Fast Fact and Concept #105: Insomnia - Pharmacological Therapies

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Title: Fast Fact and Concept #105: Insomnia - Pharmacological Therapies

Author(s): Michael Miller; Robert Arnold

Fast Fact #101: Insomnia: Patient Assessment and Fast Fact #104: Non-pharmacological Therapy for Insomnia reviewed assessment of insomnia and non-pharmacological therapy. This Fast Fact focuses on the pharmacological treatment of insomnia. Prior to pharmacological treatment, it is important to improve sleep hygiene and treat any contributing underlying medical conditions (e.g. depression, pain, worsening CHF or COPD).

Non-Specific Drug Treatment

Benzodiazepines have been successfully used for short term insomnia, although there are no systematic studies on long-term use and rare studies in palliative care. The mechanism of action is unclear with the drugs causing subjective rather than objective improvement in sleep. Most commonly used are temazepam (start 7.5 mg po qhs), flurazepam (15 mg po qhs), estazolam (0.5 mg po qhs) and triazolam (0.125 mg po qhs). The first three are medium half-life benzodiazepines (10-15 hours); triazolam has a short half-life (<12 hours). All three undergo hepatic metabolism; flurazepam and triazolam have active metabolites. Benzodiazepines have a high incidence of amnesia and rebound insomnia, particularly in anxious patients, and may cause paradoxical agitation, especially in the elderly. Other side effects include tolerance and dependence with long-term use and additive CNS and respiratory side effects when used with other drugs. Triazolam is metabolized by cytochrome P450 3A4 and thus has numerous drug-drug interactions.

Benzodiazepine receptor agonists of the g-aminobutryic receptor complex. They are rapidly absorbed, are liver metabolized, do not have active metabolites, and have low abuse potential. Zolpidem (5-10 mg) and Zaleplon (10-20 mg) are ultra-short acting agents that restore sleep in patients with nocturnal awakenings.

Antidepressants such as trazadone (25-100 mg), doxepin (10-50 mg), and imipramine 10-75 mg) are commonly used for insomnia due to their sedative properties.

Miscellaneous Sedative Hypnotics - Choral Hydrate has moderate short term efficacy but is more toxic than benzodiazepines. Barbiturates are effective in short term treatment, but tolerance develops rapidly. Once commonly used for insomnia, these drugs are no longer used except in rare circumstances.

Antihistamines/OTC drugs - Diphenhydramine or other classical anti-histamines have sedative properties, but they are generally not preferred in the elderly due to anticholinergic properties and drug interactions. Diphenhydramine (25-100mg) has been shown to increase sleep duration and quality; duration of action is 4-6 hours. Most over the counter products contain diphenhydramine or a similar sedating antihistamine, including products such as Unisom, Tylenol PM, and Nyquil.

Melatonin is used for circadian rhythm sleep disorders and is less effective for chronic insomnia.

Herbal remedies - In one study Valerian (oral extract 400-900 mg qhs) was as effective as oxazepam. The major side effects are hepatotoxicity, cardiotoxicity and delirium. There is less data regarding kava.

Drugs for specific sleep disorders Restless leg syndrome is treated with dopaminergic agents such as pergolide (start 0.05 and increase to .2-.5 mg taken in divided doses before bedtime). Side effects of pergolide include abdominal pain, nasal stuffiness, nightmares, and recurrence of symptoms earlier in the day. Other dopamine agonists such as bromocriptine, pramipexole, and ropinirole can also be used. Treatment of narcolepsy is beyond the scope of this Fast Fact.

Also See:
Fast Fact #101: Insomnia: Patient Assessment
Fast Fact #104: Non-pharmacological Therapy for Insomnia


Hirst, A; Sloan R. Benzodiazepines and related drugs for insomnia in palliative care. The Cochrane Database of Systematic Reviews. Volume 1. 2003.

Carlos H. Schenck, Mark W. Mahowald, and Robert L. Sack. Assessment and Management of Insomnia JAMA 2003 289: 2475-2479.

Rickels K. Morris RJ. Newman H. et al. Diphenhydramine in insomniac family practice patients: a double-blind study. Journal of Clinical Pharmacology. 23(5-6):234-42, 1983 May-Jun.

Creation Date: 1/2004

Format: Handouts

Purpose: Instructional Aid, Self-Study Guide, Teaching

Training: Fellows, 3rd/4th Year Medical Students, PGY1 (Interns), PGY2-6, Physicians in Practice
Specialty: Anesthesiology, Emergency Medicine, Family Medicine, General Internal Medicine, Geriatrics, Hematology/Oncology, Neurology, OB/GYN, Ophthalmology, Pulmonary/Critical Care, Pediatrics, Psychiatry, Surgery
Non-Physician: Nurses

ACGME Competencies: Medical Knowledge, Patient Care

Keyword(s): Constitutional

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