1. No category

PROCEEDINGS
TREATMENT OF INSOMNIA*
—
Nancy Nadolski, FNP, MSN, MEd, RN†
ABSTRACT
Any treatment for insomnia should accomplish
3 goals: induce sleep, maintain sleep, and promote functionality the next day. Insomnia treatments include behavioral, cognitive, or
pharmacotherapy, alone or in combination. In
general, behavioral and/or cognitive therapy
should be part of any first-line approach. Before
any treatment is administered, it is necessary to
determine the type of insomnia (eg, trouble falling
asleep or trouble staying asleep) in addition to
ensuring commitment from the patient to make
sleep a priority and offer commitment from the
healthcare practitioner to be available for the long
term. This article reviews the available behavioral
and cognitive therapies for which there is evidence of their benefit (ie, relaxation training, stimulus control therapy, sleep restriction, sleep
hygiene education, and cognitive therapy). Many
behavioral therapies can be conducted by a primary care practitioner. The article also reviews the
3 treatment strategies for pharmacotherapy (ie,
antihistamines, γ-aminobutyric acid receptor agonists, and melatonin receptor agonists). A brief
discussion of newer drug therapies also is included. The nurse practitioner’s role is vital in establishing the impact of insomnia on mental and
physical health. Assessing sleep at each visit will
create a standard that the patient will identify as
imperative as other vital signs.
(Adv Stud Med. 2006;6(10D):S1033-S1039)
*Based on a presentation at a symposium held at the
2006 National Conference of the American Academy of
Nurse Practitioners, Grapevine, Texas, June 21, 2006.
†Nurse Practitioner, Foothills Foundation, Boise, Idaho.
Address correspondence to: Nancy Nadolski, FNP,
MSN, MEd, RN, Nurse Practitioner, Foothills Foundation,
223 West State Street, Boise, ID 83702.
E-mail: [email protected].
Johns Hopkins Advanced Studies in Medicine
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T
he goal of any treatment for insomnia
is, essentially, to go to sleep, stay asleep,
and feel good the next day. To determine the best treatment for a particular
patient, it is necessary to determine the
type of insomnia (eg, trouble falling asleep or trouble
staying asleep), which is best measured by using a sleep
diary for 2 weeks.
Insomnia treatments include behavioral, cognitive,
or pharmacotherapy, alone or in combination. In general, behavioral and/or cognitive therapy should be part of
any first-line approach, because not every patient wants
or is willing to take medication for insomnia, and pharmacotherapy may be contraindicated for some patients.
Also, as will be discussed, although pharmacotherapy is
especially useful for treating acute insomnia, behavioral
and cognitive therapies not only increase the chances of
treatment success but also are more effective at preventing future insomnia episodes.
BEHAVIORAL THERAPY
Behavioral therapy is designed to tighten the relationship between sleep behavior and bedtime. It is
accomplished through establishing rituals that promote better sleep. The disadvantage with behavioral
therapy is that it can take up to 12 weeks or longer to
affect sleep quality.
For a patient to extract the most benefit, behavioral
therapy requires a commitment by the patient to make
sleep a priority, specifically to take stock of his or her personal sleep needs, face up to his or her sleep problems,
learn to manage sleep crises, take age into account
(because sleep needs differ throughout life), and adopt a
sleep-smart lifestyle.1 The best and most effective way to
improve sleep hygiene is to adopt a regular schedule, in
particular maintaining a regular sleep schedule 7 days per
week. This can even be written as a “prescription” for the
patient. Other more regimented therapies include sleep
restriction, stimulus control, and relaxation training.
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PROCEEDINGS
Sleep restriction ensures that time in bed is equal to
time asleep. This will avoid the anxiety of lying awake in
bed, worrying about sleep, and increasing the association
of sleep as an unpleasant or stressful experience. Sleep
restriction usually starts by asking the patient to identify
how many hours of sleep he or she is getting.
