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Sleeping Disorders – What About You Need To Knows

Sleeping Disorders/Sleeping is an important part of your daily routine—you spend about one-third of your time doing it. Quality sleep – and getting enough of it at the right times is as essential to survival as food and water. Without sleep you can’t form or maintain the pathways in your brain that let you learn and create new memories, and it’s harder to concentrate and respond quickly.

Sleep is important to a number of brain functions, including how nerve cells (neurons) communicate with each other. In fact, your brain and body stay remarkably active while you sleep. Recent findings suggest that sleep plays a housekeeping role that removes toxins in your brain that build up while you are awake.

Everyone needs sleep, but its biological purpose remains a mystery. Sleep affects almost every type of tissue and system in the body – from the brain, heart, and lungs to metabolism, immune function, mood, and disease resistance. Research shows that a chronic lack of sleep, or getting poor quality sleep, increases the risk of disorders including high blood pressure, cardiovascular disease, diabetes, depression, and obesity.

Sleep is a complex and dynamic process that affects how you function in ways scientists are now beginning to understand. This booklet describes how your need for sleep is regulated and what happens in the brain during sleep.

Anatomy of Sleep

Several structures within the brain are involved with sleep.

The hypothalamus, a peanut-sized structure deep inside the brain, contains groups of nerve cells that act as control centers affecting sleep and arousal. Within the hypothalamus is the suprachiasmatic nucleus (SCN) – clusters of thousands of cells that receive information about light exposure directly from the eyes and control your behavioral rhythm. Some people with damage to the SCN sleep erratically throughout the day because they are not able to match their circadian rhythms with the light-dark cycle. Most blind people maintain some ability to sense light and are able to modify their sleep/wake cycle.

The brain stem, at the base of the brain, communicates with the hypothalamus to control the transitions between wake and sleep. (The brain stem includes structures called the pons, medulla, and midbrain.) Sleep-promoting cells within the hypothalamus and the brain stem produce a brain chemical called GABA, which acts to reduce the activity of arousal centers in the hypothalamus and the brain stem. The brain stem (especially the pons and medulla) also plays a special role in REM sleep; it sends signals to relax muscles essential for body posture and limb movements, so that we don’t act out our dreams.

The thalamus acts as a relay for information from the senses to the cerebral cortex (the covering of the brain that interprets and processes information from short- to long-term memory). During most stages of sleep, the thalamus becomes quiet, letting you tune out the external world. But during REM sleep, the thalamus is active, sending the cortex images, sounds, and other sensations that fill our dreams.

The pineal gland, located within the brain’s two hemispheres, receives signals from the SCN and increases production of the hormone melatonin, which helps put you to sleep once the lights go down. People who have lost their sight and cannot coordinate their natural wake-sleep cycle using natural light can stabilize their sleep patterns by taking small amounts of melatonin at the same time each day. Scientists believe that peaks and valleys of melatonin over time are important for matching the body’s circadian rhythm to the external cycle of light and darkness.

The basal forebrain, near the front and bottom of the brain, also promotes sleep and wakefulness, while part of the midbrain acts as an arousal system. Release of adenosine (a chemical by-product of cellular energy consumption) from cells in the basal forebrain and probably other regions supports your sleep drive. Caffeine counteracts sleepiness by blocking the actions of adenosine.

The amygdala, an almond-shaped structure involved in processing emotions, becomes increasingly active during REM sleep.

Sleep Stages

There are two basic types of sleep: rapid eye movement (REM) sleep and non-REM sleep (which has three different stages). Each is linked to specific brain waves and neuronal activity. You cycle through all stages of non-REM and REM sleep several times during a typical night, with increasingly longer, deeper REM periods occurring toward morning.

