his sleep. He states that he has been following the
recommended behavioral changes, such as napping for 30 minutes prior to going to work,
wearing dark sunglasses on the drive home, and various sleep hygiene measures, such as making
sure the bedroom is dark, using ear plugs, and not eating a big meal before going to bed. The
patient changed his sleep/wake pattern on the weekends and adjusted the weekday sleep/pattern
so that he is now going to bed and waking up almost at the same time every day of the week, with
a few hours' variation. The patient is also using CPAP when he sleeps.
Although the patient is sleeping much better, he states that he is still experiencing excessive
sleepiness at work. The ESS score is now 16, which is not significantly improved from baseline,
and is still indicative of a high level of daytime sleepiness. He reveals that he has been nodding
off at the wheel during his commute home from work for several months now. He did not report
this issue during his previous visits.
Although behavioral changes are the first step in the management of individuals with excessive
sleepiness, these measures (eg, judicious napping and sleep hygiene measures) have not resulted
in significant improvement in the patient's symptoms. Excessive sleepiness is a hallmark
symptom of shift work sleep disorder (SWSD). The International Classification of Sleep
Disorders (ICSD-2) defines SWSD as the presence of excessive sleepiness and/or insomnia for at
least 1 month in association with the work schedule. The work schedule overlaps the usual time
for sleep (eg, night shift). Additionally, there is evidence of circadian misalignment and disturbed
sleep/wake times, which is usually documented by sleep diary for at least 7 days.[9] Based on the
patient's ongoing symptom of excessive sleepiness, a permanent night shift work schedule, and
the ICSD-2 criteria, he is diagnosed with SWSD.
There are a variety of issues surrounding recognition and diagnosis of SWSD. According to the
AASM, there is no clear boundary between a "normal response" to the rigors of working the
night shift and a diagnosable disorder; therefore, the prevalence of SWSD is not entirely clear. A
literature search conducted by the AASM found that a formal diagnosis of SWSD was rarely used
to describe individuals in shift work research studies.[2] Additionally, there are limited data on the
epidemiology and etiology of SWSD in the scientific literature.[50]
A study by Drake and colleagues reported that the prevalence of SWSD was approximately 10%
in individuals who worked the night shift or a rotating shift, using the criteria of excessive
sleepiness and/or insomnia in individuals who had been working on a night or rotating shift for 2
weeks.[51] According to these findings, an estimated 1% of the working population would meet
the criteria for SWSD,[51] given that approximately 6% of the American workforce are night shift
or rotating shift workers.[52] The International Classification of Sleep Disorders (ICSD-2) coding
manual estimates the prevalence to be 2% to 5%. It is important to note that not all shift workers
develop SWSD.[9]
As behavioral changes did not result in significant improvement in the patient's symptoms, the
use of a wakefulness-promoting agent prior to going to work is discussed with the patient.
Top of Form
http://w w w .meds /view article/7374 19926 true

Questions answered incorrectly will be highlighted.

10 INTERNAL 114337

Which of the following agents is approved by the Food and Drug Administration (FDA) to
improve wakefulness in patients with excessive sleepiness associated with SWSD?
RADIOBUTTON 0

Armodafinil
Duloxetine
Methylphenidate
Clonazepam
Eszopiclone

• Armodafinil, a wakefulness-promoting agent, is indicated to improve wakefulness in