Maintaining a sleep diary may be necessary to accurately determine this. If the patient says, “I’m only sleeping
5 hours a night,” restrict bedtime to only 5 hours (eg,
going to bed at midnight and waking at 5:00 AM). This
initially creates a sleep debt and the patient will be very
tired the first few days, but often it also relieves anxiety
about going to sleep. Also, because patients with insomnia mistakenly spend extra time in bed trying to fall
asleep, sleep restriction ensures that the sleep debt accumulates to such a degree that sleep will more easily follow. The allotment of restricted sleep time (which should
not be less than 5 hours) can then be added to by 15 to
30 minutes per week, until it builds up to a sleep duration that is best for the patient. Although it produces the
most rapid changes in sleep patterns, some patients may
not be motivated to pursue this type of therapy.2
With stimulus control, the patient must examine
not only the environment in which he or she sleeps, but
also the environment that he or she is letting go of when
succumbing to sleep. Depending on the patient, this
may involve removing reminders of insomnia (eg, a
clock), removing any physical stimuli that can prevent
sleep onset or duration (eg, a snoring spouse, a pet, or a
television), using the bed only for sleeping and sexual
relations (ie, no paying bills, working, eating, or watching television in bed), and sleeping only in bed (with no
napping). Stimulus control also tightens the relationship between going to bed and going to sleep by requiring the patient to get up and out of bed if he or she is
unable to fall asleep in 15 to 20 minutes and doing
something until the patient is tired again. This can be
repeated as often as necessary. Finally, the patient should
avoid any activity that may stimulate the mind before
bedtime, such as checking e-mail, watching the news, or
discussing a topic that causes anger or angst.
In the place of these stimuli are relaxation techniques
that help to quiet the mind, relax the body, and create
bedtime rituals, which also help to foster sleep hygiene.
These techniques can include reading, listening to
music, praying or meditating, a hot bath, comfortable
pajamas (or sleeping nude, if that is a patient preference)
and linens, cooler bedroom temperature, and being only
slightly hungry. Because these techniques can sometimes
S1034
induce performance anxiety, the selected technique
should be started during the day, when there is no pressure or expectation of sleep, and practiced regularly.2
The other possible advantage with relaxation techniques is that they can be self-taught, which can lower
healthcare costs. A recent small study by Morin et al3
illustrated the benefit with this type of program. A total
of 192 patients with insomnia were randomized to no
treatment or a self-help program, which consisted of 6
educational booklets mailed weekly. The booklets provided information on insomnia, healthy sleep practices,
behavioral sleep scheduling, and cognitive strategies.
After 6 months of follow-up, the intervention effectively
improved all measured insomnia symptoms. The
improvements were statistically significant, but clinically
modest. The authors note that the study had several limitations, including poor compliance (43%–62%) and a
changing patient population (ie, approximately 50% of
patients had a different sleep status between study selection and randomization). The authors note that “it is
plausible then that additional social support, feedback,
and reinforcement throughout intervention, perhaps
through telephone consultations, could improve both
compliance and outcomes.”3 Nurse practitioners (NP)
are ideally suited for this but, ironically, are not reimbursed by insurance companies for this type of care.
COGNITIVE THERAPY
Sleep behavior is learned. Our attitudes and beliefs
about sleep were instilled in us from our parents.
Therefore, the first step in cognitive therapy for insomnia
is to determine how the patient perceives sleep (eg, Is
sleep a priority? How much sleep do you think you
need?). Many patients misjudge how much sleep is optimal for them, perhaps thinking they only need 6 hours
of sleep when they need more or focusing on getting 8
hours of sleep when they may not need that much. Other
common misconceptions about sleep include myths (eg,
the best sleep is before midnight) or fear of “going crazy”
or becoming psychotic or dying without sleep. In fact, it
has never clearly been shown that lack of sleep causes psychosis. Cognitive therapy involves restructuring (ie, challenging and replacing) anxiety-producing and erroneous
beliefs about sleep and sleep loss. Cognitive therapy is
usually administered by a mental health professional or a
clinician who specializes in sleep disorders.
Cognitive therapy is an important treatment option
because it offers both short- and long-term benefits,
Vol. 6 (10D)
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November 2006
PROCEEDINGS
particularly when combined with behavioral therapy
(Figure 1).4-6 Therefore, it also can prevent future
episodes of insomnia or better prepare the patient in
handling these episodes when they do occur. Cognitive
therapy also can help distinguish cases of true insomnia
from age-related sleep changes and to reduce the emotional distress that insomnia ultimately inflicts.5
is of the same quality and consistency as a normal night’s
sleep—that is, the patient should be able to fall asleep easily, stay asleep, and be functional the next day.
