Management
Nonpharmacologic Management of Sleep Disturbances
Pharmacologic Management of Sleep Disturbances
Management of sleep disturbances should focus on treatment of symptoms related
to the cancer and its treatment, and identification and management of
environmental and psychological factors. Treatment of the malignancy may
resolve the sleep disturbance. When sleep disturbances are caused by symptoms
of cancer or treatment, measures that control or alleviate symptoms are often
the key to resolving sleep disturbances. Management of sleep disturbances
combines nonpharmacologic and pharmacologic approaches individualized for the
patient.
Nonpharmacologic Management of Sleep Disturbances
The environment can be modified to decrease sleep disruption. Minimizing
noise, dimming or turning off lights, adjusting room temperature, and
consolidating patient care tasks to reduce the number of interruptions can increase the
amount of uninterrupted sleep.[1]
Other actions or interventions that may promote rest include the following:[2,3]
- Keeping the patient's skin clean and dry.
- Giving back rubs and/or massaging areas of the body to bring comfort to the patient (e.g., bony prominences, head and scalp, shoulders, hands,
and feet).
- Keeping bedding and/or surfaces of support devices (chairs and pillows) clean,
dry, and wrinkle-free.
- Ensuring adequate bedcovers for warmth.
- Regulating fluid intake to avoid frequent awakening for elimination.
- Encouraging bowel and bladder elimination before sleep.
- Promoting optimal bowel function (increased fluids, dietary fiber, and use of
stool softeners and laxatives).
- Using a condom catheter for nocturnal incontinence.
- Providing a high-protein snack 2 hours before bedtime (e.g., milk,
turkey, or other foods high in tryptophan).
- Avoiding beverages with caffeine and other stimulants, including dietary
supplements that promote metabolism changes and appetite suppression.
- Encouraging the patient to dress in loose, soft clothing.
- Facilitating comfort through repositioning and support with pillows as
needed.
- Encouraging exercise or activity no less than 2 hours before bedtime.
- Encouraging the patient to keep regular bedtime and awakening hours.
- Minimizing and coordinating necessary bedside contacts for inpatients.
Psychological interventions are directed toward facilitating the patient's
coping processes through education, support, and reassurance. As the patient
learns to cope with the stresses of illness, hospitalization, and treatment,
sleep may improve.[4] Relaxation exercises and self-hypnosis performed at
bedtime can help promote calm and sleep. Cognitive-behavioral
interventions that diminish the distress associated with early insomnia and
change the goal from “need to sleep” to “just relax” can diminish anxiety and
promote sleep.[5] Communication, verbalization of concerns, and openness
between the patient, family, and health care team should be encouraged.
Many people who experience insomnia have been found to practice poor sleep hygiene (such as smoking and drinking alcohol just before bedtime), which can exacerbate or perpetuate insomnia.[6] Therefore, a complete assessment of sleep hygiene (i.e., time in bed; napping during the day; intake of caffeine, alcohol, or foods that are heavy, spicy, or sugary; exercise; and sleep environment) and use of behavioral management strategies (i.e., fixed bedtime; smoking, dietary, and alcohol restrictions 4–6 hours before bedtime; and increased exercise) may prove effective in reducing sleep disturbance.
Pharmacologic Management of Sleep Disturbances
When sleep disturbances are not resolved with other supportive care measures,
the use of sleep medications on a short-term or intermittent basis may be
helpful. Prolonged use of sleep medications for persistent insomnia, however,
can impair natural sleep patterns (i.e., rapid eye movement [REM] deprivation) and alter physiologic
functions. Prolonged use (>1–2 weeks) of these medications may result in
tolerance, psychological and physical dependence, drug intoxication, and drug
hangover.[1,7]
A newer agent, zolpidem, has reportedly not been associated with tolerance,
dependence, sleep cycle alterations, or rebound insomnia. Zolpidem tartrate
(Ambien) is administered in doses of 5 mg to 10 mg, 30 minutes before bedtime. To
date, this medication has not been widely used or studied in cancer patients.
Benzodiazepines have been widely used in the management of sleep disturbances.
Used as an adjunct to other treatment for short periods of time, these agents
are safe and effective in producing natural sleep because they are less
disruptive of REM sleep than are other hypnotic agents. Benzodiazepines have
an antianxiety effect in low doses and a hypnotic effect in high doses.