patients with excessive sleepiness associated with obstructive sleep apnea/hypopnea
syndrome, SWSD, and narcolepsy.[53]
Discussion
The patient is started on the wakefulness-promoting agent armodafinil at a dose of 150 mg/day,
taken approximately 1 hour before he starts his shift each night. A randomized controlled study
evaluated armodafinil use in night shift workers with excessive sleepiness associated with
moderate-to-severe, chronic (≥3 months) SWSD. Participants received 150 mg of armodafinil or
placebo 30 to 60 minutes before each night shift. Armodafinil increased mean sleep latency from
2.3 minutes at baseline to 5.3 minutes at the final visit. Patients' diaries showed that treatment
with armodafinil was associated with reduced reported sleepiness as measured with the
Karolinska Sleepiness Scale (KSS) during night shifts versus placebo (-2 vs -1.1 points,
respectively) and the commute home (-1.2 vs -0.6, respectively). Improvement in performance on
standardized memory and attention tests was also noted. Daytime sleep was not disturbed.[54]
Modafinil is a wakefulness-promoting agent approved prior to armodafinil for the management of
patients with SWSD.[55] Results of a study by Czeisler and coworkers showed that treatment with
200 mg of modafinil resulted in a reduction of 2.6 in lapse frequency in patients receiving
modafinil versus an increase of 3.8 in placebo-treated patients during the Psychomotor Vigilance
Test. Improvement from baseline in mean nighttime (work shift) sleep latency (using MSLT) in
patients receiving modafinil compared with placebo was also noted (1.7±0.4 versus 0.3±0.3
minutes, respectively). More patients had improvement in their clinical symptoms (74% vs 36%,
respectively). The study also evaluated the implications of the small improvement in performance
on traffic accidents during the commute home. Fewer modafinil-treated patients (29%) reported
accidents or near accidents compared with placebo (54%).[57] For this patient, armodafinil was
chosen due to its longer duration of action compared with modafinil.[53,55,56]
The proportion of patients remaining sleepy on objective assessment with the use of a
wakefulness-promoting agent highlights the importance of ensuring that the use of
pharmacotherapy is part of a comprehensive program that includes diagnostic screening for sleep
disorders, education, and behavioral treatment interventions designed to optimize sleep and
wakefulness.
The use of modafinil and armodafinil has not been systematically evaluated in placebo-controlled
trials beyond 12 weeks in clinical trials of SWSD. Additionally, modafinil and armodafinil have
not been systematically evaluated in hypertensive patients; therefore, periodic monitoring of
patients with hypertension may be appropriate. The most commonly observed adverse events
(≥5%) with modafinil use are headache, nausea, dyspepsia, diarrhea, back pain, nervousness,
rhinitis, anxiety, dizziness, and insomnia. The most commonly observed adverse events (≥5%)
with armodafinil use are headache, nausea, dizziness, and insomnia.[53.55]
Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor that is approved for the
treatment of major depressive disorder, generalized anxiety disorder, diabetic peripheral
neuropathic pain, and fibromyalgia.[58] Methylphenidate, a CNS stimulant, is used for the
treatment of attention deficit hyperactivity disorder in children ≥6 years, adolescents, and adults
≤65 years.[59] The benzodiazepine clonazepam is indicated for the treatment of panic disorder and
seizure disorders.[60] Eszopiclone, a nonbenzodiazepine hypnotic agent, is approved for the
treatment of insomnia.[61]
Case 2 Continued
The patient returns 6 weeks after starting armodafinil for a follow-up visit. He reports that he is
feeling less sleepy at work and during the commute home in the mornings. He has not fallen
asleep while on break or nodded off at the wheel during his commute home from work for about
a month. The patient continues to take 3 mg melatonin prior to going to bed in the morning and
uses CPAP while sleeping. He also naps for 30 minutes 2 hours prior to going to work, wears
dark sunglasses on the drive home, and practices various sleep hygiene measures. He states that
he now falls asleep within 20 minutes of going to bed each morning.
Top of Form
http://w w w .meds /view article/7374 19926 true

Questions answered incorrectly will be highlighted.

