Insomnia

This article is about the sleeping disorder. For other uses, see Insomnia (disambiguation).
Insomnia
Classification and external resources
ICD-10 F51.0, G47.0
ICD-9 307.42, 307.41, 327.0, 780.51, 780.52
DiseasesDB 26877
MedlinePlus 000805
eMedicine med/2698
Patient UK Insomnia
MeSH D007319

Insomnia, or sleeplessness, is a sleep disorder in which there is an inability to fall asleep or to stay asleep as long as desired.[1][2] While the term is sometimes used to describe a disorder demonstrated by polysomnographic or actigraphic evidence of disturbed sleep, this sleep disorder is often practically defined as a positive response to either of two questions: "Do you experience difficulty sleeping?" or "Do you have difficulty falling or staying asleep?"[2]

Insomnia is most often thought of as both a medical sign and a symptom[2][3] that can accompany several sleep, medical, and psychiatric disorders characterized by a persistent difficulty falling asleep and/or staying asleep or sleep of poor quality. Insomnia is typically followed by functional impairment while awake. Insomnia can occur at any age, but it is particularly common in the elderly.[4] Insomnia can be short term (up to three weeks) or long term (above 3–4 weeks); it can lead to memory problems, depression, irritability and an increased risk of heart disease and automobile related accidents.[5]

Those who are having trouble sleeping sometimes turn to sleeping pills, which may help, but also may lead to substance dependency or addiction if used regularly for an extended period.[6]

Insomnia can be grouped into primary and secondary, or comorbid, insomnia.[7][8][9] Primary insomnia is a sleep disorder not attributable to a medical, psychiatric, or environmental cause.[10] It is described as a complaint of prolonged sleep onset latency, disturbance of sleep maintenance, or the experience of non-refreshing sleep.[11] A complete diagnosis will differentiate between free-standing primary insomnia, insomnia as secondary to another condition, and primary insomnia co-morbid with one or more conditions.

Classification

DSM-5 criteria for insomnia

The DSM-5 criteria for insomnia include the following:[12]

Predominant complaint of dissatisfaction with sleep quantity or quality, associated with one (or more) of the following symptoms:

In addition,

note: The DSM-5 criteria for insomnia is intended for use by general mental health and medical clinicians (those caring for adult, geriatric, and pediatric patients).

Types of insomnia

Insomnia can be classified as transient, acute, or chronic.

  1. Transient insomnia lasts for less than a week. It can be caused by another disorder, by changes in the sleep environment, by the timing of sleep, severe depression, or by stress. Its consequences – sleepiness and impaired psychomotor performance – are similar to those of sleep deprivation.[13]
  2. Acute insomnia is the inability to consistently sleep well for a period of less than a month. Insomnia is present when there is difficulty initiating or maintaining sleep or when the sleep that is obtained is non-refreshing or of poor quality. These problems occur despite adequate opportunity and circumstances for sleep and they must result in problems with daytime function.[14] Acute insomnia is also known as short term insomnia or stress related insomnia.[15]
  3. Chronic insomnia lasts for longer than a month. It can be caused by another disorder, or it can be a primary disorder. People with high levels of stress hormones or shifts in the levels of cytokines are more likely than others to have chronic insomnia.[16] Its effects can vary according to its causes. They might include muscular fatigue, hallucinations, and/or mental fatigue. Chronic insomnia can cause double vision.[13]

Patterns of insomnia

Symptoms of insomnia:[17]
  • difficulty falling asleep, including difficulty finding a comfortable sleeping position
  • waking during the night and being unable to return to sleep
  • feeling unrefreshed upon waking
  • daytime sleepiness, irritability or anxiety

Sleep-onset insomnia is difficulty falling asleep at the beginning of the night, often a symptom of anxiety disorders. Delayed sleep phase disorder can be misdiagnosed as insomnia, as sleep onset is delayed to much later than normal while awakening spills over into daylight hours.[18]

