Understanding Insomnia Medications

Insomnia is the most common sleep complaint. Insomnia is defined as difficultly falling asleep or staying asleep, resulting in inadequate length of sleep and/or poor quality of sleep. Insomnia is not a disease, but a symptom associated with a variety of medical, psychiatric, or sleep disorders.

Almost everyone experiences occasional or short-term insomnia (less than three weeks). Causes of short-term insomnia are typically related to environmental factors such as too much noise or light, temperature extremes, or an uncomfortable bed. Other possible causes include stress (for example, new job or school, deadlines, or examinations) or relationship concerns or losses (for example, death of a family member or friend).

Causes of chronic insomnia (greater than three weeks) are more variable and include the following:

• Medical disorders
  
  
  • Chronic pain
    
    
  • Severe emphysema
    
    
  • Menopause
    
    
  • Chronic kidney disease (especially if undergoing dialysis)
    
    
  • Chronic fatigue syndrome
    
    
  • Fibromyalgia
  
  
• Neurologic disorders
  
  
  • Parkinson disease
    
    
  • Other movement disorders
    
    
  • Cluster headaches
    
    
• Psychiatric disorders
  
  
  • Depression
    
    
  • Schizophrenia
    
    
  • Anxiety disorders
    
    
• Drug-related insomnia
  
  
  • Stimulants (for example, caffeine)
    
    
  • Alcohol
    
    
  • Addictive substance abuse or withdrawal (for example, attempting to quit smoking)
    
    
  • Overuse of sedative-hypnotic drugs
    
    

Sleep disorders causing insomnia:

• Restless leg syndrome (RLS) is characterized by the urge to move the legs usually accompanied by an uncomfortable sensation in the legs such a crawling, burning, aching or cramping sensations. RLS often occurs at night while sitting and relaxing, and the sensation and the urge to move is often relieved by movement.  
  
  
• Periodic limb movement disorder (PLMD) occurs during sleep and involves periodic movements of the lower legs, causing brief mini-awakenings (arousals from sleep). Severe cases can cause significant sleep interruption and insomnia.
  
  
• Sleep apnea is a less common cause of insomnia. This condition is associated with loud snoring and frequent brief awakenings during the night. Many factors, including abnormal structures in the nose or throat, may cause this condition. 
  
  
• Circadian rhythm disorders (disruption of an individual’s “biological clock”) may occur when a person stays up later and sleeps later, then has difficulty returning to a more normal sleep schedule. People who work during the night (“graveyard shift”) frequently have problems with insomnia.
  
  

Primary insomnia may be diagnosed when all other disorders have been excluded. Primary insomnia is often referred to as psychophysiologic insomnia. This disorder often results from a period of stress in a person’s life. Normally, this condition resolves over time, but for some, insomnia results in ongoing tension and an inability to sleep. Bad sleep habits develop, and the person begins to worry about his or her sleep. The bad habits must be “unlearned,” and the person educated regarding good sleep hygiene practices.

Insomnia causes problems in daytime functioning. Individuals who have insomnia may report mpaired ability to concentrate, memory problems, difficulty coping with minor stressors, and decreased ability to enjoy family and social relationships. People with ongoing insomnia may become depressed. People with insomnia are twice as likely to have fatigue-related motor vehicle accidents than those without sleep problems. 

Treatment of insomnia depends on the cause. Nondrug therapy includes using relaxation therapy, controlling stimulation (for example, caffeine ingestion or evening exercise), and limiting time in bed to regular sleep hours. Medications directed toward a specific sleep-disrupting cause should also be considered.

edative-hypnotic drugs do not cure insomnia, but they may relieve symptoms. Short-term use (2-3 weeks) of sleeping pills may be warranted for chronic insomnia while other treatments or behavioral therapies are being started.

The choice of sedative-hypnotic depends on the type of sleep problem. If an individual has trouble falling asleep, a quick-acting but short-lasting drug such as zolpidem (Ambien) may be prescribed. These types of drugs are useful because they may be taken after several hours of trying to fall asleep, yet the effects do not last long enough to cause difficulty waking in the morning. Drugs that have longer-lasting actions, such as flurazepam (Dalmane), temazepam (Restoril), estazolam (ProSom), and antidepressants, are useful for individuals who wake up after initially falling asleep.