11 INTERNAL 114341

Mr. Harris was diagnosed with hypertension, high cholesterol, diabetes, and BPH prior to
receiving a diagnosis of SWSD. Which of these conditions is not associated with shift work?
RADIOBUTTON 0

Hypertension
High cholesterol
Diabetes
BPH
None of the above; all of these disorders are associated with shift work
 • Shift work has been associated with a variety of conditions including hypertension, high
cholesterol, and diabetes. However, BPH has not been recognized as a condition
associated with shift work.
Discussion
Conditions associated with shift work include cardiovascular issues, metabolic disturbances and
gastrointestinal problems, issues with reproductive health in women, mood and anxiety disorders,
and cancer (breast, colorectal, and prostate).[6] It has been proposed that chronic circadian
misalignment, which occurs with shift work, is the underlying cause of the cardiovascular and
metabolic issues observed in shift workers, although the relationships between these
comorbidities and SWSD have yet to be clarified.[62]
Circadian control causes variations in heart rate and blood pressure throughout the day, with a
reduction in blood pressure and heart rate during sleep. However, the normal nocturnal decline in
blood pressure is not as robust in night shift workers, and there is decreased heart rate variability.
[63]
Hypertension is also more likely to occur in these individuals.[64] Compared with individuals
who work during the day, shift workers have a 40% increased risk of developing cardiovascular
disease.[65] The causes of cardiovascular problems related to shift work have yet to be fully
clarified, but may be the result of changes in heart rate, hormone secretion, metabolism, and
autonomic and sympathetic cardiac control,[66,67] along with the increased rates of obesity and
smoking in this population.[65,66]
Shift work has also been associated with significant metabolic disturbance, including an
increased prevalence of obesity and hypercholesterolemia,[67] as well as an increased prevalence
of diabetes.[68] Results from one study showed that elevated cholesterol and triglyceride levels
were observed more frequently in night shift workers compared with individuals who worked
during the day (P < .01 and P < .001, respectively).[66] Data from another study demonstrated
reduced glucose tolerance and insulin sensitivity with circadian misalignment. In this study,
circadian misalignment caused postprandial glucose responses in the range characteristic of a
prediabetic state in 3 of 8 participants.[62] Although the mechanisms underlying these
derangements are still being clarified, metabolic disturbances in shift workers may occur in
response to eating at unusual times, since food intake acts as a cue for synchronization of the
circadian clock.[69]
Case 2 Conclusions
The patient in this case represents the typical night shift worker and presented with classic
symptoms of SWSD including insomnia and excessive sleepiness associated with a work
schedule that overlaps the normal time for sleep, and evidence of circadian misalignment, which
was documented using a sleep diary. The patient also has OSA, and the use of CPAP has helped
to improve his sleep quality and lower his blood pressure.
Behavioral changes are the first step in the management of excessive sleepiness, and the use of
specific behavioral changes (eg, planned napping and sleep time alterations), along with
sunshades, melatonin, and sleep hygiene measures, helped to improve the patient's quantity and
quality of sleep. Despite the improvement in sleep quality and quantity, the patient reported
continued excessive sleepiness at work and revealed that he had been nodding off at the wheel
while driving home from work in the morning. The wakefulness-promoting agent armodafinil
was prescribed and resulted in improvement in EDS. Since starting armodafinil, the patient has
not nodded off while driving home from work in the morning. However, it is important to inquire
about incidents of drowsy driving or nodding off while driving at subsequent visits and to take
the appropriate actions, if necessary.
The wakefulness-promoting agents armodafinil and modafinil are both indicated to improve
wakefulness in patients with EDS associated with SWSD. It is important to note that
coadministration of armodafinil and the PPI omeprazole increased systemic exposure to
omeprazole by approximately 40%, since armodafinil moderately inhibits CYP2C19 activity. A
dosage reduction may be necessary for drugs that are substrates for CYP2C19. Additionally,
patients using steroidal contraceptives, including depot or implantable contraceptives, should be
cautioned regarding the potential increased risk of pregnancy with armodafinil use and for 1
month following discontinuation of therapy. Patients should also be advised to notify their
physician if they become pregnant, or intend to become pregnant, while taking armodafinil. Both
of these wakefulness-promoting agents carry a risk of abuse and are Drug Enforcement
Administration Schedule IV drugs.[53,55]
This patient has hypertension, diabetes, and high cholesterol, all of which are associated with
shift work. The circadian misalignment that occurs in shift workers has been proposed to
contribute to the development of the cardiovascular and metabolic issues observed in these
individuals. All of these conditions should be monitored closely and managed appropriately.