It is common for patients who have difficulty falling asleep to also have nocturnal awakenings with difficulty returning to sleep. Two thirds of these patients wake up in middle of the night, with more than half having trouble falling back to sleep after a middle of the night awakening.[19]

Early morning awakening is an awakening occurring earlier (more than 30 minutes) than desired with an inability to go back to sleep, and before total sleep time reaches 6.5 hours. Early morning awakening is often a characteristic of depression.[20]

Poor sleep quality

Poor sleep quality can occur as a result of, for example, restless legs, sleep apnea or major depression. Poor sleep quality is caused by the individual not reaching stage 3 or delta sleep which has restorative properties.

Major depression leads to alterations in the function of the hypothalamic-pituitary-adrenal axis, causing excessive release of cortisol which can lead to poor sleep quality.

Nocturnal polyuria, excessive nighttime urination, can be very disturbing to sleep.[21]

Subjective insomnia

Some cases of insomnia are not really insomnia in the traditional sense. People experiencing sleep state misperception often sleep for normal durations, yet severely overestimate the time taken to fall asleep. They may believe they slept for only four hours while they, in fact, slept a full eight hours.

Causes and comorbidity

Potential complications of insomnia.[22]

Symptoms of insomnia can be caused by or be co-morbid with:

Sleep studies using polysomnography have suggested that people who have sleep disruption have elevated nighttime levels of circulating cortisol and adrenocorticotropic hormone They also have an elevated metabolic rate, which does not occur in people who do not have insomnia but whose sleep is intentionally disrupted during a sleep study. Studies of brain metabolism using positron emission tomography (PET) scans indicate that people with insomnia have higher metabolic rates by night and by day. The question remains whether these changes are the causes or consequences of long-term insomnia.[33]

Steroid hormones and insomnia

Studies have been conducted with steroid hormones and insomnia. Changes in levels of cortisol, progesterone in the female cycle, or estrogen during menopause are correlated with increased occurrences of insomnia. Those with differing levels of cortisol often have long-term insomnia, where estrogen is onset insomnia catalyzed by menopause, and progesterone is temporary insomnia within the monthly female cycle.

Cortisol

Cortisol is typically thought of as the stress hormone in humans, but it is also the awakening hormone.[36] Analyzing saliva samples taken in the morning has shown that patients with insomnia wake up with significantly lower cortisol levels when compared to a control group with regular sleeping patterns.[37] Further studies have revealed that those with lower levels of cortisol upon awakening also have poorer memory consolidation in comparison to those with normal levels of cortisol.[38] Studies support that larger amounts of cortisol released in the evening occurs in primary insomnia. In this case, drugs related to calming mood disorders or anxiety, such as antidepressants, would regulate the cortisol levels and help prevent insomnia.[39]

Estrogen

Many postmenopausal women have reported changes in sleep patterns since entering menopause that reflect symptoms of insomnia. This could occur because of the lower levels of estrogen. Lower estrogen levels can cause hot flashes, change in stress reactions, or overall change in the sleep cycle, which all could contribute to insomnia. Estrogen treatment as well as estrogen-progesterone combination supplements as a hormone replacement therapy can help regulate menopausal women’s sleep cycle again.[40]

Progesterone

Low levels of progesterone throughout the female menstruation cycle, but primarily near the end of the luteal phase, have also been known to correlate with insomnia as well as aggressive behavior, irritability, and depressed mood in women.[41] Around 67% of women have problems with insomnia right before or during their menstrual cycle.[42] Lower levels of progesterone can, like estrogen, correlate with insomnia in menopausal women.[40]

A common misperception is that the amount of sleep required decreases as a person ages. The ability to sleep for long periods, rather than the need for sleep, appears to be lost as people get older. Some elderly insomniacs toss and turn in bed and occasionally fall off the bed at night, diminishing the amount of sleep they receive.[43]

Risk factors

Insomnia affects people of all age groups but people in the following groups have a higher chance of acquiring insomnia.