There are many neurotransmitters involved in the
sleep-wake cycle: sleep promoting (ie, adenosine, melatonin, galanin, and γ-aminobutyric acid [GABA]) and
wakefulness-promoting (ie, norepinephrine, orexin,
COGNITIVE-BEHAVIORAL TREATMENT
THE NURSE PRACTITIONER’S ROLE IN CBT
A key component in CBT is for NPs to monitor
patterns of the patient and the bed partner. CBT
requires making sleep a high priority for all sleepers in
the household. Educating the patient about sleep
architecture and what it means for better sleep outcomes is very important. Also, seeing the patient on a
weekly basis while therapy is being employed allows
for feedback and support and the chance for the
patient to develop insight and judgment about barriers
to getting to sleep and staying asleep.
PHARMACOTHERAPY
By the time many patients with insomnia present to a
healthcare practitioner (HCP), they usually are desperate
for a “quick fix,” saying, “Just knock me out. I’m so tired
of being tired.” For patients unwilling to pursue behavioral and/or cognitive therapy, or in whom the insomnia
is not resolved, there are several medication choices.
However, the specific medication must produce sleep that
Johns Hopkins Advanced Studies in Medicine
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Wake after sleep onset, min
Figure 1. Long-term Outcomes with CBT vs
Medication for Insomnia
Improvement
Cognitive and behavioral treatments can be administered separately, but most clinical research has focused on
their combination: cognitive-behavioral therapy (CBT).
CBT is especially useful in addressing perpetuating factors that contribute to insomnia. In chronic insomnia,
the patient inadvertently creates a vicious cycle of
impaired sleep, fatigue, worry about sleep, excessive time
in bed or napping to make up for the sleep debt, and
ultimately creating physical and emotional arousal,
which further inhibits sleep.2 Pharmacotherapy is often
best used to break this cycle of sleep debt, whereas CBT
is used long-term to prevent recurrence, as evidenced by
several studies.4,7,8 Although most of the discussion here
has focused on primary insomnia, CBT also benefits
patients with secondary insomnia.9-17 However, little is
known about its usefulness for insomnia caused by jet
lag, acute stress, or shift work.2
Pre
Post
FU3
FU12
FU24
75
60
45
30
15
0
CBT
Med
Comb
Placebo
In this study, 78 adults with chronic primary insomnia were randomized to
receive CBT (ie, stimulus control, sleep restriction, sleep hygiene, and cognitive therapy), pharmacotherapy, both (Comb), or placebo. Outpatient
treatment lasted 8 weeks and follow-ups continued at 3, 12, and 24 months.
Efficacy is defined as a decrease in the number of minutes awake after sleep
onset, which is the sum of the duration of all awakenings between sleep
onset and final wake-up time.
CBT = cognitive-behavioral therapy; Comb = CBT and pharmacotherapy;
FU = follow-up.
Adapted with permission from Morin et al. JAMA.1999;281:991-999.4
Figure 2. Drugs Used to Treat Insomnia
Trazodone*
Zolpidem
Amitriptyline*
Mirtazapine*
Temazepam
Quetiapine*
Zaleplon
Clonazepam
Hydroxyzine*
Antidepressant
BZRA
BZD
Atypical antipsychotic
Antihistamine
0
1
2
3
Occurences, millions
*Not approved by the US Food and Drug Administration for this use.
BZD = benzodiazepine; BZRA = benzodiazepine-receptor agonist.
Adapted with permission from Walsh. Sleep. 2004;27:1441-1442.18
S1035

∠
PROCEEDINGS
acetylcholine, dopamine, and histamine). Medications
prescribed for insomnia work primarily by affecting 1
of 3 neurotransmitters: histamine, GABA, and melatonin. Although many drugs frequently are prescribed
in the attempt to treat insomnia (Figure 2),18 most do
not have a US Food and Drug Administration (FDA)
indication for this use.18
HISTAMINE
Histamine is an excitatory neurotransmitter, therefore, antihistamines cause sleepiness. Antihistamines
are the second most commonly used drug in the
United States to treat insomnia (after alcohol).
