Insomnia

Insomnia is difficulty getting to sleep or staying asleep, or having nonrefreshing sleep for at least 1 month.


Insomnia may be a comorbid condition to many diseases including cancer, HIV, arthritic conditions, heart disease, diabetes, and obesity. It is also prevalent in patients with psychiatric disorders including anxiety, depression, panic disorder and schizophrenia.

Causes, incidence, and risk factors

Primary insomnia refers to insomnia that is not caused by any known physical or mental condition.

Insomnia is caused by many different things. The most common causes of insomnia are:

• Alcohol
• Anxiety
• Coffee
• Stress

Secondary insomnia is caused by a medical condition. Depression is a very common cause of secondary insomnia. Often, insomnia is the symptom that causes people with depression to seek medical help.

Symptoms

• Difficulty falling asleep on most nights
• Feeling tired during the day or falling asleep during the day
• Not feeling refreshed when you wake up
• Waking up several times during sleep

People who have primary insomnia tend to keep thinking about getting enough sleep. The more they try to sleep, the greater their sense of frustration and distress, and the more difficult sleep becomes.

Signs and tests

Your health care provider will do a physical exam and ask you questions about your current medications, drug use, and medical history. Usually, these are the only methods needed to diagnose insomnia.

Polysomnography, an overnight sleep study, can help rule out other types of sleep disorders (such as sleep apnea).

Drugs that can cause insomnia include amphetamines (eg,dexamphetamine), quinolone antibiotics (eg, ciprofloxacin), antidepressants (eg, paroxetine), sympathomimetics (eg, pseudoephedrine), bronchodilators (eg, theophylline), and pain relievers that may contain caffeine.

Medications:

The management of insomnia depends on the type of insomnia, persistence of symptoms, and concurrent medical conditions. An ideal hypnotic would have a quick onset of action, a sufficiently sustained duration of action, and would leave no residual effects the following morning.

Long-term use of hypnotics may lead to tolerance, reduced efficacy, and dependence. Avoid abrupt cessation; a gradual dosage-tapering schedule should be employed after extended therapy to prevent rebound insomnia.

Hypnotics should not be given to patients with sleep apnea due to reduced upper airway muscle tone and decreased arousal response to hypoxia.

ANTIHISTAMINES:

 First generation antihistamines (eg, diphenhydramine) reversibly depress CNS activity and produce their hypnotic effect by competitive inhibition of histamine-1 and muscarinic receptors. Antihistamines should only be used for the short-term management of occasional insomnia in conjunction with good sleep hygiene. Side effects include daytime sedation and anticholinergic effects. Elderly patients are more likely to experience adverse anticholinergic effects.

BARBITURATES: 

Barbiturates cause a nonselective depressant effect throughout the CNS with actions ranging from mild sedation to anesthesia. Sedative-hypnotic effects of barbiturates are due to its activity on gamma-aminobutyric acid (GABA). Barbiturates potentiate GABA activity by enhancing the binding of GABA to GABA_Areceptors and by prolonging the opening of chloride channels to augment GABA-induced chloride currents.

Short-acting barbiturates (eg, pentobarbital) are preferred over longer-acting products (eg, phenobarbital) for the management of insomnia. However, barbiturates are not often used as hypnotics due to safety considerations such as rapid development of tolerance, fatalities by overdose, increased potential for dependence and abuse, withdrawal symptoms, and drug interactions. 

BENZODIAZEPINES (eg, temazepam): 

Benzodiazepines exert their hypnotic effects through enhancement of the GABA-benzodiazepine receptor complex. GABA is a major inhibitory neurotransmitter in the CNS that acts on receptor subtypes GABA_A, the receptor involved in sedation, and GABA_B. Benzodiazepines nonselectively bind to GABA_A receptors, which may contribute to their hypnotic effects. Flumazenil, a benzodiazepine antagonist, can be used to counteract the sedative actions of benzodiazepines.

Long-acting benzodiazepines (eg, flurazepam) may benefit patients that also experience daytime anxiety or those receiving therapy for major depressive disorder, but are associated with next-day sedation, confusion, and a concurrent increase in falls. Short-acting benzodiazepines (eg, triazolam) are preferred for patients with sleep-onset insomnia or elderly patients, but can cause early morning awakenings, rebound next-day anxiety, and amnesia.

General Prescribing Guideline

Insomnia Level	Benzodiazepine Utilization
Mild to moderate	Alprazolam, Diazepam, Flurazepam, Lorazepam, Oxazepam Quazepam
Moderate to severe	Cinolazepam, Estazolam, Loprazolam, Lormetazepam, Midazolam, Nitrazepam
Severe to debilitating	Brotizolam, Flunitrazepam, Flutoprazepam, Nimetazepam, Temazepam, Triazolam

MELATONIN AGONISTS:

 Melatonin receptor agonists (eg, ramelteon) have a high binding affinity and selectivity for melatonin MT₁ and MT₂ receptors over the MT₃ receptors. The activity at the MT₁ and MT₂ receptors is believed to contribute to the hypnotic properties of melatonin agonists, as these receptors are thought to be involved in the maintenance of the circadian rhythm underlying the normal sleep-wake cycle.

NON-BENZODIAZEPINES (BENZODIAZEPINE-RECEPTOR AGONISTS): 

Non-benzodiazepines (eg, zolpidem,zaleplon) are chemically unrelated to benzodiazepines or barbiturates. These agents interact with the GABA-benzodiazepine receptor complex and share some pharmacologic characteristics of the benzodiazepines. It is hypothesized that these agents selectively bind to GABA_A receptors to produce their hypnotic effect. Compared to benzodiazepines, these agents have more tolerable side-effect profiles, minimal effects on sleep architecture, and are less likely to cause dependence and abuse.

Treatment

The following tips can help improve sleep. This is called sleep hygiene.

• Avoid caffeine, alcohol, or nicotine before bed.
• Don't take daytime naps.
• Eat at regular times each day (avoid large meals near bedtime).
• Exercise at least 2 hours before going to bed.
• Go to bed at the same time every night.
• Keep comfortable sleeping conditions.
• Remove the anxiety that comes with trying to sleep by reassuring yourself that you will sleep or by distracting yourself.
• Use the bed only for sleep and sex.

Do something relaxing just before bedtime (such as reading or taking a bath) so that you don't dwell on worrisome issues. Watching TV or using a computer may be stimulating to some people and interfere with their ability to fall asleep.

If you can't fall asleep within 30 minutes, get up and move to another room. Engage in a quiet activity until you feel sleepy.

One method of preventing worries from keeping you awake is to keep a journal before going to bed. List all issues that worry you. By this method, you transfer your worries from your thoughts to paper. This leaves your mind quieter and more ready to sleep.

If you follow these recommendations and still have insomnia, your doctor may prescribe medications such as benzodiazepines.