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Sleep Disorders in the Elderly
Module 3
Brenda K. Keller, MD
Assistant Professor
Geriatrics & Gerontology
University of Nebraska Medical Center
Module 3
Pharmacological Treatments
Choose carefully due to risk of side effects
• FDA Approved
• Non-FDA Approved
• Benzodiazepines
• Herbal therapies
• Non-Benzo hypnotics- • Hormones/naturopath
Type I Gaba receptor
ic
agents
• Sedating
• Eszopiclone
antidepressants
• Rozerem
• OTC antihistamines
General precautions
• Start low, go slow
• Avoid q hs dosing
• Use only 2-3 weeks
Pharmacological Treatments
• Benzodiazepines
– Short acting
• Lorazepam
• Temazepam
– Long acting
Pharmacological Treatments
• Non-Benzo hypnotics• Type I Gaba receptor agents
– Zaleplon (Sonata)
– Zolpidem (Ambien)
Pharmacological Treatments
• Eszopiclone (Lunesta)
– Single isomer, nonbenzodiazepine
cyclopyrrolone
– Affects both onset and maintenance of sleep
Pharmacological Treatments
• Ramelteon (Rozerem)
– Selective melatonin type 1 and type 2
receptor agonist
– Targets receptors in the suprachiasmatic
nucleus
Pharmacological Treatments
• Herbal therapies
– Valerian
• Hormones/naturopathic
– Melatonin
Pharmacological Treatments
• Sedating antidepressants
– Trazodone
– Tricyclic antidepressant
– Mirtazapine
Pharmacological Treatments
• OTC antihistamines
– diphenhydramine
Summary
Post-test question 1
• A 78-year-old woman presents with conjugal
bereavement and a chief complaint of insomnia and
daytime fatigue. She describes morbid dreams that have
progressively worsened over the past 6 months following
the death of her spouse. Her Mini–Mental State
Examination score is 24/30. Sleep laboratory
(polysomnographic) studies show shortened period of
rapid-eye movement (REM) sleep onset latency,
increased REM density, and reduced total sleep time.
Which of the following medications would be the best
treatment in this case?
A.Zolpidem
B.Clonazepam
C.Mirtazapine
D.Donepezil
E.Thioridazine
Used with permission from: Murphy JB, et. Al. Case Based Geriatrics Review: 500 Questions and
Critiques from the Geriatric Review Syllabus. AGS 2002 New York, NY.
Correct Answer: C. Mirtazapine
• This case represents a common clinical presentation, that of spousal
bereavement and sleep complaints. Both the disturbing dreams
reported by the patient and her mild cognitive impairment add further
complexity to the case. Comorbid psychiatric disorders often
contribute to the development of insomnia, as will any condition,
such as grief, that results in psychologic arousal. Spousal
bereavement is associated with a high prevalence of depression
and associated sleep disturbance. Disorders of cognitive
impairment, including dementia and delirium, also contribute to
insomnia and disturbances of the sleep-wake cycle, including
nighttime wandering and delirium (ie, sundowning). In this case,
efforts were made using sleep electroencephalography to
distinguish major depression from other psychopathologic states.
The primary well-documented changes in sleep architecture include
shortened period of rapid-eye movement (REM) sleep onset latency,
increased REM density, reduced total sleep time, reduced sleep
efficiency, increased awakenings, increased slow-wave sleep, and a
shift of slow-wave sleep from the first non-REM cycle to the second.
The causes of these alterations are the subject of much speculation.
• Both major depression and aging result in increased
awakenings, reduced slow-wave sleep, and reduced
REM sleep latency. Older persons with depression have
more difficulty maintaining sleep than younger persons
or nondepressed older persons, and relatively reduced
slow-wave sleep appears to be a strong characteristic of
depression in all age groups. Unlike in a younger person
with depression, the occurrence of REM sleep in less
than 10 minutes after sleep onset seems to be most
characteristic of the depressed elderly patient. Indeed, it
appears that aging coupled with depression tends to
cause a precipitous reduction in REM sleep latency. The
degree of sleep disturbance may be somewhat related to
the severity of depression. Associated cognitive
difficulties are also related to the degree of sleep
fragmentation caused by depression. Consideration of
these findings suggests that the most useful medication
in treating the patient in this case is mirtazapine.