Diagnosis

In medicine, insomnia is widely measured using the Athens insomnia scale.[44] It is measured using eight different parameters related to sleep, finally it is represented as an overall scale which assess an individual's sleep pattern

A qualified sleep specialist should be consulted in the diagnosis of any sleep disorder so the appropriate measures can be taken. Past medical history and a physical examination need to be done to eliminate other conditions that could be the cause of the insomnia. After all other conditions are ruled out a comprehensive sleep history should be taken. The sleep history should include sleep habits, medications (prescription and non-prescription), alcohol consumption, nicotine and caffeine intake, co-morbid illnesses, and sleep environment.[45] A sleep diary can be used to keep track of the individual's sleep patterns. The diary should include time to bed, total sleep time, time to sleep onset, number of awakenings, use of medications, time of awakening and subjective feelings in the morning.[45]

Workers who complain of insomnia should not routinely have polysomnography to screen for sleep disorders.[46] This test may be indicated for patients with symptoms in addition to insomnia, including sleep apnea, obesity, a risky neck diameter, or risky fullness of the flesh in the oropharynx.[46] Usually, the test is not needed to make a diagnosis, and insomnia especially for working people can often be treated by changing a job schedule to make time for sufficient sleep and by improving sleep hygiene.[46]

Some patients may need to do a sleep study to determine if insomnia is present. The sleep study will involve the assessment tools of a polysomnogram and the multiple sleep latency test and will be conducted in a sleep center or a designated hotel. Specialists in sleep medicine are qualified to diagnose the many different sleep disorders. Patients with various disorders, including delayed sleep phase syndrome, are often mis-diagnosed with primary insomnia. When a person has trouble getting to sleep, but has a normal sleep pattern once asleep, a delayed circadian rhythm is the likely cause.

In many cases, insomnia is co-morbid with another disease, side-effects from medications, or a psychological problem. Approximately half of all diagnosed insomnia is related to psychiatric disorders.[47] In depression in many cases "insomnia should be regarded as a co-morbid condition, rather than as a secondary one;" insomnia typically predates psychiatric symptoms.[47] "In fact, it is possible that insomnia represents a significant risk for the development of a subsequent psychiatric disorder."[2]

Knowledge of causation is not necessary for a diagnosis.[47]

Treatment

It is important to identify or rule out medical and psychological causes before deciding on the treatment for insomnia.[48] Cognitive behavioral therapy (CBT) "has been found to be as effective as prescription medications are for short-term treatment of chronic insomnia. Moreover, there are indications that the beneficial effects of CBT, in contrast to those produced by medications, may last well beyond the termination of active treatment."[49] Pharmacological treatments have been used mainly to reduce symptoms in acute insomnia; their role in the management of chronic insomnia remains unclear.[7] Several different types of medications are also effective for treating insomnia. However, many doctors do not recommend relying on prescription sleeping pills for long-term use. It is also important to identify and treat other medical conditions that may be contributing to insomnia, such as depression, breathing problems, and chronic pain.[50]

Non-pharmacological

Non-pharmacological strategies have comparable efficacy to hypnotic medication for insomnia and they may have longer lasting effects. Hypnotic medication is only recommended for short-term use because dependence with rebound withdrawal effects upon discontinuation or tolerance can develop.[51]

Non pharmacological strategies provide long lasting improvements to insomnia and are recommended as a first line and long term strategy of management. The strategies include attention to sleep hygiene, stimulus control, behavioral interventions, sleep-restriction therapy, paradoxical intention, patient education and relaxation therapy.[52] Reducing the temperature of blood flowing to the brain slows the brain's metabolic rate thereby reducing insomnia.[53] Some examples are keeping a journal, restricting the time spending awake in bed, practicing relaxation techniques, and maintaining a regular sleep schedule and a wake-up time.[50] Behavioral therapy can assist a patient in developing new sleep behaviors to improve sleep quality and consolidation. Behavioral therapy may include, learning healthy sleep habits to promote sleep relaxation, undergoing light therapy to help with worry-reduction strategies and regulating the circadian clock.[50]

