Table 3:   Drug management of Insomnia

Table 3.   Drug management of Insomnia

Heterocyclics: Doxepin is FDA approved for sleep maintenance insomnia; Trazodone and Mirtazapine are not FDA approved for treatment of insomnia. Less evidence than the non-BRZA but several randomized controlled trials provide evidence of effectiveness vs placebo or treatment as usual. More research is needed regarding long-term efficacy. Less risk for habituation or tolerance than non-BZRA. [59–63]
Drug	Dose/titration	Important adverse effects/precautions
Trazodone	7.5–45mg at bedtime	Not FDA approved;   off-label for sleep-onset insomnia. Side effects:   drowsiness, dizziness, dry mouth, increased appetite, weight gain, constipation, asthenia, and increased risk of hyponatremia. Use with caution:   in patients with renal impairment, hepatic disease, hypercholesterolemia, and hyperglyceridemia.
Doxepin	3–6mg at bedtime	FDA approved for sleep maintenance insomnia. Side effects:   drowsiness, dizziness, headache. May exacerbate restless legs, periodic limb movements, and REM sleep behavioral disorders. Contraindications:   taking an MAOI, untreated narrow-angle glaucoma, severe urinary retention, and long QT syndrome.
Melatonin-receptor agonists: FDA approved for sleep onset insomnia. No habituation or tolerance risk and fewer morning adverse effects. May be less effective for reducing SOL in older adults. [39,58,59,64,65]
Drug	Dose/titration	Important adverse effects/precautions
Ramelteon	8mg at bedtime	FDA approved for sleep-onset insomnia. Side effects:   drowsiness, dizziness, and interaction with fluvoxamine. Use with caution:   in patients with mild-moderate hepatic disease. Also be cautious with patients with schizophrenia, bipolar disorder, and major depression, as hallucinations have been reported. Increased risk of seizure activity related to melatonin and melatonin-receptor agonists. Avoid alcohol with ramelteon. Avoid activities that require concentration, such as driving.
Nonbenzodiazepine receptor agonists: While the following medications are FDA approved for sleep-onset and/or sleep-maintenance insomnia, they are recommended to be avoided by the American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. It is recommended that any use of these medications be done on an individual basis. No specific agent is recommended as preferable; each has shown to have positive effects on SOL, WASO, and/or TST in randomized controlled trials vs placebo or TAU. Patients may respond differently to different agents in this class. Factors to consider include symptom pattern, past response, cost, and patient preference. While there is evidence for long-term use for some agents, use >90 days should be avoided if possible. [39,50,56,58,64,66–73]
Zolpidem Zolpidem CR Sublingual Zolpidem Zaleplon Eszopiclone	5mg at bedtime 6.25mg at bedtime 1.75mg at bedtime or during nighttime awakenings (Intermezzo) 5mg at bedtime (Edluar) 5–10mg at bedtime 1–2mg at bedtime	Side effects:   drowsiness, dizziness, headache, amnesia, and GI symptoms. Eszopiclone is associated with unpleasant taste and dry mouth. Avoid driving or performing tasks requiring mental alertness and concentration. Risk for next-morning impairment is higher if less than 7–8 hours of sleep opportunity when taking at sleep onset; increased risk of impairment if <4 hours of sleep opportunity when taking for sleep maintenance insomnia. Patients should avoid alcohol when using these drugs. Patients with dementia, cognitive impairment, or delirium and with history of falls or fractures are at increased risk for adverse CNS effects.
Note: SOL = sleep onset latency TAU = treatment as usual TIB = time in bed TST = total sleep time TWT = total wake time WASO = wake after sleep onset.