Antihistamines can be obtained over-the-counter
(OTC) or by prescription, but they do not have US
FDA approval for treating insomnia. Diphenhydramine is probably the most well-known antihistamine, but many patients also take Tylenol PM, which
is 25-mg diphenhydramine and 500-mg acetaminophen. These antihistamines are relatively inexpensive and, because they have no abuse potential,
they are not scheduled by the US Drug Enforcement
Administration (DEA). However, many patients mistakenly think that because these drugs are OTC, they
can safely take virtually limitless quantities for insomnia. However, these medications have an 8- to 15-hour
half-life, which leads to daytime sedation and potential
danger of overdose. Patients also can develop a tolerance to them over time.
Several antidepressants also have histamine as a secondary binding characteristic; these include trazodone
(used frequently to treat insomnia), paroxetine, mirtazapine, fluvoxamine, and, in general, tricyclic antidepressants (eg, clomipramine, amitriptyline, and
nortriptyline).19 However, these drugs also lack US
FDA approval for treating insomnia and also have
potential for side effects, which should be weighed
when creating a long-term treatment strategy for
insomnia. This is especially important in elderly
patients.
duce drowsiness and facilitate the onset and maintenance of natural-type sleep (ie, the person can be easily awakened and electroencephalography recordings
are similar to those with naturally occurring sleep).20
Barbiturates were the first drugs found to affect
GABAergic neurotransmission; however, the most
frequently prescribed and well known are the benzodiazepines. Most benzodiazepines are quickly
absorbed. The primary differences between them lie
in their relative elimination half-lives, which can
range from less than 4 hours to more than 1 week
(Figure 3).21-23 The variety of half-lives with these
drugs makes them especially useful for managing different types of insomnia, but also highlights the
importance of carefully documenting insomnia symptoms, such as difficulty falling asleep versus difficulty
staying asleep. Patients having trouble falling sleep
should use drugs with short half-lives, whereas
patients waking up after only a few hours would fare
better with intermediate to longer half-life drugs.
Patients often report increased total sleep time as the
litmus test for a good night’s sleep (eg, “I slept 8 hours
last night” or “I didn’t wake up once last night”). The
Figure 3. Benzodiazepines and Nonbenzodiazepines Have
a Wide Range of Half-lives
Zaleplon
1
Zolpidem
2
Triazolam*
3
Eszopiclone
Temazepam*
Estazolam
*
Quazepam*
γ-AMINOBUTYRIC ACID
Drugs that activate GABAergic neurotransmission
have been studied extensively, and several drugs with
this mechanism of action have indications for the
treatment of insomnia. Virtually all of these drugs
enhance GABAA receptor activity and are referred to as
sedative-hypnotics. Sedatives decrease activity, moderate excitement, and calm the recipient; hypnotics pro-
S1036
Flurazepam*
6
11
10– 24
39
74
Half -li fe, hrs
*Benzodiazepines.
Several commonly used benzodiazepine and nonbenzodiazepine γ-aminobutyric acid agonists and their half-lives are shown. Half-lives can extend to beyond
1 week for some drugs, such as medazepam, nordazepam, and prazepam.
Data from Dikeos and Soldatos.22
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PROCEEDINGS
longer the medication’s half-life, the greater the
opportunity for increasing total sleep time, and there
is less chance of wake after sleep onset. However, correct timing of the dose is important and requires close
patient monitoring to minimize the risk of driving (or
working) drowsy in the morning.
In fact, there are several limitations with using benzodiazepine and nonbenzodiazepine GABA receptor
agonists. For example, all of these medications are classified as schedule IV controlled substances by the US
DEA. Also, some of the side effects associated with
their use include psychomotor impairment, depressed
respiration, and amnesia. Patients taking these drugs
over a long period of time also can suffer from
rebound insomnia when the medication is stopped
and/or tolerance to the drugs over time. Also, overdose
is a potential danger with these drugs.