EEG biofeedback has demonstrated effectiveness in the treatment of insomnia with improvements in duration as well as quality of sleep.[54]

Sleep hygiene is a common term for all of the behaviors which relate to the promotion of good sleep. These behaviors are used as the basis of sleep interventions and are the primary focus of sleep education programs.[55] Behaviors include the use of caffeine, nicotine and alcohol consumption, maximizing the regularity and efficiency of sleep episodes, minimizing medication usage and daytime napping, the promotion of regular exercise, and the facilitation of a positive sleep environment.[55] Exercise can be helpful when establishing a routine for sleep but should not be done close to the time that you are planning on going to sleep. The creation of a positive sleep environment may also be helpful in reducing the symptoms of insomnia. In order to create a positive sleep environment one should remove objects that can cause worry or distressful thoughts from view.

Stimulus control therapy is a treatment for patients who have conditioned themselves to associate the bed, or sleep in general, with a negative response. As stimulus control therapy involves taking steps to control the sleep environment, it is sometimes referred interchangeably with the concept of sleep hygiene. Examples of such environmental modifications include using the bed for sleep or sex only, not for activities such as reading or watching television; waking up at the same time every morning, including on weekends; going to bed only when sleepy and when there is a high likelihood that sleep will occur; leaving the bed and beginning an activity in another location if sleep does not result in a reasonably brief period of time after getting into bed (commonly ~20 min); reducing the subjective effort and energy expended trying to fall asleep; avoiding exposure to bright light during nighttime hours, and eliminating daytime naps.[56]

A component of stimulus control therapy is sleep restriction, a technique that aims to match the time spent in bed with actual time spent asleep. This technique involves maintaining a strict sleep-wake schedule, sleeping only at certain times of the day and for specific amounts of time to induce mild sleep deprivation. Complete treatment usually lasts up to 3 weeks and involves making oneself sleep for only a minimum amount of time that they are actually capable of on average, and then, if capable (i.e. when sleep efficiency improves), slowly increasing this amount (~15 min) by going to bed earlier as the body attempts to reset its internal sleep clock. Bright light therapy, which is often used to help early morning wakers reset their natural sleep cycle, can also be used with sleep restriction therapy to reinforce a new wake schedule. Although applying this technique with consistency is difficult, it can have a positive effect on insomnia in motivated patients.

Paradoxical intention is a cognitive reframing technique where the insomniac, instead of attempting to fall asleep at night, makes every effort to stay awake (i.e. essentially stops trying to fall asleep). One theory that may explain the effectiveness of this method is that by not voluntarily making oneself go to sleep, it relieves the performance anxiety that arises from the need or requirement to fall asleep, which is meant to be a passive act. This technique has been shown to reduce sleep effort and performance anxiety and also lower subjective assessment of sleep-onset latency and overestimation of the sleep deficit (a quality found in many insomniacs).[57]

Meditation has been recommended for the treatment of insomnia. The meditation teacher Siddhārtha Gautama, 'The Buddha', is recorded as having recommended the practice of 'loving-kindness' meditation, or mettā bhāvanā as a way to produce relaxation and thereby, sound sleep – putting it first in a list of the benefits of that meditation.[58] More recently, studies have concluded that: a mindfulness practice reduced mental and bodily restlessness before sleep and the subjective symptoms of insomnia;[59] and that mindfulness-based cognitive behavioural therapy reduced restlessness, sleep effort and dysfunctional sleep-related thoughts[60] including worry.[61]