References
1. National Sleep Foundation. Shift work and sleep. Available at:
http://www.sleepfoundation.org/article/sleep-topics/shift-work-and-sleep. Accessed
February 4, 2011.
2. Sack RL, Auckley D, Auger RR, et al. Circadian rhythm sleep disorders: part I, basic
principles, shift work and jet lag disorders. An American Academy of Sleep Medicine
review. Sleep. 2007;30:1460-1483.
3. McMenamin TM. A time to work: recent trends in shift work and flexible schedules.
Monthly Labor Review. 2007(Dec):3-15.
4. US Bureau of Labor Statistics. Workers on flexible and shift schedules in May 2004.
Washington, DC: US Department of Labor, Bureau of Labor Statistics; 2005.
5. National Sleep Foundation. Sleep in America poll. Adult sleep habits and styles. March
2005.
6. Culpepper L. The social and economic burden of shift-work disorder. Fam Pract.
2010;59(1 Suppl):S3-S11.
7. National Sleep Foundation. Sleep in America poll. Sleep, performance and the workplace.
March 2008.
8. Van Dongen HPA, Belenkey G. Individual differences in vulnerability to sleep loss in the
work environment. Industrial Health. 2009;47:518-526.
9. American Academy of Sleep Medicine. International Classification of Sleep Disorders:
Diagnostic and Coding Manual. 2nd ed. Westchester, IL: American Academy of Sleep
Medicine; 2005.
10. Committee on Sleep Medicine and Research. Board on Health Science Policy. Institute of
Medicine of the National Academies. Colten HR, Altevogt BM, eds. Sleep Disorders and
Sleep Deprivation: An Unmet Public Health Problem. Washington, DC: The National
Academies Press; 2006.
11. Campbell SS, Dawson D. Aging young sleep: a test of the phase advance hypothesis of
sleep disturbance in the elderly. J Sleep Res. 1992;1:205-210.
12. Griffiths RR, Juliano LM, Chausmer AL. Caffeine pharmacology and clinical effects. In:
Graham AW, Schultz TK, Mayo-Smith MF, et al (eds.) Principles of Addiction Medicine,
Third Edition. Chevy Chase, MD: American Society of Addiction, 2003;193-224.
13. Edd EM, Flores S. Sleepiness or excessive daytime somnolence. Geriatr Nurs.
2009;30:53-60.
14. Wellbutrin XL® (bupropion hydrochloride extended-release tablets) prescribing
information. GlaxoSmithKline, Research Triangle Park, NC. December 2008.
15. Seroquel® (quetiapine fumarate) prescribing information. AstraZeneca Pharmaceuticals
LP, Wilmington, DE. 2010.
16. Ambien® (zolpidem) prescribing information. Sanofi-Aventis US LLC, Bridgewater, NJ.
August 2010.
17. Synthroid® (levothyroxine sodium tablets, USP) prescribing information. Abbott
Laboratories, North Chicago, IL. March 2008.
18. Focalin® (dexmethylphenidate) prescribing information. Novartis Pharmaceuticals
Corporation, East Hanover, NJ. April 2009.
19. Schwartz JR, Roth T. Shift work sleep disorder: burden of illness and approaches to
management. Drugs. 2006;66:2357-2370.
20. Shen J, Botly LC, Chung SA, et al. Fatigue and shift work. J Sleep Res. 2006;15:1-5.
21. Banks S, Dinges DF. Behavioral and physiological consequences of sleep restriction. J
Clin Sleep Med. 2007;3:519-528.
22. Johns MW. A new method for measuring daytime sleepiness: the Epworth Sleepiness
Scale. Sleep. 1991;14:540-545.
23. Akerstedt T, Gillberg M. Subjective and objective sleepiness in the active individual. Int
J Neurosci. 1990;52(1-2):29-37.
24. Kristo DA. MSLT. Available at: http://www.sleepeducation.com/Topic.aspx?id=38.