Stage 1 non-REM sleep is the changeover from wakefulness to sleep. During this short period (lasting several minutes) of relatively light sleep, your heartbeat, breathing, and eye movements slow, and your muscles relax with occasional twitches. Your brain waves begin to slow from their daytime wakefulness patterns.
Stage 2 non-REM sleep is a period of light sleep before you enter deeper sleep. Your heartbeat and breathing slow, and muscles relax even further. Your body temperature drops and eye movements stop. Brain wave activity slows but is marked by brief bursts of electrical activity. You spend more of your repeated sleep cycles in stage 2 sleep than in other sleep stages.
Stage 3 non-REM sleep is the period of deep sleep that you need to feel refreshed in the morning. It occurs in longer periods during the first half of the night. Your heartbeat and breathing slow to their lowest levels during sleep. Your muscles are relaxed and it may be difficult to awaken you. Brain waves become even slower.
REM sleep first occurs about 90 minutes after falling asleep. Your eyes move rapidly from side to side behind closed eyelids. Mixed frequency brain wave activity becomes closer to that seen in wakefulness. Your breathing becomes faster and irregular, and your heart rate and blood pressure increase to near waking levels. Most of your dreaming occurs during REM sleep, although some can also occur in non-REM sleep. Your arm and leg muscles become temporarily paralyzed, which prevents you from acting out your dreams. As you age, you sleep less of your time in REM sleep. Memory consolidation most likely requires both non-REM and REM sleep.

Sleep mechanisms

Two internal biological mechanisms–circadian rhythm and homeostasis–work together to regulate when you are awake and sleep.

Circadian rhythms direct a wide variety of functions from daily fluctuations in wakefulness to body temperature, metabolism, and the release of hormones. They control your timing of sleep and cause you to be sleepy at night and your tendency to wake in the morning without an alarm. Your body’s biological clock, which is based on a roughly 24-hour day, controls most circadian rhythms. Circadian rhythms synchronize with environmental cues (light, temperature) about the actual time of day, but they continue even in the absence of cues.
Sleep-wake homeostasis keeps track of your need for sleep. The homeostatic sleep drive reminds the body to sleep after a certain time and regulates sleep intensity. This sleep drive gets stronger every hour you are awake and causes you to sleep longer and more deeply after a period of sleep deprivation. Factors that influence your sleep-wake needs include medical conditions, medications, stress, sleep environment, and what you eat and drink. Perhaps the greatest influence is the exposure to light. Specialized cells in the retinas of your eyes process light and tell the brain whether it is day or night and can advance or delay our sleep-wake cycle. Exposure to light can make it difficult to fall asleep and return to sleep when awakened.

Night shift workers often have trouble falling asleep when they go to bed, and also have trouble staying awake at work because their natural circadian rhythm and the sleep-wake cycle is disrupted. In the case of jet lag, circadian rhythms become out of sync with the time of day when people fly to a different time zone, creating a mismatch between their internal clock and the actual clock.

How Much Sleep Do You Need?

Your need for sleep and your sleep patterns change as you age, but this varies significantly across individuals of the same age. There is no magic “number of sleep hours” that works for everybody of the same age. Babies initially sleep as much as 16 to 18 hours per day, which may boost growth and development (especially of the brain). School-age children and teens on average need about 9.5 hours of sleep per night. Most adults need 7-9 hours of sleep a night, but after age 60, nighttime sleep tends to be shorter, lighter, and interrupted by multiple awakenings. Elderly people are also more likely to take medications that interfere with sleep.

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In general, people are getting less sleep than they need due to longer work hours and the availability of round-the-clock entertainment and other activities.

Many people feel they can “catch up” on missed sleep during the weekend but, depending on how sleep-deprived they are, sleeping longer on the weekends may not be adequate.

Dreaming

Everyone dreams. You spend about 2 hours each night dreaming but may not remember most of your dreams. Its exact purpose isn’t known, but dreaming may help you process your emotions. Events from the day often invade your thoughts during sleep, and people suffering from stress or anxiety are more likely to have frightening dreams. Dreams can be experienced in all stages of sleep but usually are most vivid in REM sleep. Some people dream in color, while others only recall dreams in black and white.

Types of Sleeping Disorders

According to the third edition of the International Classification of Sleep Disorder, insomnia is classified as:

Chronic Insomnia Disorder – The sleep disturbances occur at least three times a week and have been present for the last 3 months.
Short-Term Insomnia Disorder – The sleep disturbances have been present for over a period of 3 months.
Other Insomnia Disorder – Difficulty in initiating or maintaining sleep that does not meet the criteria of chronic insomnia or short-term insomnia disorder.

Causes of Sleeping Disorders

There are different causes for different sleep disorders. Sometimes the cause is unknown. The major causes may be broadly divided into medical conditions, psychological conditions, and other factors.

