Drugs for isomnia

Treatment Guidelines from The Medical Letter® Published by The Medical Letter, Inc • 1000 Main Street, New Rochelle, NY 10801 • A Nonprofit Publication IN THIS ISSUE (starts on next page) Drugs for Insomnia .p 57 Important Copyright Message The Medical Letter® publications are protected by US and international copyright laws Forwarding, copying or any distribution of this material is prohibited Sharing a password with a non-subscriber or otherwise making the contents of this site available to third parties is strictly prohibited By accessing and reading the attached content I agree to comply with US and international copyright laws and these terms and conditions of The Medical Letter, Inc For further information click: Subscriptions, Site Licenses, Reprints or call customer service at: 800-211-2769 FORWARDING OR COPYING IS A VIOLATION OF US AND INTERNATIONAL COPYRIGHT LAWS Related articles since publication: Suvorexant (Belsomra) for Insomnia (March 2, 2015) The Medical Letter publications are protected by US and international copyright laws Forwarding, copying or any other distribution of this material is strictly prohibited For further information call: 800-211-2769 Treatment Guidelines from The Medical Letter® Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication Volume 10 (Issue 119) July 2012 www.medicalletter.org Table Some Hypnotics Page 58 Drugs for Insomnia RECOMMENDATIONS: Benzodiazepine receptor agonists, benzodiazepines, the melatonin agonist ramelteon and low doses of the antidepressant doxepin are effective and generally safe for treatment of insomnia The antidepressant trazodone is widely used for this indication, but convincing evidence of its efficacy in patients who are not depressed is lacking Over-the-counter antihistamines marketed as “sleepaids” are not recommended; they can cause next-day sedation, impairment of performance skills such as driving, and troublesome anticholinergic effects Pharmacological treatment of insomnia includes prescription drugs, non-prescription medications and “natural” remedies Behavioral changes are often needed as well.1 BENZODIAZEPINE RECEPTOR AGONISTS — Zolpidem (Ambien, and others) is the most widely prescribed hypnotic in the US It is available in immediate-release, extended-release, sublingual and oral spray formulations A low-dose sublingual formulation of zolpidem (Intermezzo) is the only hypnotic approved by the FDA for middle-of-the-night awakening.2 Zolpidem, zaleplon (Sonata, and others), and eszopiclone (Lunesta) are not structural benzodiazepines, but bind to benzodiazepine receptors They are believed to act through an agonist effect on GABA A receptor complexes located close to or coupled with benzodiazepine receptors All act rapidly to decrease sleep latency and not affect deep sleep; the primary differences between them are in their duration of action (see Table 1) Adverse Effects – These agents may impair performance in the morning, including driving Anterograde amnesia can occur Complex sleep-related behaviors may occur without conscious awareness Eszopiclone leaves some patients with an unpleasant taste Hallucinations have been reported Like the benzodiazepines, benzodiazepine receptor agonists are schedule IV controlled substances Withdrawal, dependence and abuse can occur Some reports have associated use of hypnotics, particularly zolpidem, with excess mortality and an increased risk of cancer.3 Drug Interactions – Zolpidem, zaleplon and eszopiclone are metabolized to some extent by CYP3A4 Concurrent administration with a CYP3A4 inhibitor, such as clarithromycin (Biaxin, and others), theoretically could increase the risk of toxicity, but at least with zolpidem and zaleplon, the effect appears to be clinically insignificant Potent inducers of CYP3A4, such as rifampin (Rifadin, and others), could decrease the effectiveness of these drugs Concurrent use of alcohol or other CNS depressants increases the risk of CNS depression BENZODIAZEPINES — Benzodiazepines shorten the time to onset of sleep and prolong the first two stages of sleep They slightly reduce the relative amount of deep non-rapid-eye-movement and REM sleep The primary differences between the benzodiazepines are in their duration of action (see Table 1) Adverse Effects – Benzodiazepines may impair nextday performance, including driving.4 In addition, complex sleep-related behaviors and anterograde amnesia, particularly with triazolam, may occur Aggressive behavior has also been reported.5 In elderly patients, benzodiazepines can cause weakness, impair coordination and cause an increased incidence of falls and hip fractures.6 Lethal overdose with oral benzodiazepines taken alone occurs rarely; fatalities almost always involve concurrent use of alcohol or other CNS depressants All benzodiazepines are schedule IV controlled substances Dependence, tolerance, abuse and rebound insomnia can occur Federal copyright law prohibits unauthorized reproduction by any means and imposes severe fines 57 Drugs for Insomnia Table Some Hypnotics Drug Onset of Action Benzodiazepine Receptor Agonists Zaleplon – generic rapid (15-30 min) Sonata (King) Zolpidem – immediate-release rapid (