Accessed February 4, 2011.
25. American Academy of Sleep Medicine. Narcolepsy. Available at:
http://www.aasmnet.org/Resources/FactSheets/Narcolepsy.pdf. Accessed February 4,
2011.
26. Mayo Clinic Staff. Narcolepsy. Causes. Available at:
http://www.mayoclinic.com/health/narcolepsy/DS00345/DSECTION=causes. Accessed
February 4, 2011.
27. Peyron C, Faraco J, Rogers W, et al. A mutation in a case of early onset narcolepsy and a
generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med.
2000;6:991-997.
28. Thorpy MJ. Managing the patient with shift-work disorder. Fam Pract. 2010;59(1
Suppl):S24-S31.
29. National Sleep Association. Napping. Available at:
http://www.sleepfoundation.org/article/sleep-topics/napping. Accessed February 4, 2011.
30. Czeisler CA, Kronauer RE, Allan JS, et al. Bright light induction of strong (type 0)
resetting of the human circadian pacemaker. Science. 1989;244:1328-1333.
31. Oren DA, Terman M. Tweaking the human circadian clock with light. Science.
1998;279:333-334.
32. Arendt J. Melatonin and human rhythms. Chronobiol Int. 2006;23:21-37.
33. Sack R, Lewy A, Hughes RJ, et al. Melatonin as a chronobiotic drug. Drug News
Perspect. 1996;9:325-332.
34. Eastman CI, Stewart KT, Mahoney MP, et al. Dark goggles and bright light improve
circadian rhythm adaptation to night-shift work. Sleep. 1994;17:535-543.
35. Smith MR, Fogg LF, Eastman CI. Practical intervention to promote circadian adaptation
to permanent night shift work: study 4. J Biol Rhythms. 2009;24:161-172.
36. Drake CL, Roehrs T, Richardson G, et al. Shift work sleep disorder: prevalence and
consequences beyond that of symptomatic day workers. Sleep. 2004;27:1453-1462.
37. Schwartz JR. Recognition of shift-work disorder in primary care. J Fam Pract. 2010;59(1
Suppl):S18-S23.
38. Platt AB, Field SH, Asch DA, et al. Neighborhood of residence is associated with daily
adherence to CPAP therapy. Sleep. 2009;32:799-806.
39. Weaver TE, Grunstein RR. Adherence to continuous positive airway pressure therapy: the
challenge to effective treatment. Proc Am Thorac Soc. 2008;5:173-178.
40. Garbarino S, Mascialino B, Penco MA, et al. Professional shift-work drivers who adopt
prophylactic naps can reduce the risk of car accidents during night work. Sleep.
2004;27:1295-1302.
41. Purnell MT, Feyer AM, Herbison GP. The impact of a nap opportunity during the night
shift on the performance and alertness of 12-h shift workers. J Sleep Res. 2002;11:219-
227.
42. Schweitzer PK, Randazzo AC, Stone K, Erman M, Walsh JK. Laboratory and field
studies of naps and caffeine as practical countermeasures for sleep-wake problems
associated with night work. Sleep. 2006;29:39-50.
43. Crowley SJ, Lee C, Tseng CY, et al. Combinations of bright light, scheduled dark,
sunglasses, and melatonin to facilitate circadian entrainment to night shift work. J Biol
Rhythms. 2003;18:513-523.
44. Liu C. Molecular dissection of two distinct actions of melatonin on the suprachiasmatic
circadian clock. Neuron. 1997;19:91-102.
45. Sharkey KM, Eastman CI. Melatonin phase shifts human circadian rhythms in a placebo-
controlled simulated night-work study. Am J Physiol Regul Integr Comp Physiol.
2002;282:R454-R463.
46. Sharkey KM, Fogg LF, Eastman CI. Effects of melatonin administration on daytime sleep
after simulated night shift work. J Sleep Res. 2001;10:181-192.
