ADVANCING YOUR PRACTICE

You’re getting sleepy: Drugs to treat insomnia
By Jennifer M. Belavic, PharmD

About one half of the adult population in the United States reports occasional bouts of insomnia, defined as difficulty falling asleep, staying asleep, or sleep of poor quality; 10% to 15% have chronic insomnia. Of these, about 2% to 6% use drugs to help them sleep.

Stay awake!
Insomnia is divided into three categories: transient, short-term, and chronic. Transient insomnia lasts only one to three nights; short-term insomnia occurs for three nights to 1 month; and chronic insomnia lasts for more than 1 month. Insomnia causes problems with social and occupational performance, comorbidities, healthcare costs, and an individual's quality of life, as well as increased use of drugs and perceived poor health. The risk factors associated with the increased incidence of insomnia include age (older people are affected more often), gender (women are more likely to be affected than men), medical or psychiatric illness, shift work, unemployment, marital status, body weight, and a sedentary lifestyle.

Diagnosing insomnia is a multifaceted process (see Criteria for diagnosing insomnia). Once the type of insomnia is diagnosed, treatment can begin.

When it comes to treating insomnia, goals include improvement of sleep quality and quantity, improvement of daytime function, and therapy that causes the least amount of adverse reactions. Both nonpharmacological and pharmacological treatment options are used to manage insomnia. Nonpharmacologic options are usually recommended as first-line treatments and include sleep hygiene education, muscle relaxation, biofeedback, cognitive therapy, and yoga. If those don't work, pharmacological options are tried. In this article, we'll focus on pharmacological options.

Treating insomnia
The most commonly used drugs to treat insomnia are over-the-counter drugs such as diphenhydramine (Benadryl) and doxylamine (Unisom). The most commonly used prescription drugs in the treatment of insomnia are benzodiazepines, nonbenzodiazepines, melatonin-receptor agonists, and antidepressants. Some individuals may use natural supplements to relieve their symptoms as well.

Benzodiazepines were introduced in the 1970s and became the drugs of choice for the treatment of insomnia by replacing older agents, including barbiturates, bromide, and chloral hydrate. Currently available benzodiazepines approved by the FDA to improve sleep quality include estazolam (Prosom), temazepam (Restoril), triazolam (Halcion), and flurazepam (Dalmane). They work by reducing sleep-onset latency (the time it takes to fall asleep), nocturnal awakenings, and rapid eye movement (REM) sleep. Due to their half-lives and duration of action, the benzodiazepines are able to increase an individual's total sleep time by decreasing the amount of time he may wake up during the night.

Benzodiazepines inhibit the gamma-aminobutyric acid (GABA) receptor complex and cause sedation, anterograde amnesia, anxiolysis (minimal sedation), and muscle relaxation.

Short-term use (less than 4 weeks) of benzodiazepines is relatively safe and effective. Long-term use isn't recommended, however, because patients may develop dependence and an increased chance of experiencing adverse reactions such as drowsiness, dizziness, and headache.

Benzodiazepine withdrawal may cause anxiety, depression, rebound insomnia, perceptual changes, nausea, nightmares, intense dreams, and poor memory consolidation. Benzodiazepine withdrawal can occur anywhere from a few hours of taking the first dose to 3 weeks after discontinuing the drug, depending on whether it's a short- or long-acting agent.

Patients with respiratory disorders shouldn't take benzodiazepines because they can cause respiratory depression. Caution should be taken with their use in older patients and in those with a history of substance abuse.

Nonbenzodiazepines were developed to replace benzodiazepines because they have fewer adverse reactions. There are three agents currently available in this category: zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta). Nonbenzodiazepines are more selective for the alpha1-subunit of the GABA receptors, leading to fewer adverse reactions.

Indicated for the short-term treatment of insomnia, zolpidem binds selectively to the alpha1-subunit of GABA receptors. The patient experiences strong sedative and hypnotic effects without the unwanted anxiolytic, muscle-relaxant, and anticonvulsant effects of benzodiazepines. Zolpidem has a short duration of action with a rapid onset, so it's often used to treat sleep-onset insomnia. Adverse reactions include drowsiness, dizziness, headache, rash, and gastrointestinal disturbances.

Zaleplon is used for short-term treatment of insomnia. It works by selectively binding to the alpha1-subunit of GABA receptors. Zaleplon decreases sleep-onset latency and has shown benefit in individuals who have difficulty falling asleep and maintaining sleep. This medication isn't associated with the tolerance, rebound insomnia, or hangover effect that's seen with benzodiazepines. Adverse reactions include dizziness, headache, anxiety, amnesia, malaise, and visual disturbances.

