Table 3.

Medications Commonly Used for Sleep Disturbance (FDA approved for insomnia unless indicated)

Pharmacologic Class	Usual Adult Dose (mg)	Onset (min)	Average 1/2 Life (hr)	General Comments
Benzodiazepines Triazolam (Halcion®) Oxazepam (Serax®) Temazepam (Restoril®) Flurazepam (Dalmane®)	0.125–0.25 10–30 7.5–30 15–30	15–30 30–60 45–60 60–120	2–4 5–10 8–17 48–100	Prototype class of hypnotics – supplanted by newer benzodiazepine receptor agonists (BZRAs) with shorter half-lives Cautious use in the elderly, hepatic insufficiency, untreated sleep apnea Side effects include tolerance, dependency, morning-after sedation, cognitive impairment, rebound insomnia
Non-Benzodiazepine Benzodiazepine receptor agonist Zaleplon (Sonata®) Eszopiclone (Lunesta®) Zolpidem (Ambien®) Zolpidem CR (Ambien CR®) Zolpidem tartrate sublingual (Edluar) Zolpidem tartrate mist (Zolpimist)	5–20 1–3 5–10 5–10 5–10 5–10	20 30 30 30	1–1.5 1.5–2.5 2.5–2.8 1.6–5.5	BzRAs have lower risk of rebound insomnia, tolerance, sleep architecture change, muscle relaxation compared with older benzodiazepines, most indicated for onset insomnia Zolpidem is available as generic medication and available in several FDA approved forms: oral, oral extended release, sublingual, mist (with similar drug absorption and pharmacokinetic profiles). Rare but widely publicized sleep-eating and sleep-walking incidents with zolpidem Extended dosing zolpidem CR has initial release and slow release throughout the night Reduced dosage of BzRAs is recommended for elderly patients
Melatonin receptor agonist Ramelteon (Rozeram®)	8	30	1–5	Ramelteon has advantageous safety profile, minimal abuse and dependence potential. Modest efficacy, associated with multiple drug and food interactions (avoid taking with or right after a high fat meal). Side effects include headache, fatigue, dizziness, nausea, respiratory infection. Cautious use in elderly and patients with hepatic impairment.
Antidepressants TCAb Amitryptline (Elavil®) Doxepin (Sinequan®) Doxepin (Silenor®) Serotonin Modulating Trazodone (Drsyrel®)	10–300 25–50 3–6 25–150	30–60 30–60 30 30–60	14–18 20–25 4–7	Despite widespread off label use, most antidepressants are not FDA approved for insomnia; exception: low dose doxepin (Silenor) FDA approved for onset and maintenance insomnia (March/2010) Antidepressants for insomnia may be clinically justified if sleep disturbance is concomitant with depression and doses to treat insomnia are typically below antidepressant dose TCAs suppress REM sleep, have many drug interactions and impair cognition and psychomotor performance, therefore use cautiously in the elderly Trazodone may increase slow wave sleep and sleep continuity; should not be taken with MAO inhibitors; Trazadone affects daytime performance, and is associated with cardiac arrythmias, orthostatic hypertension, priapism.
Antihistamines Diphenhydramine (Benadryl®) (in Tylenol PM) Doxylamine (Unisom®)	25–50 25	60–180 60–120	4–10.4 10	Antihistamines are not recommended for insomnia Diphenhydramine extends sleep duration but is associated with tolerance to hypnotic effect, residual daytime sleepiness, and anticholinergic effects (e.g., dry mouth, constipation, urinary retention and excess sedation, dizziness, confusion, delirium) Use with caution in the elderly and those with narrow-angle glaucoma. Chlorpromazine, promethazine and other older sedating antihistamines are not good choices due to their profound antimuscarinic effects.
Melatonin	Usual dose: 1–3 mg			Melatonin is an endogenous hormone released by the pineal gland in response to dim light onset in early evening (normally production < 0.3 mg per day); exogenous melatonin is available as OTC nutritional supplement (not FDA approved; recommended dose has not been established). Limited clinical trial data to support efficacy of exogenous melatonin for insomnia, however, clinically it is often used to mange insomnia and circadian rhythm disorders including jet lag. Significant variability in melatonin content in OTC preparations have been reported. 1 to 3 mg, one hour before bedtime is usually effective for insomnia. Individual effects have been reported; higher doses may cause anxiety and irritability, start with the lowest dose – close to amount produced by our bodies (0.3 mg).
Nutritional Supplements Kava, Valerian, Skullcap, Passionflower				Inconsistent evidence for effectiveness of most nutritional supplements. Some placebo controlled studies have demonstrated short-term, subjective improvement in insomnia with valerian. FDA regulation of manufacturing of supplements is lacking.

(Note: Not intended as a prescribing guide)

Note: TCA = Tricyclic Antidepressants, OTC = over the counter