• Mirtazapine is an effective antidepressant that tends to be sedating
at low doses (15 mg). If this sedation is a problem, increasing the
dose (eg, to 30 or 45 mg) is beneficial since at higher doses, more
noradrenergic stimulation occurs. Zolpidem, although a useful
sedative in elderly patients, is not the best choice for the patient in
question, since she has an underlying depression. Similarly,
clonazepam may be useful in the treatment of disordered sleep
movement but is also not effective for depression. Donepezil is
useful in the treatment of cognitive symptoms, and in this case
further evaluation for dementia is indicated following the resolution
of the depressive symptoms. It is quite possible that the cognitive
impairment will reverse with antidepressant therapy, in which case
pseudodementia may be diagnosed in retrospect. Thioridazine is not
a useful drug for this patient. Antipsychotic agents are primarily
useful in treating patients with psychosis and severe nonpsychotic
agitation. Thioridazine is a low-potency agent with potential for
anticholinergic side effects, daytime drowsiness, and the
development of orthostatic symptoms, all significant concerns in the
elderly age group.
Post-test question 2
• An 83-year-old woman who has hypertension and
osteoarthritis has a 3-week history of difficulty falling
asleep and several awakenings throughout the night.
Her symptoms are attributed to acute psychosocial
stressors. You determine that a short course of a
hypnotic agent is indicated. Which of the following drugs
is most appropriate?
A. Amitriptyline
B. Diphenhydramine
C. Melatonin
D. Triazolam
E. Zolpidem tartrate
Correct Answer: E. Zolpidem tartrate
• Zolpidem is a nonbenzodiazepine hypnotic that has a
desirable pharmacologic profile for older patients with
medical illnesses. It is effective both in inducing and
maintaining sleep. Onset of effect is 30 minutes to 1
hour; it has no active metabolites and is eliminated
rapidly (half-life of 2.5 hours). The sedative advantages
over short-acting benzodiazepines may not be significant
in short-term use. However, lack of tolerance and
withdrawal phenomenon are advantageous, particularly
for long-term administration. Zolpidem is not associated
with memory effects, daytime sleepiness, or drug-drug
interactions (except with alcohol). Generally, this patient
could be expected to have a better outcome if
pharmacotherapy is combined with behavioral therapy.
Tricyclic antidepressants often are used for insomnia in
older patients.
• Amitriptyline is the most sedating and most frequently prescribed,
although it is associated with anticholinergic and other adverse
effects, such as orthostatic hypertension. The disadvantages of
using tricyclic antidepressants usually outweigh any therapeutic
advantage. Diphenhydramine and other antihistamines may improve
acute insomnia, but even low doses sometimes are associated with
impaired daytime functioning. Diphenhydramine also has
anticholinergic effects and may be associated with delirium,
especially when administered with other medications that act on the
central nervous system. Melatonin has received much attention as
an over-the-counter sleep aid. Although age-related changes in its
secretion cycle may contribute to insomnia in healthy older adults,
supplementation is of unknown therapeutic value in patients such as
this. Moreover, studies suggest that it is not useful as a hypnotic
agent. Triazolam is an ultra–short-acting benzodiazepine hypnotic.
Its advantages are rapid onset and minimal adverse effects,
including little hangover. However, it may be associated with early
morning rebound insomnia and anxiety. Of greater concern is the
risk of tolerance and dependence and some risk of anterograde
amnesia. Less common adverse effects include disinhibition and
delirium or withdrawal, especially at higher dosages. End