Sleep Disorders in the Elderly Module 3

1. Sleep Disorders in the ElderlyModule 3 Brenda K. Keller, MD Assistant Professor Geriatrics & Gerontology University of Nebraska Medical Center

2. FDA Approved Benzodiazepines Non-Benzo hypnotics- Type I Gaba receptor agents Eszopiclone Rozerem Non-FDA Approved Herbal therapies Hormones/naturopathic Sedating antidepressants OTC antihistamines Module 3Pharmacological Treatments Choose carefully due to risk of side effects

3. General precautions • Start low, go slow • Avoid q hs dosing • Use only 2-3 weeks

4. Pharmacological Treatments • Benzodiazepines • Short acting • Lorazepam • Temazepam • Long acting

5. Pharmacological Treatments • Non-Benzo hypnotics- • Type I Gaba receptoragents • Zaleplon (Sonata) • Zolpidem (Ambien)

6. Pharmacological Treatments • Eszopiclone (Lunesta) • Single isomer, nonbenzodiazepine cyclopyrrolone • Affects both onset and maintenance of sleep

7. Pharmacological Treatments • Ramelteon (Rozerem) • Selective melatonin type 1 and type 2 receptor agonist • Targets receptors in the suprachiasmatic nucleus

8. Pharmacological Treatments • Herbal therapies • Valerian • Hormones/naturopathic • Melatonin

9. Pharmacological Treatments • Sedating antidepressants • Trazodone • Tricyclic antidepressant • Mirtazapine

10. Pharmacological Treatments • OTC antihistamines • diphenhydramine

11. Summary

12. 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.

13. 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.

14. 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.

15. 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.

16. 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

17. 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.

18. 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