Medical conditions

Cardiac: heart failure (patient may awaken during the night feeling short of breath)
Neurologic: stroke, central sleep apnea, hypnic jerk, restless leg syndrome, headache, cerebral degenerative disorders[rx]
Endocrine: hyperthyroidism, pregnancy, menopause, diabetes mellitus, vitamin D deficiency[rx]
Pulmonary: obstructive sleep apnea, asthma, chronic obstructive pulmonary disease
Gastrointestinal: GERD
Musculoskeletal: pain from arthritis, fibromyalgia, or any chronic pain[rx]

Psychiatric conditions

Depression: Insomnia is very common among depressed patients. These patients have difficulty falling asleep, nocturnal awakenings, decreased slow-wave sleep, reduced REM latency, and increased REM intensity. Some patients with atypical depression may exhibit hypersomnia.
Anxiety: Anxiety disorders predispose to insomnia. Patients with anxiety have trouble falling asleep, staying asleep, and not feeling rested after sleep.
Phobias and panic attacks: Sleep-related panic attacks do not occur during dreaming, but rather in stage N2 (light sleep) and stage N3 (deep sleep). Post-traumatic stress disorder (PTSD) can produce vivid and terrifying nightmares.
Psychotropic medications: Anti-depressants may interfere with normal REM sleep patterns. Benzodiazepines may produce rebound insomnia, especially in the elderly.

Other factors causing sleep problems

Environmental problems: Shift work may disturb the sleep cycle, as may jet lag. Likewise, loud environmental noise, high temperature, or frequent environmental intrusions may cause sleep deprivation.
Medications: Various medications cause sleep problems. Corticosteroids cause daytime jitters, insomnia, decreased REM sleep. Diuretics cause increased urination during sleep and painful calf cramps during sleep. Similarly, the use of substances such as caffeine, opioids, alcohol, or their withdrawal may result in insomnia.
Aging: Almost half of the elderly population have sleeping problems. The sleep changes in the elderly include difficulty in falling asleep i.e., increased sleep latency, multiple awakenings during the night, and early morning awakening. The elderly people spend very little time in deep, dreamless sleep.
Childhood trauma: Some traumatic childhood experiences (family conflicts or sexual assault) increases the risk of sleep disorders in adulthood like narcolepsy, insomnia, and sleep apnea.

Diagnosis of Sleeping Disorders

History

The symptoms of sleep disorders depend on the specific disorder.

Insomnia – may present as difficulty falling asleep and/or staying asleep. Patients report taking thirty minutes or more to fall asleep (for those with sleep initiation difficulties) or spending thirty minutes or more awake during the night (for those with sleep maintenance difficulties). The diagnosis of insomnia also requires the presence of compromised daytime function, which includes one or more symptoms like fatigue, daytime sleepiness, poor attention, increased accidents, aggression, reduced motivation, or energy. Insomnia can often be a persistent or recurrent condition with exacerbations connected to medical, psychiatric, and psychosocial stressors.
Hypersomnia – is generally seen in adolescents or young adults. The patients with hypersomnia complain of disabling excessive daytime sleepiness. They find it difficult to maintain alertness during the major waking hours of the day with sleep occurring unintentionally or at inappropriate times that interfere with the daily routine.
Narcolepsy – is a chronic neurological disorder caused due to the brain’s inability to control sleep and wakefulness. It is associated with a low cerebrospinal fluid level of orexin-A/hypocretin-1. Patients with narcolepsy complain of excessive chronic daytime sleepiness with varying amount of cataplexy (transient loss of muscle tone in response to intense emotion such as laughter), hallucinations while falling asleep (hypnagogic hallucinations) or hallucinations while waking (hypnopompic hallucinations), and sleep paralysis (inability to move immediately after awakening).
Obstructive sleep apnea (OSA) – is a disorder characterized by obstructive apneas/hypopneas caused due to the laxity of pharyngeal musculature leading to the repetitive collapse of the upper airway during sleep. The patients with OSA complain of excessive daytime sleepiness, morning headaches, poor judgment, impotence, and depression. Loud snoring, gasping, choking, snorting, or interruptions in breathing while sleeping is often reported by their bed partners. OSA is a very common comorbidity in a patient with bipolar disorder. Higher BMI and residual depressive symptoms are the two best independent predictors of OSA in a patient with bipolar disorder.[rx]
Advanced sleep phase syndrome – is a circadian rhythm disorder characterized by an inability to stay awake in the evening (usually after 7 pm). These patients complain of early morning insomnia due to their early bedtime.
Delayed sleep phase syndrome is also a circadian rhythm disorder in which the affected individuals generally go to bed and usually arise two or more hours late than the desired time. These patients often complain of sleep-onset insomnia and excessive morning sleepiness.
REM sleep behavior disorder – is a parasomnia characterized by dream-enactment behaviors that emerge during a loss of REM sleep atonia. The patients with REM sleep behavior disorder show movements such as kicking, punching, arm-flailing, or jumping from bed in response to violent dreams. Patients are generally brought to medical attention due to potentially injurious actions to themselves or their bed partners. The patient can recall the dream if he awakens during the episode. This disorder may be associated with other medical conditions such as Parkinson’s disease, Lewy body dementia, or multiple system atrophy.
Night terrors – are most common in children aged 2 to 12 years of age, which usually resolve spontaneously as the child ages. It occurs in non-REM sleep. Parents usually complain of their child exhibiting features like screaming, intense fear, and flailing while still asleep during an episode of the night terror. There is no memory of the event.
Nightmare is parasomnia – that occurs during REM sleep, usually in the middle of the night and early morning. During a nightmare, the person may scream and yell out things. The difference of a nightmare with a night terror is that the person can become fully alert when awakened during a nightmare. Also, there is a memory of the event in a nightmare i.e., and a person can recall a nightmare.
Restless leg syndrome – is a sleep movement disorder in which the patients have an uncomfortable sensation and an urge to move the legs while trying to fall asleep. The symptoms are relieved by walking or moving the legs.