Nonbenzodiazepines are the most recently available drugs in this class. They include eszopiclone (indicated for sleep onset and maintenance, and the first
hypnotic to be approved without a short-term use limitation), zaleplon (indicated for sleep onset, but sufficiently short-acting to be taken late during the night),
and zolpidem (indicated for improving sleep onset and
total sleep time). Controlled-release zolpidem is
approved for treating insomnia associated with difficulty initiating and maintaining sleep.
dietary supplement. Ramelteon is a potent and selective melatonin receptor agonist and received US FDA
approval in July 2005 for sleep onset insomnia.
Importantly, it is not a scheduled drug by the US
DEA, it carries no risk of abuse or tolerance, and it
does not impact GABA or histaminic neurotransmission. It is the first drug in 35 years to act outside of
those 2 neurotransmitter systems.
Ramelteon acts on melatonin 1 (MT1) and melatonin 2 (MT2) receptors, which are heavily concentrated in the SCN.27 Given the key role of the SCN in
sleep regulation, agents with high affinity and selectivity for MT1 and MT2 receptors are rational targets in
the treatment of insomnia.27 Specifically, binding to
MT1 receptors could decrease SCN stimulatory output (the alerting signal). These effects are in addition
to the melatonin already available and active in the
body. With the alerting mechanism inhibited, the
“sleep switch” is able to turn on. Agonism of the MT2
receptors may help to entrain the circadian clock
through phase shifting, which could help adjust the
timing of sleep.27,28 To date, the most common side
effects observed are sleepiness, dizziness, and fatigue.
As with any other medication for the treatment of
insomnia, patients should avoid driving or operating
machinery for a few days until they know how the
drug will affect them the next day.
COMPLEMENTARY MEDICINE
Although an HCP need not endorse or reject complementary medicines for the treatment of insomnia,
it is important to be aware of what patients are consuming or even reading about these products. For
example, valerian root and kava kava are commonly
touted as insomnia treatments. The biggest potential
hazard with these treatments is lack of standardization
in their production (noted in a July 2001 New York
Times article by Nagourney).24 Both HCPs and consumers can check to see if a particular product has
been tested for content (www.consumerlab.com).
DRUGS UNDER INVESTIGATION
Also under investigation are several other new
drugs. Gaboxadol is GABA receptor agonist, but it
acts only on certain types of GABA receptors (ie, outside synaptic junctions of thalamic and cortical neurons), which are thought to play an important
regulatory role in the onset, maintenance, and depth
of the sleep process.29 Also in phase III clinical trials are
low-dose doxepin (a tricyclic antidepressant) and
indiplon (a short-acting benzodiazepine receptor agonist hypnotic).30-35
MELATONIN AGONIST
Recall that melatonin is one of the critical regulators of the circadian rhythm. Its secretion is controlled
by the suprachiasmatic nuclei (SCN), increasing as
drowsiness sets in, with maximal levels at approximately 3:00 AM to 4:00 AM.25,26 Melatonin has been
used to shift the sleep-wake cycle in people suffering
from jet lag or shift work insomnia. It is available as a
Johns Hopkins Advanced Studies in Medicine
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THE NURSE PRACTITIONER’S ROLE IN PRESCRIBING
The NP’s role in prescribing any of these medications is to match the insomnia symptom with the most
appropriate treatment option. However, each state has
its own prescriptive authority guidelines for NPs
regarding scheduled medications. Once the medication
is started, consistent follow-up is important to ensure
that the dosage meets the specific needs of the patient
and that behavioral interventions also are employed.
S1037
PROCEEDINGS
CONCLUSIONS
Behavioral therapy focuses on sleep restriction,
stimulus control, relaxation, and sleep hygiene education, whereas cognitive therapy restructures anxietyproducing or erroneous beliefs about sleep.
Medications treat 3 targets in sleep regulation: GABA,
histamine, and melatonin. A multifaceted approach to
treating insomnia appears to be most effective—one
that can provide immediate relief, allay patient fears
and anxiety that may have developed over sleeping,
and maintain these benefits over the long term.
