Sleeping Pills - Sedative Hypnotics Overview

Sleep aids (sedative hypnotics) reduce the length of time it takes to fall asleep or increase sleep duration. They are usually taken at bedtime, although some newer ones may be appropriate for use on an "as needed" basis, whenever symptoms occur.

There are different classes of sedative hypnotics. The most effective sleep aids are benzodiazepines and a newer class known as non-benzodiazepine benzodiazepine receptor agonists.

Sleeping pills may be taken when:

• The cause of insomnia is determined and the hypnotic is a good choice.
• Poor sleep seriously affects daily activities.
• Behavioral approaches have proven ineffective and the person is reluctant to try them.
• Insomnia is transient or short-term (e.g. traveling across time zones).

Treatment should be short-term, if used nightly or intermittent, if used long-term. And should be used only in combination with good sleep practices and behavioral approaches.

Disadvantages

• Sleep aids don't treat the causes of insomnia
• Development of tolerance and dependence
• Most hypnotics lose effectiveness after 4-6 weeks of nightly use
• Potential interactions with alcohol or other substances
• Withdrawal symptoms
• Rebound insomnia

Advantages

• Effective for transient or acute insomnia
• Work fast in improving sleep in the short-term
• May be appropriate for chronic insomnia in people who do not respond to CBT (cognitive-behavioral therapy) or for whom CBT is not available
• Easy to use and widely available
• May prevent transient or acute insomnia form developing into chronic form

Benzodiazepines

Benzodiazepines, also referred to as benzodiazepine receptor agonists, were once the most commonly used sedative hypnotics. Benzodiazepines were originally developed in the 1960s.

The main difference among benzodiazepines is the length of effect, which depends on a half-life. Long-acting benzodiazepines cause a lot of next morning sedation. Short-acting benzodiazepines are particularly useful for travelers who want to reduce the effects of jet lag. Long-term use (sometimes even after a few weeks) is associated with dependence and withdrawal syndrome.

Long acting benzodiazepines include: flurazepam (Dalmane), clonazepam (Klonopin), quazepam (Doral).

Medium- to short-acting benzodiazepines include triazolam (Halcion), lorazepam (Ativan), alprazolam (Xanax), temazepam (Restoril), oxazepam (Serax), prazepam (Centrax), estazolam (ProSom), and flunitrazepam (Rohypnol).

Benzodiazepines are potentially dangerous when used in combination with alcohol, and have potential for interactions with other substances.

Rebound insomnia, the most common withdrawal symptom, usually occurs on the first night and sometimes the second night after stopping benzodiazepine. In some cases people may experience the return of original severe insomnia. Rebound insomnia is less common with long-acting benzos.

Non-Benzodiazepines

In the late 1980s a new class known as non-benzodiazepine benzodiazepine receptor agonists was introduced for the treatment of insomnia. These hypnotics are as effective as the benzodiazepines in promoting sleep. Both benzodiazepines (BZD) and non-benzodiazepines (non-BZD) act on GABA-A receptor sites in the brain. However, non-BZD are believed to have very low risk of abuse or dependence and fewer side effects.

From an efficacy standpoint, there are no clinical trials that show non-BZDs are more effective than the BZDs.

These hypnotics are very effective for preventing jet lag, however zolpidem (Ambien) should not be used on flights less than 7 - 8 hours. They also may be helpful for people with concomitant mood disorders, such as depression.

The risk for dependence, tolerance, withdrawal symptoms, and rebound insomnia is lower with non-benzodiazepines than with benzodiazepines. Also, non-benzodiazepines generally cause less disruption of sleep architecture.

Ramelteon (Rozerem)

Ramelteon was approved by the FDA in July 2005. It is a novel hypnotic known as the melatonin receptor agonist.

Ramelteon works by mimicking the actions of melatonin in the body. Melatonin is a hormone released by the brain that is believed to be important in the sleep-wake cycle. In clinical studies Ramelteon has not demonstrated potential for abuse, withdrawal syndrome, or rebound insomnia and so it doesn't have a controlled designation. All other sleep aids have a Schedule IV designation, indicating a low, yet recognizable risk of abuse/addiction.

Rozerem may be appropriate for adolescents, who don't usually do well on benzodiazepines. It may be particularly useful for elderly people who have reduced melatonin and trouble falling asleep.

Rozerem is not a choice for severe insomnia. It may be added on to other sleeping pills when they are not fully effective.

Zolpidem (Ambien)

Zolpidem (Ambien) is one of the most widely used sleep aids.

Large study demonstrated that zolpidem may be used on an as-needed basis1. After 3 weeks, two-thirds of the patients taking zolpidem this way were able to reduce their intake by more than 25% retaining improvements in sleep.

Zolpidem (Ambien) has a rapid onset of action and a half-life of only 1.5- 2.5 hours. This means that it may be taken later in the night when having trouble falling asleep and not worrying about residual cognitive impairment the next morning. Ambien decreases sleep latency and increases total sleep time. Unlike nonselective benzodiazepines, it does not decrease REM sleep.

Ambien could be less useful if you tend to wake up frequently in the middle of the night.

Zaleplon (Sonata)

Zaleplon (Sonata) is the shortest-acting non-benzodiazepine. Its half-life is just one hour. That means you can try to fall asleep on your own. Then, if you're still staring at the clock at 2 a.m., you can take it and not feel drowsy in the morning. Zaleplon takes effect within 30 minutes and may be taken at bedtime or later as long as you can sleep for at least 4 hours. However, if you tend to wake during the night, Sonata in not for you.

Sonata appears to be more safe than other hypnotics and may be particularly useful for patients in the younger and older age groups.

Eszopiclone (Lunesta)

Eszopiclone (Lunesta) is a new non-benzodiazepine approved by the FDA in December 2004. It may help persons who have trouble falling asleep, wake frequently during the night, or wake up too early in the morning. Eszopiclone is related to zopiclone (Imovane), which has been used for many years in Europe.

Unlike other hypnotics, Lunesta can be taken on a long-term basis. In clinical trials, patients used Lunesta for up to 6 months.

Of all the new sleeping pills approved so far, Lunesta has the longest half-life (about 6 hours) and is approved for sleep maintenance.

Comparison of Non-Benzodiazepines

Other sleep aids

The sedating antidepressants trazodone (Desyrel), amitriptyline (Elavil), nortriptyline (Pamelor), and doxepin (Sinequan) have been used for many years to promote sleep. They are non-addictive and do not produce tolerance.

References

• 1. Hajak G, Cluydts R, Declerck A, Estivill SE, Middleton A, Sonka K, Unden M. Continuous versus non-nightly use of zolpidem in chronic insomnia: results of a large-scale, double-blind, randomized, outpatient study. Int Clin Psychopharmacol. 2002 Jan;17(1):9-17.

Last updated: May 2011