Commonly used sleep aids are not well studied in cancer patients. A randomized,
double-blind, placebo-controlled trial of triazolam was carried out in a major
cancer center in women undergoing initial breast cancer surgery. The drug was
superior to placebo with regard to improved sleep and restfulness. The
remaining literature is sparse with regard to empirical studies and randomized
controlled trials of sleep aids and is mostly anecdotal.[8]
Benzodiazepines differ from each other in duration of action and
pharmacokinetics. Liver disease has less of an effect on the metabolism of
lorazepam, oxazepam, and temazepam than on the metabolism of other
benzodiazepines. Whereas long-acting agents may produce daytime hangover,
short-acting agents are more often associated with dependence, rebound
insomnia, early morning insomnia, daytime anxiety, and serious withdrawal
effects such as seizures.[4] The following general characterizations can be
made:
- Intermediate- and short-acting benzodiazepines are characterized by half-lives
of 4 to 24 hours.
- Short-acting benzodiazepines are characterized by the following:
- Few active metabolites.
- Rarely, accumulation with multiple doses.
- Minimal effect on drug clearance by age and liver disease.
- Long-acting benzodiazepines are characterized by the following:
- Half-lives longer than 24 hours.
- Pharmacologically active metabolites.
- Accumulation with multiple dosages.
- Impaired clearance in older patients and those with liver disease.
Nonbenzodiazepine sleep aids include antidepressants, antihistamines, and
antipsychotics. Antihistamines have been popular drugs for the management of
sleep disturbances among cancer patients. The anticholinergic properties of
antihistamines relieve nausea and vomiting as well as insomnia. These agents
must be used with caution because daytime sedation and delirium can occur,
especially in older patients. Tricyclic antidepressants such as amitriptyline or
doxepin (Sinequan) may be effective in patients who are not depressed as well
as those who are depressed. When given at bedtime, these sedating agents can
eliminate the need for an additional hypnotic. Low doses of tricyclic
antidepressants can be effective sleep agents and may be the treatment of
choice for insomnia in patients who have neuropathic pain and appetite loss
(e.g., doxepin 50–100 mg at bedtime; amitriptyline 25–100 mg at bedtime). In
low doses, trazodone (50–150 mg) can promote sleep and is often combined with
other antidepressants (e.g., fluoxetine 20 mg in the morning) in depressed
patients with insomnia. A unique antidepressant, mirtazapine (Remeron), has
been used clinically to treat depression and also induces sleep, stimulates
appetite, and can decrease nausea in low bedtime doses. The hypnotic effects of
marijuana (tetrahydrocannabinol or THC) are similar to conventional hypnotics
in reducing REM sleep; however, side effects experienced before sleep induction and
hangover make the use of THC less acceptable than benzodiazepines.[9]
Low-potency neuroleptics (e.g., thioridazine 10–25 mg) are useful in promoting
sleep in patients with insomnia associated with organic mental syndromes and
delirium. (Refer to the PDQ summary on Cognitive Disorders and Delirium for more information.)
Barbiturates are generally not recommended for the management of sleep
disturbances in cancer patients. Barbiturates have a number of adverse
effects, including the development of tolerance, and they also have a narrow
margin of safety.
Most hypnotics are effective initially but lose efficacy when used regularly,
and they can become a primary cause of sleep disturbances.[10]
Medications Commonly Used To Promote Sleep
Drug category
|
Medication
|
Hypnotic dose (route)
|
Onset (duration of action)
|
Benzodiazepines |
diazepam
(Valium) |
5–10 mg (capsule, tablet) |
30–60 min (6–8 h) |
temazepam
(Restoril) |
15–30 mg (capsule) |
60 min, minimum (6–8 h) |
triazolam
(Halcion) |
0.125–0.5 mg (tablet) |
30 min (peaks 1–1.5
h) |
clonazepam
(Klonopin) |
0.5–2.0 mg (tablet) |
30–60 min (8–12 h) |
Tricyclic
antidepressants |
doxepin (Sinequan) |
10–150 mg |
30 min |
amitriptyline
(Elavil) |
10–15 mg |
30 min |
nortriptyline
(Pamelor) |
10–50 mg |
30 min |
Chloral
derivatives |
chloral hydrate |
0.5–1.0 g (capsule, syrup, suppository) |
30–60 min (4–8 h) |
Second-generation
antidepressants
|
trazodone (Desyrel) |
25–150 mg |
30 min |
nefazodone
(Serzone) |
50–100 mg |
30 min |
mirtazapine
(Remeron) |
15–60 mg |
30 min |
Antihistamines
|
diphenhydramine
(Benadryl) |
25–100 mg (tablet, capsule, syrup) |
10–30 min (4–6 h) |
hydroxyzine
(Vistaril,
Atarax) |
10–100 mg (tablet, capsule, syrup) |
15–30 min (4–6 h) |
Neuroleptics |
thioridazine (Mellaril)
|
10–50 mg |
30–60 min |
chlorpromazine (Thorazine) |
10–50 mg |
30–60 min |
Other |
zolpidem
tartrate
(Ambien) |
5–20 mg |
30 min (4–6 h) |
zaleplon
(Sonata) |
10–20 mg |
30 min (4–6 h) |
Melatonin, a hormone produced by the pineal gland during the hours of darkness,
plays a major role in the sleep-wake cycle. Although further study is indicated,
melatonin may play an important role in the treatment of certain types of
chronic sleep disorders.[11,12] It is suggested that melatonin exerts a
hypnotic effect through thermoregulatory mechanisms. By lowering the core body
temperature, melatonin reduces arousal and increases sleep propensity.