Studies have shown that CBT is beneficial for “primary” and “secondary” insomnia, maintains benefits long
term, and when used with pharmacotherapy can
improve patient outcomes even further. The NP’s role
is to monitor and educate the patient and the bed partner, to ensure that sleep is a high priority in the household, and to maintain close follow-up. If medication is
required, the NP will ensure that the medication
matches the insomnia symptoms. Given the strength
of data regarding insomnia treatments, future research
questions include the timing of CBT versus pharmacotherapy (eg, concurrently or sequentially), optimal
treatment dosage (ie, timing and frequency of followup consultations), and whether maintenance treatment will enhance long-term outcomes.2,36
REFERENCES
1. Dement WC, Vaughan C. The Promise of Sleep. New
York, NY: Dell Publishing; 1999.
2. Morin CM. Contributions of cognitive-behavioral approaches to the clinical management of insomnia. Prim Care
Comp J Clin Psychiatry. 2004;4:21-26.
3. Morin CM, Beaulieu-Bonneau S, LeBlanc M, Savard J. Selfhelp treatment for insomnia: a randomized controlled trial.
Sleep. 2005;28:1319-1327.
4. Morin CM, Colecchi C, Stone J, et al. Behavioral and
pharmacological therapies for late-life insomnia: a randomized controlled trial. JAMA.1999;281:991-999.
5. Belanger L, Savard J, Morin CM. Clinical management of
insomnia using cognitive therapy. Behav Sleep Med.
2006;4:179-202.
6. Edinger JD, Wohlgemuth WK, Radtke RA, et al. Cognitive
behavioral therapy for treatment of chronic primary insomnia: a randomized controlled trial. JAMA.
2001;285:1856-1864.
7. Sivertsen B, Omvik S, Pallesen S, et al. Cognitive behavioral therapy vs zopiclone for treatment of chronic primary
insomnia in older adults: a randomized controlled trial.
JAMA. 2006;295:2851-2858.
S1038
8. Thase ME, Rush AJ, Manber R, et al. Differential effects of
nefazodone and cognitive behavioral analysis system of
psychotherapy on insomnia associated with chronic forms
of major depression. J Clin Psychiatry. 2002;63:493-500.
9. Currie SR, Wilson KG, Pontefract AJ, deLaplante L.
Cognitive-behavioral treatment of insomnia secondary to
chronic pain. J Consult Clin Psychol. 2000;68:407-416.
10. Dashevsky BA, Kramer M. Behavioral treatment of chronic
insomnia in psychiatrically ill patients. J Clin Psychiatry.
1998;59:693-699.
11. Jacobs GD, Benson H, Friedman R. Perceived benefits in a
behavioral-medicine insomnia program: a clinical report.
Am J Med. 1996;100:212-216.
12. Rybarczyk B, Stepanski E, Fogg L, et al. A placebo-controlled test of cognitive-behavioral therapy for comorbid
insomnia in older adults. J Consult Clin Psychol.
2005;73:1164-1174.
13. Edinger JD, Wohlgemuth WK, Krystal AD, Rice JR.
Behavioral insomnia therapy for fibromyalgia patients: a
randomized clinical trial. Arch Intern Med.
2005;165:2527-2535.
14. Savard J, Simard S, Ivers H, Morin CM. Randomized study
on the efficacy of cognitive-behavioral therapy for insomnia
secondary to breast cancer, part I: sleep and psychological
effects. J Clin Oncol. 2005;23:6083-6096.
15. McCurry SM, Gibbons LE, Logsdon RG, et al. Nighttime
insomnia treatment and education for Alzheimer’s disease:
a randomized, controlled trial. J Am Geriatr Soc.
2005;53:793-802.
16. Currie SR, Clark S, Hodgins DC, El-Guebaly N.
Randomized controlled trial of brief cognitive-behavioural
interventions for insomnia in recovering alcoholics.
Addiction. 2004;99:1121-1132.
17. Quesnel C, Savard J, Simard S, et al. Efficacy of cognitivebehavioral therapy for insomnia in women treated for nonmetastatic breast cancer. J Consult Clin Psychol.
2003;71:189-200.
18. Walsh JK. Drugs used to treat insomnia in 2002: regulatory-based rather than evidence-based medicine. Sleep.
2004;27:1441-1442.
19. Stahl SM. Essential Psychopharmacology. 2nd ed. New
York, NY: Cambridge University Press; 2000.
