What are the prescription and non-prescription medications available to treat insomnia, and what are their dosages, adverse reactions and efficacy rates?

Medications to Treat Insomnia

Hypnotic agents are used in the treatment of insomnia. There are several classes of hypnotics including benzodiazepines, nonbarbiturate – nonbenzodiazepines, antidepressants, and antihistamines. A list of the agents in each class and their dosages, efficacy, and adverse reactions is provided.

Benzodiazepines

The benzodiazepines are drug of choice and the most widely prescribed agents for insomnia. The agents above are FDA approved for insomnia, but other agents are also effective. These agents decrease the latency to sleep onset and number of awakenings.

Adverse Effects

Daytime effects that may carry over include excessive drowsiness, psychomotor incoordination, decreased concentration, and cognitive deficits. The benzodiazepines with intermediate to long elimination half lives have a greater potential for causing carry over effects. Triazolam and flurazepam have the shortest half live and would therefore decrease the chance of carry over sedation and other CNS effects. Larger doses are also associated with an increased risk for carry over effects. Other side effects that are possible include anterograde amnesia, confusion, agitation, and hallucinations. Elderly patients are at an increased risk for side effects.

Efficacy

Efficacy with continuous use for one month has been shown with flurazepam, quazepam, and temazepam. Tolerance to triazolam has been demonstrated as early as two weeks continuous use. Estazolam has shown efficacy with use up to 12 weeks. Use of low dose benzodiazepines longer than six months has been associated with a loss of efficacy and worsening of sleep. Short acting benzodiazepines are recommended for patients who have difficulty initiating sleep and require daytime alertness. Intermediate acting agents are recommended for patients who have difficulty maintaining sleep or early morning awakening.

Nonbarbiturate – Nonbenzodiazepines

Zolpidem is indicated for use in the short-term management of insomnia, limiting therapy to seven to ten days. The usual dose is 10mg at bedtime. If sleep aid is needed for greater than two to three weeks, the patient should be reevaluated.

Adverse Effects

The most commonly reported adverse effects include dizziness, nausea, vomiting, confusion and headache. Other adverse effects that have been reported include fatigue, anxiety, drowsiness, irritability, hangover, constipation, and abdominal pain. Hallucinations have been reported in elderly patients and patients taking concomitant SSRIs.

Efficacy

Zolpidem is efficacious in the short-term treatment of insomnia in adults. Compared to trazadone, zolpidem demonstrated greater efficacy. Zolpidem has comparable efficacy to triazolam, zaleplon, and midazolam.

 

 

Zaleplon reduces sleep latency in patients with primary insomnia; it does not increase total sleep time or decrease the number of awakenings. A 5mg dose may be initiated in low weight individuals or the elderly. Otherwise, start with 10mg at bedtime. Two claims for zaleplon are its lack of hangover-effect potential and minimal-to-absent rebound insomnia upon discontinuation.

Adverse Effects

Predominant adverse effects are headache, somnolence, and dizziness. Use is not recommended in patients with severe hepatic impairment, or in pregnant or lactating women. Amnesia, anxiety, depersonalization, hallucinations, hyperesthesia, paresthesia, tremor, vertigo and malaise have occurred in 1% or more of patients treated with zaleplon. Other adverse effects that have been reported include psychomotor impairment, rebound insomnia, anorexia, nausea, and myalgia.

Efficacy

Efficacy is primarily limited to reducing sleep latency. Total sleep time or number of awakenings may not be significantly affected, and greatest usefulness of the drug is in patients with sleep initiation disorders. The longest duration of therapy in clinical studies was nightly administration for 28 days. Zaleplon has demonstrated comparable efficacy to zolpidem, flurazepam, alprazolam, and triazolam.

 

Chloral Hydrate

Chloral hydrate is FDA approved for the short-term treatment of insomnia. The usual dose is 500 to 1000mg, 15 to 30 minutes before bedtime. This agent is available in oral dosage as well as rectal suppository. Chloral hydrate should be avoided in patients with renal failure and should be given in a dose of 250mg QHS in geriatric patients.

Adverse Effects

Arrhythmias, hallucinations, disorientation, nausea, vomiting, and diarrhea are commonly reported adverse effects.

Efficacy

Chloral hydrate has been shown to be efficacious in short-term treatment of insomnia. When compared to triazolam for treatment of insomnia, triazolam was superior in efficacy and preferred over chloral hydrate. No other comparative efficacy is reported.

Antidepressants

Trazodone (DesyrelÒ )

Trazodone is primarily used in the treatment of depression and anxiety disorders but has shown some efficacy in insomnia. Trazodone has been given in bedtime doses of 50 and 100mg.

Adverse Effects

Changes in blood pressure, syncope, tachycardia or palpitations, and shortness of breath have been reported in 1% of patients or more. Trazadone may be arrythmogenic in patients with preexisting cardiac disease. Dizziness, fatigue, nausea and vomiting have been reported commonly. Urinary retention, sexual dysfunction and musculoskeletal aches and pain are also possible. It is important to remember that these side effects are reported in clinical trials and there are very few clinical trials examining the use of trazodone in insomnia. These side effects therefore are reported in patients taking larger, more frequent doses.

Efficacy

Compared to zolpidem, trazodone was less effective in treating insomnia, but superior to placebo. It has been beneficial in patients with sleep disorders accompanied by a depressive state.

 

 

 

Antihistamines

Diphenhydramine (BenadrylÒ )

Diphenhydramine is FDA approved for insomnia and is effective for occasional sleeplessness. The recommended hypnotic dose is 50mg QHS; this dose may be increased to 100mg. As the dose increases, the risk of side effects increases.

Adverse Effects

The most common adverse effects include sleepiness, sedation, dizziness, and disturbed coordination. Anticholenergic side effects that may occur include tremors, nervousness, irritability, palpitations, dry mouth, nose and throat, thickening of bronchial secretions, blurred vision, urinary retention, tachycardia, and constipation.

Efficacy

Diphenhydramine has been shown to decrease latency and number of awakenings and increase the duration of sleep. Its efficacy is comparable to pentobarbital.

Doxylamine (UnisomÒ )

Doxylamine is a nonprescription antihistamine used to treat insomnia. The usual dose is 25mg 30 minutes prior to bedtime; this dose can be increased to 100mg. Doxylamine has been shown to decrease sleep latency and improve the duration of sleep.

Adverse Effects

Drowsiness and hangover or residual sedation have been reported with use of doxylamine. Occasional anticholenergic side effects have also been reported.

Efficacy

Doxylamine is effective in the short-term treatment of insomnia. Doxylamine has hypnotic effects comparable to flurazepam, secobarbital, and pentobarbital. It also comparable to diphenhydramine but has a longer half-life and may have residual effects.

 

Resources:

1. MICROMEDEX

2. Kirkwood CK, Sood RK. Sleep Disorders. In: Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, editors. Pharmacotherapy: a pathophysiologic approach. 4^th Edition. Stamford, CT: Appleton & Lange, 1999. P.1479-1483.