Cognitive behavioral therapy

There is some evidence that cognitive behavioural therapy for insomnia is superior in the long-term to benzodiazepines and the nonbenzodiazepines in the treatment and management of insomnia.[62] In this therapy, patients are taught improved sleep habits and relieved of counter-productive assumptions about sleep. Common misconceptions and expectations that can be modified include: (1) unrealistic sleep expectations (e.g., I need to have 8 hours of sleep each night), (2) misconceptions about insomnia causes (e.g., I have a chemical imbalance causing my insomnia), (3) amplifying the consequences of insomnia (e.g., I cannot do anything after a bad night's sleep), and (4) performance anxiety after trying for so long to have a good night's sleep by controlling the sleep process. Numerous studies have reported positive outcomes of combining cognitive behavioral therapy for insomnia treatment with treatments such as stimulus control and the relaxation therapies. Hypnotic medications are equally effective in the short-term treatment of insomnia but their effects wear off over time due to tolerance. The effects of CBT-I have sustained and lasting effects on treating insomnia long after therapy has been discontinued.[63][64] The addition of hypnotic medications with CBT-I adds no benefit in insomnia. The long lasting benefits of a course of CBT-I shows superiority over pharmacological hypnotic drugs. Even in the short term when compared to short-term hypnotic medication such as zolpidem (Ambien), CBT-I still shows significant superiority. Thus CBT-I is recommended as a first line treatment for insomnia.[65] Metacognition is also a recent trend in approach to behaviour therapy of insomnia.[66]

Prevention

Insomnia can be short-term or long-term. Prevention of the sleep disorder may include maintaining a consistent sleeping schedule, such as waking up and sleeping at the same times every day. Also, one should avoid caffeinated drinks during the 8 hours before sleeping time. While exercise is essential and can aid the process of sleeping, it is important to not exercise right before bedtime, therefore creating a calm environment. Lastly, one's bed should only be for sleep and sex. These are some of the points included in sleep hygiene. Going to sleep and waking up at the same time every day can create a steady pattern, which may help against insomnia.[1]

Internet interventions

Despite the therapeutic effectiveness and proven success of CBT, treatment availability is significantly limited by a lack of trained clinicians, poor geographical distribution of knowledgeable professionals, and expense.[67] One way to potentially overcome these barriers is to use the Internet to deliver treatment, making this effective intervention more accessible and less costly. The Internet has already become a critical source of health-care and medical information.[68] Although the vast majority of health websites provide general information,[68][69] there is growing research literature on the development and evaluation of Internet interventions.[70][71]

These online programs are typically behaviorally-based treatments that have been operationalized and transformed for delivery via the Internet. They are usually highly structured; automated or human supported; based on effective face-to-face treatment; personalized to the user; interactive; enhanced by graphics, animations, audio, and possibly video; and tailored to provide follow-up and feedback.[71]

A number of Internet interventions for insomnia have been developed[72] and a few of them have been evaluated as part of scientific research trials.

A paper published in 2012 reviewed the related literature[73] and found good evidence for the use of Internet interventions for insomnia.

Medications

Many insomniacs rely on sleeping tablets and other sedatives to get rest. In some places medications are prescribed to over 95% of insomniac cases.[74] The percentage of adults using a prescription sleep aid increases with age. During 2005–2010, about 4% of U.S. adults aged 20 and over reported that they took prescription sleep aids in the past 30 days. Prevalence of use was lowest among the youngest age group (those aged 20–39) at about 2%, increased to 6% among those aged 50–59, and reached 7% among those aged 80 and over. More adult women (5.0%) reported using prescription sleep aids than adult men (3.1%). Non-Hispanic white adults reported higher use of sleep aids (4.7%) than non-Hispanic black (2.5%) and Mexican-American (2.0%) adults. No difference was shown between non-Hispanic black adults and Mexican-American adults in use of prescription sleep aids.[75] As an alternative to taking prescription drugs, some evidence shows that an average person seeking short-term help may find relief from taking over-the-counter antihistamines such as diphenhydramine or doxylamine.[76] Certain classes of sedatives such as benzodiazepines and newer nonbenzodiazepine drugs can also cause physical dependence, which manifests in withdrawal symptoms if the drug is not carefully tapered down. The benzodiazepine and nonbenzodiazepine hypnotic medications also have a number of side-effects such as day time fatigue, motor vehicle crashes, cognitive impairments and falls and fractures. Elderly people are more sensitive to these side-effects.[77] The non-benzodiazepines zolpidem and zaleplon have not adequately demonstrated effectiveness in sleep maintenance. Some benzodiazepines have demonstrated effectiveness in sleep maintenance in the short term but in the longer term are associated with tolerance and dependence. Drugs that may prove more effective and safer than existing drugs for insomnia is an area of active research.[78]