Benzodiazepine hypnotic drugs include estazolam (ProSom), flurazepam (Dalmane), temazepam (Restoril), and triazolam (Halcion).

How do benzodiazepine hypnotic drugs work? These drugs bind to benzodiazepine receptors (omega-1 and omega-2) in the brain, thereby inducing sleep.

Who should not use these medications? People with the following conditions should not use benzodiazepines:

• Allergy to benzodiazepines



• Narrow-angle glaucoma



• Untreated obstructive sleep apnea



• History of drug abuse 

Use: Take the prescribed dose 30 minutes before bedtime. Elderly individuals are prescribed smaller doses.

Drug or food interactions: Certain drugs, such as cimetidine (Tagamet), azole antifungal medications, antibiotics (for example, erythromycin [E-Mycin, Ery-Tab]), or drugs used to treat AIDS, lessen the body’s ability to eliminate benzodiazepines, thereby increasing the risk of toxicity. Some drugs, such as rifampin (Rifadin) or St. John’s Wort, may speed the metabolism (breakdown for use in the body) of sedative-hypnotics, thereby decreasing effectiveness.

Side effects: Benzodiazepines may impair coordination, balance, or mental alertness and are more likely to disrupt REM sleep, causing less restful sleep.

Nonbenzodiazepine hypnotic drugs include eszopiclone (Lunesta), zaleplon (Sonata), and zolpidem (Ambien, Ambien CR).

How do sedative hypnotic drugs work? Although these drugs are not chemically like benzodiazepines, they bind to a specific benzodiazepine receptor in the brain called omega-1, thereby inducing sleep. They may be less likely than benzodiazepine medications to disrupt natural sleep rhythm patterns (called the rapid eye movement [REM] ratio). Disruption of REM sleep may make sleep less restful. How Lunesta works is not fully understood. Lunesta is thought to promote sedation and to affect brain receptor sites that are close to gamma-aminobutyric acid (GABA).

The extended-release product (Ambien CR) consists of a coated 2-layer tablet and is useful for insomnia characterized by difficulties with sleep onset and/or sleep maintenance. The first layer releases drug content immediately to induce sleep, whereas the second layer gradually releases additional drug to provide continuous sleep.

Who should not use these medications? People with an allergy to sedative hypnotics should not take them.

Use: Take the prescribed dose 30 minutes before bedtime. Elderly individuals are prescribed smaller doses. If taking an extended-release product, such as Ambien CR, it must be swallowed whole (do not divide, chew, or crush).

Drug or food interactions: Other drugs that depress the brain, such as alcohol or barbiturates, may increase drowsiness and cause an increased risk of toxicity. Cimetidine (Tagamet) increases Sonata levels, thereby increasing the risk of toxicity. Antidepressant medication can also interact with sedative hypnotic medications. Ketoconazole (Nizoral), itraconazole (Sporanox), clarithromycin (Biaxin), nefazodone (Serzone), ritonavir (Norvir, Kaletra), and nelfinavir (Viracept) may increase blood levels of Lunesta, therefore increasing the risk for side effects. Zolpidem effect may be delayed if taken with food or shortly after a meal.

Side effects: Common side effects include drowsiness and dizziness, possibly impairing coordination, balance, and/or mental alertness. These drugs must be used with caution in individuals with a history of drug abuse or dependence. Ambien, Lunesta, and Sonata work very quickly and should only be taken just before going to bed.

Antidepressant drugs include, but are not limited to, amitriptyline (Elavil), nortriptyline (Pamelor), nefazodone (Serzone) and trazodone (Desyrel).

How do antidepressant drugs work? Some antidepressant drugs cause drowsiness as a side effect. Because this side effect may last for a long time, it can benefit an individual whose problem is awakening after initially falling asleep. Antidepressant drugs may also be used for people who have insomnia caused by depression.

Who should not use these medications? Persons taking a monamine oxidase inhibitor (MAOI, another class of antidepressant drug) should not take these medications. Additionally, anyone with the following conditions should not take antidepressants:

• Allergy to antidepressant drugs



• History of seizures



• Irregular heart rhythm



• Narrow-angle glaucoma



• Kidney disease causing retention of urine 

Use: Take the prescribed dose 30 minutes before bedtime. Elderly individuals are prescribed smaller doses.