47. James M, Tremea MO, Jones JS, Krohmer JR. Can melatonin improve adaptation to night
shift? Am J Emerg Med. 1998;16:367-370.
48. Yoon IY, Song BG. Role of morning melatonin administration and attenuation of sunlight
exposure in improving adaptation of night-shift workers. Chronobiol Int. 2002;19:903-
913.
49. Melatonin. Available at: http://www.rxlist.com/script/main/art.asp?
articlekey=96903&page=2#SafetyConcerns. Accessed February 4, 2011.
50. Schwartz JR, Roth T. Shift work sleep disorder: Burden of illness and approaches to
management. Drugs. 2006;66:2357-2370.
51. Drake CL, Roehrs T, Richardson G, et al. Shift work sleep disorder: prevalence and
consequences beyond that of symptomatic day workers. Sleep. 2004;27:1453-1462.
52. Beers T. Flexible schedules and shift work: replacing the '9-to-5' workday? Monthly
Labor Rev. 2000;23:33-40.
53. Nuvagil® (armodafinil) prescribing information. Cephalon Inc., Frazier, PA. October
2010.
54. Czeisler CA, Walsh JK, Wesnes KA, et al. Armodafinil for treatment of excessive
sleepiness associated with shift work disorder: a randomized controlled study. Mayo Clin
Proc. 2009;84:958-972.
55. Provigil® (modafinil) prescribing information. Cephalon Inc., Frazier, PA. October 2010.
56. Darwish M, Kirby M, D'Andrea DM, et al. Pharmacokinetics of armodafinil and
modafinil after single and multiple doses in patients with excessive sleepiness associated
with treated obstructive sleep apnea: A randomized, open-label, crossover study. Clin
Ther. 2010;32:2074-2087.
57. Czeisler CA, Walsh JK, Roth T, et al. Modafinil for excessive sleepiness associated with
shift-work sleep disorder. N Engl J Med. 2005;353:476-486.
58. Cymbalta® (duloxetine hydrochloride) prescribing information. Eli Lilly and Company,
Indianapolis, IN. January 13, 2010.
59. Concerta® (methylphenidate HCl) prescribing information. McNeil Pediatrics, Division of
Ortho-McNeil-Janssen Pharmaceuticals, Inc., Titusville, NJ. January 2010.
60. Klonopin® (clonazepam) prescribing information. Genentech, Inc., South San Francisco,
CA. 2010.
61. Lunesta® (eszopiclone) prescribing information. Sepracor Inc., Marlborough, MA.
December 2004.
62. Buijs RM, Scheer FA, Kreier F, et al. Organization of circadian functions: interaction
with the body. Prog Brain Res. 2006;153:341-360.
63. Su TC, Lin LY, Baker D, et al. Elevated blood pressure, decreased heart rate variability
and incomplete blood pressure recovery after a 12-hour night shift work. J Occup Health.
2008;50:380-386.
64. Birkenhager AM, van den Meiracker AH. Causes and consequences of a non-dipping
blood pressure profile. Neth J Med. 2007;65:127-131.
65. Boggild H, Knutsson A. Shift work, risk factors and cardiovascular disease. Scand J
Work Environ Health. 1999;25:85-99.
66. Biggi N, Consonni D, Galluzzo V, et al. Metabolic syndrome in permanent night workers.
Chronobiol Int. 2008;25:443-454.
67. Furlan R, Barbic F, Piazza S, et al. Modifications of cardiac autonomic profile associated
with a shift work schedule of work. Circulation. 2000;102:1912-1916.
68. Kawachi I, Colditz GA, Stamfer MJ, et al. Prospective study of shift work and risk of
coronary heart disease in women. Circulation. 1996;92:3178-3182.
69. Garbarino S, Beelke M, Costa G, et al. Brain function and effects of shift work:
implications for clinical neuropharmacology. Neuropsychobiology. 2002;45:50-56.