Benzodiazepines and nonbenzodiazepines have similar efficacy that is not significantly more than for antidepressants.[79] Benzodiazepines did not have a significant tendency for more adverse drug reactions.[79] Chronic users of hypnotic medications for insomnia do not have better sleep than chronic insomniacs not taking medications. In fact, chronic users of hypnotic medications have more regular nighttime awakenings than insomniacs not taking hypnotic medications.[80] A further review of the literature regarding benzodiazepine hypnotic as well as the nonbenzodiazepines concluded that these drugs cause an unjustifiable risk to the individual and to public health and lack evidence of long-term effectiveness. The risks include dependence, accidents, and other adverse effects. Gradual discontinuation of hypnotics in long-term users leads to improved health without worsening of sleep. It is preferred that hypnotics be prescribed for only a few days at the lowest effective dose and avoided altogether wherever possible in the elderly.[81]

Antihistamines

The antihistamine diphenhydramine is widely used in nonprescription sleep aids such as Benadryl. The antihistamine doxylamine is used in nonprescription sleep aids such as Unisom (USA) and Unisom 2 (Canada). In some countries, including Australia, it is marketed under the names Restavit and Dozile. It is the most effective over-the-counter sedative currently available in the United States, and is more sedating than some prescription hypnotics.[82]

While the two drugs mentioned above are available over the counter in most countries, the effectiveness of these agents may decrease over time, and the incidence of next-day sedation is higher than for most of the newer prescription drugs. Anticholinergic side-effects may also be a draw back of these particular drugs. While addiction does not seem to be an issue with this class of drugs, they can induce dependence and rebound effects upon abrupt cessation of use.

Benzodiazepines

Normison (temazepam) is a benzodiazepine commonly prescribed for insomnia and other sleep disorders.[83]

The most commonly used class of hypnotics prescribed for insomnia are the benzodiazepines. Benzodiazepines all bind unselectively to the GABAA receptor.[79] But certain benzodiazepines (hypnotic benzodiazepines) have significantly higher activity at the α1 subunit of the GABAA receptor compared to other benzodiazepines (for example, triazolam and temazepam have significantly higher activity at the α1 subunit compared to alprazolam and diazepam, making them superior sedative-hypnotics – alprazolam and diazepam in turn have higher activity at the α2 subunit compared to triazolam and temazepam, making them superior anxiolytic agents). Modulation of the α1 subunit is associated with sedation, motor-impairment, respiratory depression, amnesia, ataxia, and reinforcing behavior (drug-seeking behavior). Modulation of the α2 subunit is associated with anxiolytic activity and disinhibition. For this reason, certain benzodiazepines are better suited to treat insomnia than others. Hypnotic benzodiazepines include drugs such as temazepam, clonazepam, lorazepam, oxazepam, diazepam, flunitrazepam, triazolam, flurazepam, midazolam, nitrazepam, and quazepam. These drugs can lead to tolerance, physical dependence, and the benzodiazepine withdrawal syndrome upon discontinuation, especially after consistent usage over long periods of time. Benzodiazepines, while inducing unconsciousness, actually worsen sleep as they promote light sleep while decreasing time spent in deep sleep.[84] A further problem is, with regular use of short-acting sleep aids for insomnia, daytime rebound anxiety can emerge.[85] Benzodiazepines can help to initiate sleep and increase sleep time, but they also decrease deep sleep and increase light sleep. Although there is little evidence for benefit of benzodiazepines in insomnia and evidence of major harm, prescriptions have continued to increase.[86] There is a general awareness that long-term use of benzodiazepines for insomnia in most people is inappropriate and that a gradual withdrawal is usually beneficial due to the adverse effects associated with the long-term use of benzodiazepines and is recommended whenever possible.[87][88]

