|
|
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.
|