Eszopiclone can be used longer than 35 days to treat sleep-onset and sleep-maintenance insomnia. It has a longer half-life than other agents in the same category and helps decrease sleep-onset latency and wake time after sleep onset and increases sleep efficiency. Higher doses of eszopiclone are effective for sleep maintenance, whereas lower doses are used to treat patients who have difficulty falling asleep. Adverse reactions include bitter taste, dizziness, dry mouth, and somnolence.

The melatonin-receptor agonist ramelteon (Rozerem) reduces sleep-onset latency and increases time of sleep in adults with chronic insomnia. Ramelteon can be safely used for long-term treatment of insomnia without the risk of abuse or dependence. Patients who use ramelteon don't usually experience rebound or withdrawal symptoms. It also has anxiolytic and muscle-relaxant properties. Common adverse reactions include headache, fatigue, somnolence, dizziness, and nausea.

Trazodone (Desyrel), an antidepressant, is one of the two most commonly prescribed agents for the treatment of insomnia (the other being zolpidem). It's a weak selective inhibitor of serotonin reuptake and acts by antagonism of the central alpha1-adrenergic and histamine1 receptors. A decline in efficacy with long-term use along with the possibility of rebound insomnia has been seen when trazodone therapy is stopped. Some common adverse reactions include dry mouth, dizziness, drowsiness, nausea, vomiting, constipation, headache, blurred vision, hypotension, next-day drowsiness, and difficulty wakening. More serious adverse reactions include priapism and cardiac effects such as syncope, ischemic attacks, and arrhythmias.

Natural supplements that are available over the counter are often used to treat insomnia. They include melatonin and valerian. Melatonin is a hormone that regulates sleep and wake cycles. It's available as a supplement that improves sleep-onset latency and sleep efficacy. Melatonin is considered safe for short-term use; common adverse reactions include dizziness, drowsiness, headache, fatigue, and irritability. Other adverse reactions include mood changes, hypotension, mild GI effects, and increased intraocular pressure. Patients with vascular disease and those taking immunosuppressive therapy shouldn't take melatonin.

Valerian is a perennial plant that's native to both Asia and Europe. Even though this supplement is seen as generally safe, there are some adverse reactions associated with its use, including dizziness, headache, excitability, ataxia, and hangover effect.

Restful sleep
If your patient is using sleep aids, educate him on the prescribed use of the medication he's taking, how and when to take it, and to report any adverse reactions to his healthcare provider.

Insomnia is a common ailment that affects more than half the population of the United States, so you're sure to see many patients with this problem. Knowing what type of insomnia they have can help you determine the best course of action and the best medication to use to help them get the restful sleep they need.

Criteria for diagnosing insomnia
Patient should have at least one of the following:

  • difficulty initiating or maintaining sleep
  • sleep that's poor in quality
  • trouble sleeping despite adequate opportunity and circumstances for sleep
  • waking up too early.

Patient should have at least one of the following types of daytime impairment related to sleep difficulty:

  • attention, concentration, or memory impairment
  • concerns or worries about sleep
  • daytime sleepiness
  • errors or accidents at work or while driving
  • fatigue or malaise
  • gastrointestinal symptoms
  • lack of motivation
  • mood disturbance or irritability
  • social or vocational dysfunction or poor school performance
  • tension headaches.

Source: American Academy of Sleep Medicine. International Classification of Sleep Disorders: Diagnostic and Coding Manual. 2nd ed. Westchester, IL: American Academy of Sleep Medicine; 2005.


Selected references
Budur K, Rodriguez C, Foldvary-Schaefer N. Advances in treating insomnia. Cleve Clin J Med. 2007;74(4):251–266.
Calamaro C. Sleeping through the night: are extended release formulations the answer? Am Acad Nurse Pract. 2008;20(2):69–75.
Morin AK, Jarvis CI, Lynch AM. Therapeutic options for sleep-maintenance and sleep-onset insomnia. Pharmacotherapy. 2007;27(1):251–266.
Ramakrishnan K, Scheid DC. Treatment options for insomnia. Am Fam Physician. 2007;76(4):517–526.
Roth T. The nature of insomnia. CNS Spectrums. 2007;12(7 suppl 10):3–5.
Tariq SH, Pullsetty S. Pharmacotherapy for insomnia. Clin Geriatr Med. 2008;24(1):93–105.
Winkelman J, Pies R. Current patterns and future directions in the treatment of insomnia. Ann Clin Psychiat. 2005;17:31–40.
Zammit GK. The prevalence, morbidities, and treatments of insomnia. CNS Neurol Disord Drug Target. 2007;6(1):3–16.

Source: LPN2009. May/June 2009.

     
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