Non-benzodiazepines

Nonbenzodiazepine sedative-hypnotic drugs, such as zolpidem (Ambien), zaleplon, zopiclone (Imovane), and eszopiclone (Lunesta), are a class hypnotic medications indicated for mild to moderate insomnia. Their effectiveness at improving time to sleeping is slight.[89]

Orexin antagonists

Suvorexant is a recently FDA approved treatment for insomnia, characterized by difficulties with sleep onset and/or sleep maintenance.[90] It exerts its therapeutic effect in insomnia through antagonism of orexin receptors. The orexin neuropeptide signaling system is a central promoter of wakefulness. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors orexin receptor type 1 and orexin receptor type 2 is thought to suppress wake drive.[90] Two other dual orexin antagonists currently in clinical trials are Filorexant and SB-649,868.

Antidepressants

Some antidepressants such as amitriptyline, doxepin, mirtazapine, and trazodone can have a sedative effect, and are prescribed to treat insomnia.[91] Amitriptyline and doxepin both have antihistaminergic, anticholinergic, and antiadrenergic properties, which contribute to their side effect profile, while mirtazapine's side effects are primarily antihistaminergic, and trazadone's side-effects are primarily antiadrenergic. Some also alter sleep architecture. As with benzodiazepines, the use of antidepressants in the treatment of insomnia can lead to withdrawal effects; withdrawal may induce rebound insomnia.

Mirtazapine is known to decrease sleep latency, promoting sleep efficiency and increasing the total amount of sleeping time in people with both depression and insomnia.[92][93]

Agomelatine a novel melatonergic antidepressant with sleep-improving qualities that does not cause daytime drowsiness,[94] is licensed for marketing in the European Union [95] and TGA Australia.[96] After trials in the United States its development for use there was discontinued in October 2011[97] by Novartis, who had bought the rights to market it there from the European pharmaceutical company Servier.[98]

Melatonin

Melatonin is a hormone synthesized by the pineal gland, secreted through the bloodstream in the dark or commonly at nighttime, in order to control the sleep cycle.[99] It is available in some countries labeled "dietary supplement".

Evidence for ramelteon, a melatonin receptor agonist approved by the Food and Drug Administration, looks promising.[100] It and tasimelteon increase sleep time due to a melatonin rhythm shift with no apparent negative effects on the next day.[99][101] Most melatonin drugs have not been tested for longitudinal side effects.[101]

Studies have also shown that children who are on the Autism spectrum or have learning disabilities, Attention-Deficit Hyperactivity Disorder (ADHD) or related neurological diseases can benefit from the use of melatonin. This is because they often have trouble sleeping due to their disorders. For example, children with ADHD tend to have trouble falling asleep because of their hyperactivity and, as a result, tend to be tired during most of the day. Children who have ADHD then, as well as the other disorders mentioned, may be given melatonin before bedtime in order to help them sleep.[102]