Melatonin is likely to be an effective hypnotic agent for sleep disruption
associated with elevated temperature due to low circulating melatonin levels.
The combined circadian and hypnotic effects of melatonin suggest a synergistic
action in the treatment of sleep disorders related to the inappropriate timing
of sleep and wakefulness. Adjuvant melatonin may also improve sleep disruption
caused by drugs known to alter normal melatonin production (e.g., beta-blockers
and benzodiazepines).[11]
Melatonin replacement has been shown to improve sleep in children with
endocrine tumors that diminish the natural production of the hormone.[12]
This efficacy has not been shown beyond this particular study.
Melatonin may affect the way tumor cells respond to chemotherapy and radiation
therapy. Some studies in colon cancer and brain cancer suggest the effect of
melatonin on chemotherapy and on radiation therapy may be beneficial.[13] Not
enough is known, however, to assure patients on these therapies that melatonin
treatment for insomnia is safe. The use of melatonin to treat insomnia in
cancer patients is under evaluation. Because the effect of melatonin on
chemotherapy can vary, it is important for patients being treated with chemotherapy to
consult with their health care professionals before using melatonin.
Changes in sleep-wake patterns are among the hallmarks of biologic aging.[14]
Evidence suggests that circulating melatonin levels may be significantly lower
in physically healthy older people and in insomniacs than in age-matched
control subjects. In view of these findings, melatonin replacement therapy may
be beneficial in the initiation and maintenance of sleep in elderly patients.[15]
Melatonin replacement, however, has not been studied in older people with
cancer as a treatment for insomnia.
References
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Savard J, Morin CM: Insomnia in the context of cancer: a review of a neglected problem. J Clin Oncol 19 (3): 895-908, 2001.
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Page M: Sleep pattern disturbance. In: McNally JC, Stair JC, Somerville ET, eds.: Guidelines for Cancer Nursing Practice. Orlando, Fla: Grune and Stratton, Inc., 1985, pp 89-95.
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Kaempfer SH: Insomnia. In: Baird SB, ed.: Decision Making in Oncology Nursing. Philadelphia, Pa: B.C. Decker, Inc., 1988, pp 78-9.
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Berlin RM: Management of insomnia in hospitalized patients. Ann Intern Med 100 (3): 398-404, 1984.
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Horowitz SA, Breitbart W: Relaxation and imagery for symptom control in cancer patients. In: Breitbart W, Holland JC, eds.: Psychiatric Aspects of Symptom Management in Cancer Patients. Washington, DC: American Psychiatric Press, 1993, pp 147-71.
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Jefferson CD, Drake CL, Scofield HM, et al.: Sleep hygiene practices in a population-based sample of insomniacs. Sleep 28 (5): 611-5, 2005.
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Jacobsen PB, Massie MJ, Kinne DW, et al.: Hypnotic efficacy and safety of triazolam administered during the postoperative period. Gen Hosp Psychiatry 16 (6): 419-25, 1994.
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Hollister LE: Health aspects of cannabis. Pharmacol Rev 38 (1): 1-20, 1986.
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Hayter J: Advances in sleep research: implications for nursing practice. In: Tierney AJ, ed.: Recent Advances in Nursing: Clinical Nursing Practice. Edinburgh, Scotland: Churchill Livingstone, 1986, pp 21-43.
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Dawson D, Encel N: Melatonin and sleep in humans. J Pineal Res 15 (1): 1-12, 1993.
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Jan JE, Espezel H, Appleton RE: The treatment of sleep disorders with melatonin. Dev Med Child Neurol 36 (2): 97-107, 1994.
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Lissoni P, Meregalli S, Nosetto L, et al.: Increased survival time in brain glioblastomas by a radioneuroendocrine strategy with radiotherapy plus melatonin compared to radiotherapy alone. Oncology 53 (1): 43-6, 1996 Jan-Feb.
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Haimov I, Lavie L: Melatonin-a chronobiotic and soporific hormone. Arch Gerontol Geriatr 24 (2): 167-73, 1997.
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Haimov I, Lavie P, Laudon M, et al.: Melatonin replacement therapy of elderly insomniacs. Sleep 18 (7): 598-603, 1995.
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