Physical Examination

Signs of sleep disorders are as follows:

Poor concentration
Drowsiness
Slowed reaction time
Hypertension (which can be caused by sleep apnea)
Poor growth, enlarged tonsils, and narrowed airway (findings of OSA)

Evaluation

A variety of information is required to evaluate sleep problems. After a detailed medical history, medication history, and physical examination; some of the investigations appropriate to diagnose sleep disorders are as follows:

Sleep diary – The sleep diary, or sleep log, is a subjective paper record of sleep and wakefulness over a period of weeks to a month. Patients should record the detailed description of sleep, such as bedtime, duration until sleep onset, the number of awakenings, duration of awakenings, and nap times.
Sleep studies – Objective measures of sleep may be obtained by sleep studies such as electroencephalography (EEG) or polysomnography (PSG). PSG is largely regarded as the gold standard for the diagnosis of OSA and other sleep disorders. During PSG, numerous monitoring devices are connected to the patient, and the patient is allowed to sleep. Various physiologic parameters such as respiratory effort, sleep stages, electrocardiography, airflow, body position, and limb movements are assessed. The information obtained from these parameters helps to diagnose various REM & NREM sleep disorders as well as determine the causes of sleep disturbance.

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Laboratory studies: Some of the lab studies appropriate for those with sleep disorders include:

Hemoglobin and hematocrit
Arterial blood gases (ABG)
Thyroid function tests
Drug and alcohol toxicity screening
Iron studies
CRP (increased in patients with OSA).[rx]

Others Test

Overnight oximetry – This involves the use of a probe that is worn on the finger or earlobe, which continuously measures oxygen levels and heart rate. It identifies individuals who are at risk for nocturnal breathing disorders such as sleep apnea.
Actigraphy – In this test, a device called the actigraph is worn on the wrist like a watch. The signals are detected when there is movement. Very few to no signals are recorded during sleep/inactivity. This device can be used to assess sleep-wake cycles or circadian rhythm over an extended period of time and thus can be used to diagnose advanced or delayed sleep phase syndrome.
Multiple sleep latency testing (MSLT) – This is an objective test that determines the degree of sleepiness. This test is often called a nap study. On the day following an overnight PSG study, the patient is asked to take four or five naps over a period of 8-10 hours. Each nap lasts about 20 minutes. These tests are useful in identifying excessive daytime sleepiness, which can be present in various disorders such as sleep apnea, hypersomnia, and narcolepsy.
Indices and scoring systems – If there is a suspicion of depression causing insomnia, Beck Depression Inventory can be used. Similarly, tools like a structured clinical interview for sleep disorders (SCISD) is a brief, reliable interview assessment tool for sleep disorders.[rx]

Treatment of Sleeping Disorders

Treatments for sleep disorders depend on the type of sleep disorder. Treatment of insomnia can be broadly categorized into non-pharmacological and pharmacological treatments.