Drug or food interactions: Do not use within 14 days of taking an MAOI. Other drugs that depress the brain, such as alcohol or barbiturates, may increase drowsiness, cause a hangover effect in the morning, and increase the risk of toxicity. Cimetidine (Tagamet) may increase blood levels of antidepressant drugs, thereby increasing the risk of toxicity.

Side effects: Common side effects include dry mouth, blurred vision, constipation, urinary retention, and increased heart rate.

Pineal gland hormones include melatonin and ramelteon (Rozerem).

How pineal gland hormones work: Melatonin is a hormone produced by the pineal gland (located in the brain) during the dark hours of the day-night cycle (circadian rhythm). Melatonin levels in the body are low during daylight hours. The pineal gland responds to darkness by increasing melatonin levels in the body. This process is thought to be integral to maintaining circadian rhythm. Ramelteon is a prescription drug that stimulates melatonin receptors. It promotes the onset of sleep and helps normalize circadian rhythm disorders. It is approved by the Food and Drug Administration for insomnia characterized by difficulty falling asleep.

Melatonin has been reported to be useful in the treatment of jet lag. Melatonin is believed to be effective when crossing 5 or more time zones and is less effective when traveling in westward direction. It is also used in the treatment of insomnia in elderly patients who are melatonin deficient and have trouble falling asleep. Melatonin has also been used for treatment of circadian rhythm sleep disorders in people who are blind and have no light perception. Melatonin is available as over-the-counter and is not approved by the FDA for sleep disorders as it is considered an alternative medicine. Caution is advised that variations in quality, purity, and quantity of active ingredient in natural pharmaceuticals make interpretation of clinical studies difficult and raises concerns about appropriate dose, drug interactions, and possible contaminants. Individual patients may or may not experience the reported benefits of melatonin. Slow-release melatonin products are reported to be less effective. 

Who should not use these medications:

• Individuals who are allergic to melatonin products or ramelteon



• Individuals with severe liver impairment (cirrhosis)

Use: Swallow prescribed dose 30 minutes before bedtime on an empty stomach.

Drug or food interactions: Drugs that inhibit metabolism of melatonin and ramelteon, such as fluvoxamine (Luvox), may increase the risk for toxicity. Rifampin increases metabolism of ramelteon, therefore decreasing its effectiveness. Melatonin has been reported to interfere with warfarin (Coumadin).

Side effects:

• Melatonin side effects may include low body temperature, headache, nightmares, and worsening of depression. Caution in individuals who have epilepsy, are taking warfarin (Coumadin), have autoimmune or endocrine disorders, or are pregnant or breastfeeding.



• Ramelteon side effects may include: Liver toxicity, dizziness, nausea, fatigue, headache, and worsening insomnia.

American Academy of Sleep Medicine
One Westbrook Corporate Center, Suite 920
Westchester, IL 60154
(708) 492-0930

American Sleep Association
614 South 8^th St, Suite 282
Philadelphia, PA 19147
(443) 593-2285
sleep@1sleep.com

National Sleep Foundation
1522 K Street, NW, Suite 500
Washington, DC 20005
(202) 347-3471
nsf@sleepfoundation.org

|Web Links|

American Insomnia Association, Medications

National Heart, Lung, and Blood Institute, Facts About Insomnia

National Center on Sleep Disorder Research

understanding insomnia medications, sleep, sleep disorders, sleep complaints, sleep habits, sleep interruption, primary insomnia, insomniacs, psychophysiologic insomnia, short-term insomnia, acute insomnia, long-term insomnia, chronic insomnia, drug-related insomnia, stress, restless leg syndrome, RLS, periodic limb movement disorder, PLMD, sleep apnea, substance abuse, circadian rhythm disorders, biological clock, impaired concentration, poor memory, depression, fatigue-related motor vehicle accidents, shift work, shift workers, sleep hygiene, relaxation therapy, sedative-hypnotic drugs, sedative-hypnotics, rapid eye movement, REM, REM sleep, parasomnias, sleep disturbance, sleepwalking, sleep walking, somnambulism

Author: Mary L Windle, Pharm D, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, .com, Inc.

Editors: Erasmo A Passaro, MD, Director, Comprehensive Epilepsy Program/Clinical Neurophysiology Lab, Bayfront Medical Center,; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, ; Stephen Berman, MD, PhD, Professor, Department of Internal Medicine, Section of Neurology, Dartmouth Medical School; Chief, White River Junction VA Neurology Service, White River Junction VA Hospital.