Reviews for Primary Care - Fall 2007 - (Page 49) Insomnia and Neurological Disorders Patients should be encouraged to exercise during the day, but not too close to the evening hours. Circadian Rhythm Disturbances Circadian rhythm disturbances (CRDs) are commonly seen in institutionalized elderly patients and in patients with neurodegenerative disorders.14,15,110,111 Factors that may disturb the circadian regulation of sleep in dementia can be divided in 2 groups: direct and indirect. The symptoms of insomnia and hypersomnia can reflect a primary circadian dysrhythmia. In this clinical setting, patients tend to sleep more during the day and be active more during the night. This increased motor activity at night is the major contributing factor to sig- Pharmacotherapy of Insomnia Specific pharmacotherapy for insomnia is discussed elsewhere in this series and is summarized in Table 2. For some patients with insomnia, a trial with short- to intermediate-acting benzodiazepines (eg, temazepam) or ramelteon (Rozerem™; Takeda Pharmaceuticals, Deerfield, IL) may be tried for a short period. For nocturnal wanderings or agitation and sundowning, a trial with small doses (0.5 to 1 mg) of haloperidol may be instituted. nificant caregiver distress. Direct mechanisms thought to contribute to CRDs in patients with AD and other dementing conditions are related to degenerative changes that take place in the SCN of the hypothalamus and are the result of decreased melatonin production in the pineal gland.112,113 Indirect mechanisms include medications prescribed for these patients that cause nocturnal confusion, or sundowning. Patients with AD are commonly affected by the irregular sleepwake rhythm (ISWR), which is characterized by a lack of discernable sleep-wake circadian rhythm. Instead of having a major sleep period, sleep Table 2 Potential Hypnotics for the Treatment of Insomnia in Neurological Patients* Agent Nonselective benzodiazepines Triazolam (Halcion®†) Nonbenzodiazepine, benzodiazepine receptor agonists Zolpidem (Ambien®‡) Zolpidem, extended release (Ambien® CR‡) Zaleplon (Sonata®§) Eszopiclone (Lunesta®||) Melatonin receptor agonist, specific MT1 & MT2 receptor agonist Ramelteon (Rozerem™¶) * † Dose (mg) Onset of Action (min) Half-life (hours) Active Metabolites 0.125-0.25 (0.125) 15-30 2-5 No 5-10 (5 in elderly) 6.25-12.5 (6.25 in elderly) 5-10 (5 in elderly) 1-3 (1-2 in elderly) Short Short Ultrashort Intermediate 2.8 2.8 1 5-7 None None None Yes 8 Short 2.6 Yes The number of sedating compounds occasionally used off label for sleep induction and maintenance is too large to list here. This table is restricted to drugs objectively shown to be safe and effective hypnotics. Pharmacia & Upjohn Company, Kalamazoo, MI. ‡ sanofi-aventis, Bridgewater, NJ. § Wyeth Pharmaceuticals, Inc., Philadelphia, PA. || Sepracor Inc., Marlborough, MA. ¶ Takeda Pharmaceuticals, Deerfield, IL. VOL. 1 NO. 1 2007 REVIEWS FOR PRIMARY CARE 49
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