20. Charney DS, Mihic SJ, Harris RA. Hypnotics and sedatives.
In: Harman JG, Limbird LE, eds. Goodman & Gilman’s The
Pharmacological Basis of Therapeutics. 10th ed. New
York, NY: McGraw-Hill Publishing; 2001.
21. Pagel JF, Parnes BL. Medications for the treatment of sleep
disorders: an overview. Prim Care Companion J Clin
Psychiatry. 2001;3:118-125.
22. Dikeos DG, Soldatos CR. The pharmacotherapy of insomnia: efficacy and rebound with hypnotic drugs. Prim Care
Companion J Clin Psychiatry. 2002;4:27-32.
23. Eszopiclone [prescribing information]. Marlborough, Mass:
Sepracor Inc. Available at:
http://www.lunesta.com/PostedApprovedLabelingText.pdf.
Accessed August 31, 2006.
24. Nagourney E. Quality of valerian herbal sleep aid is criticized. New York Times. July 10, 2001. Available at:
http://query.nytimes.com/gst/fullpage.html?sec=health&res
Vol. 6 (10D)
■
November 2006
PROCEEDINGS
=9A0CE7D81038F933A25754C0A9679C8B63.
Accessed August 31, 2006.
25. Arendt J, Skene DJ. Melatonin as a chronobiotic. Sleep
Med. 2005;9:25-39.
26. Dubocovich MI, Rivera-Bermudez MA, Gerdin MJ, Masana
MI. Molecular pharmacology, regulation and function of
mammalian melatonin receptors. Front Biosci.
2003;8:1093-1108.
27. Claustrat B, Brun J, Chazot G. The basic physiology and
pathology of melatonin. Sleep Med Rev. 2005;9:11-24.
28. Liu C, Weaver DR, Jin X, et al. Molecular dissection of two
distinct actions of melatonin on the suprachiasmatic circadian clock. Neuron. 1997;19:91-102.
29. Ebert B, Wafford KA, Deacon S. Treating insomnia: current
and investigational pharmacologoical approaches.
Pharmacol Ther. 2006;epub ahead of print.
30. Hsu, T, Rogowski R, Roth T. Low-dose doxepin in the
treatment of primary insomnia. In: Program and abstracts
of the Associated Professional Sleep Societies 19th
Annual Meeting; June 18-23, 2005; Denver, Colo.
Abstract 0150.
31. Roth T, Zammit G, Scharf MB, et al. Efficacy and safety of
indiplon-IR in adults with chronic insomnia characterized by
prolonged nighttime awakenings with difficulty returning to
sleep. In: Program and abstracts of the Associated
Johns Hopkins Advanced Studies in Medicine
■
Professional Sleep Societies 19th Annual Meeting; June 1823, 2005; Denver, Colo. Abstract 0683.
32. Walsh JK, Roth T, Moscovitch A, et al. Efficacy and tolerability of Indiplon-IR in elderly patients with primary insomnia.
In: Program and abstracts of the Associated Professional
Sleep Societies 19th Annual Meeting; June 18-23, 2005;
Denver, Colo. Abstract 0681.
33. Lankford J, Lydiard R, Walsh JK, et al. Efficacy and tolerability of Indiplon-MR in elderly patients with chronic insomnia:
results of a double-blind, placebo-controlled 2-week trial. In:
Program and abstracts of the Associated Professional Sleep
Societies 19th Annual Meeting; June 18-23, 2005;
Denver, Colo. Abstract 0685.
34. Scharf MB, Black J, Hull S, et al. Long term efficacy and
tolerability of Indiplon-IR in the treatment of chronic insomnia: results of a double-blind placebo-controlled 3-month
study. In: Program and abstracts of the Associated
Professional Sleep Societies 19th Annual Meeting; June 1823, 2005; Denver, Colo. Abstract 0682.
35. Mendelson W. Pharmacologic advances in the treatment of
insomnia. Available at: http://www.medscape.com/viewarticle/508953. Accessed August 31, 2006.
36. Vaillieres A, Morin CM, Guay B. Sequential combinations of
drug and cognitive behavioral therapy for chronic insomnia:
an exploratory study. Behav Res Ther. 2005;43:1611-1630.
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