Alcohol

Alcohol is often used as a form of self-treatment of insomnia to induce sleep. However, alcohol use to induce sleep can be a cause of insomnia. Long-term use of alcohol is associated with a decrease in NREM stage 3 and 4 sleep as well as suppression of REM sleep and REM sleep fragmentation. Frequent moving between sleep stages occurs, with awakenings due to headaches, the need to urinate, dehydration, and excessive sweating. Glutamine rebound also plays a role as when someone is drinking; alcohol inhibits glutamine, one of the body's natural stimulants. When the person stops drinking, the body tries to make up for lost time by producing more glutamine than it needs. The increase in glutamine levels stimulates the brain while the drinker is trying to sleep, keeping him/her from reaching the deepest levels of sleep.[103] Stopping chronic alcohol use can also lead to severe insomnia with vivid dreams. During withdrawal REM sleep is typically exaggerated as part of a rebound effect.[104]

Opioids

Opioid medications such as hydrocodone, oxycodone, and morphine are used for insomnia that is associated with pain due to their analgesic properties and hypnotic effects. Opioids can fragment sleep and decrease REM and stage 2 sleep. By producing analgesia and sedation, opioids may be appropriate in carefully selected patients with pain-associated insomnia.[28] However, dependence on opioids can lead to suffering from long time disturbance in sleep.[105]

Antipsychotics

The use of antipsychotics for insomnia, while common, is not recommended as the evidence does not demonstrate a benefit and the risk of adverse effects is significant.[106][107] Concerns regarding side effects is greater in the elderly.[108]

Alternative medicine

Some insomniacs use herbs such as valerian, chamomile, lavender, cannabis, hops, Withania somnifera, and passion-flower. L-Arginine L-aspartate, S-adenosyl-L-homocysteine, and delta sleep-inducing peptide (DSIP) may be also helpful in alleviating insomnia.[109]

Epidemiology

Disability-adjusted life year for insomnia per 100,000 inhabitants in 2002.
  no data
  less than 25
  25–30.25
  30.25–36
  36–41.5
  41.5–47
  47–52.5
  52.5–58
  58–63.5
  63.5–69
  69–74.5
  74.5–80
  more than 80

A survey of 1.1 million residents in the United States found that those that reported sleeping about 7 hours per night had the lowest rates of mortality, whereas those that slept for fewer than 6 hours or more than 8 hours had higher mortality rates. Getting 8.5 or more hours of sleep per night increased the mortality rate by 15%. Severe insomnia – sleeping less than 3.5 hours in women and 4.5 hours in men – also led to a 15% increase in mortality. However, most of the increase in mortality from severe insomnia was discounted after controlling for co-morbid disorders. After controlling for sleep duration and insomnia, use of sleeping pills was also found to be associated with an increased mortality rate.[110]

The lowest mortality was seen in individuals who slept between six and a half and seven and a half hours per night. Even sleeping only 4.5 hours per night is associated with very little increase in mortality. Thus, mild to moderate insomnia for most people is associated with increased longevity and severe insomnia is associated only with a very small effect on mortality.[110]

As long as a patient refrains from using sleeping pills, there is little to no increase in mortality associated with insomnia, but there does appear to be an increase in longevity. This is reassuring for patients with insomnia in that, despite the sometimes-unpleasantness of insomnia, insomnia itself appears to be associated with increased longevity.[110] It is unclear why sleeping longer than 7.5 hours is associated with excess mortality.[110]

Insomnia is 40% more common in women than in men.[111]

Prevalence

The National Sleep Foundation's 2002 Sleep in America poll showed that 58% of adults in the U.S. experienced symptoms of insomnia a few nights a week or more.[112] Although insomnia was the most common sleep problem among about one half of older adults (48%), they were less likely to experience frequent symptoms of insomnia than their younger counterparts (45% vs. 62%), and their symptoms were more likely to be associated with medical conditions, according to the poll of adults between the ages of 55 and 84.[112]

As explained by Thomas Roth,[2] estimates of the prevalence of insomnia depend on the criteria used as well as the population studied. About 30% of adults report at least one of the symptoms of insomnia. When daytime impairment is added as a criterion, the prevalence is about 10%. Primary insomnia persisting for at least one month yields estimates of 6%.

Society

The topic of insomnia is discussed in many cultural contexts.[113][114]

See also

References

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