Non-pharmacological treatments

Cognitive-behavioral therapy (CBT) – these are psychological and behavioral techniques that can be helpful for treating insomnia. Depending on the specific symptoms, some of the techniques employed in CBT are:
Sleep restriction therapy (SRT) – SRT limits the total time allowed in bed so that the drive to sleep increases.
Stimulus control therapy – it helps in changing sleep habits so that the patients don’t have difficulty falling asleep. Patients should not go to bed until they are sleepy. Also, the bed should be used only for sleeping and not for watching television or reading books.
Relaxation training – Relaxation techniques may be implemented before sleep. Meditation and breathing exercises are some of the relaxation techniques. It begins with being in a comfortable position and closing eyes. The mind and thoughts should be redirected towards a peaceful image, and relaxation should be allowed to spread throughout the body.
Hypnosis – the hypnotherapist uses different therapeutic techniques like verbal repetition and mental images, which makes the patient feel calm and relaxed, promoting restful sleep.
Sleep Hygiene – Sleep hygiene includes educating the patients about lifestyle modifications like limiting the daytime naps, avoiding late-night dinner or evening intake of alcohol, caffeine, or smoking. It also involves encouraging them to adopt a healthy diet, exercise regime and maintain a regular sleep and wake time schedule. The sleep hygiene index and the sleep hygiene awareness and practice scales can be used to assess sleep hygiene. However, sleep hygiene alone is ineffective in managing patients with chronic insomnia and should be used with other aspects of cognitive behavior therapy.
Sleep Restriction Therapy – This therapy depends on limiting the number of sleep hours with the idea that a reduced sleep time might improve the sleep drive and result in a consolidated sleep. This therapy might increase the chances of daytime sleepiness due to the sleep loss associated with the therapy. Based on the results, the total nighttime sleep can be gradually extended later.
Stimulus Control Therapy – The patient should be advised to restrict the maladaptive behaviors like eating or reading in bed, late-night use of digital devices in the bed, and go to bed to sleep only when feeling extremely sleepy.
Relaxation Therapy – Regular practice of breathing exercises, meditation or yoga can help to improve the sleeping pattern and reduce underlying anxiety and stress.

Pharmacologic therapy

Histamine type 1 receptor blockers – due to their sedative effects, these drugs can be helpful in patients with sleep disorders. However, due to their anticholinergic effect, these drugs should be avoided in the elderly. Examples include chlorpheniramine and diphenhydramine.
Benzodiazepines (BZD) – these drugs are the mainstay in the treatment of insomnia. The drugs bind to a special benzodiazepine site on the gamma-aminobutyric acid (GABA) receptor complex, enhancing the activity of neurotransmitters. These drugs suppress REM sleep, reduces stages 3 & 4 sleep while increasing stage 2 sleep. Examples include flurazepam and temazepam.
Non-benzodiazepine hypnotics – these agents are used for the treatment of acute and short-term insomnia. These drugs have non-BZD like chemical structures but interact with the GABA-BZD receptor, causing sedation. Examples include zolpidem and zaleplon.
Melatonin receptor agonists – the melatonin receptors MT1 and MT2 are implicated in regulating sleepiness and the sleep-wake cycle. Melatonin receptor agonists act on these receptors and hence improve sleep through the endogenous regulating system. These drugs are used in circadian rhythm sleep disorders, jet lag, delayed sleep-wake phase disorder (insomnia with difficulty in sleep onset).[rx] [rx][rx]Example includes ramelteon.
Orexin receptor antagonists – orexin promotes wakefulness. Thus, the antagonism of this receptor helps in sleep. An example includes suvorexant.

Other interventions

Sleep apnea can be alleviated by losing weight, the use of continuous positive airway pressure (CPAP), and, sometimes, surgical treatment. The drug solriamfetol, selective dopamine, and norepinephrine reuptake inhibitor can be used to increase wakefulness in patients with OSA who have excessive sleepiness.[rx]
A number of medications can be used for the treatment of narcolepsy. Modafinil, a non-amphetamine stimulant that promotes wakefulness, is considered as first-line therapy for narcolepsy as it reduces daytime sleepiness, is well tolerated, and has less abuse potential compared to traditional stimulants (amphetamines, methylphenidate). These traditional drugs are second-line drugs. Patients with significant cataplexy may benefit from REM suppressing drugs such as anti-depressants and sodium oxybate.
Light-phase shift therapy is useful for sleep disturbances associated with circadian rhythm abnormalities.[rx] Patients may be exposed to bright light to help normalize the sleep schedule.
Gabapentin enacarbil significantly improves restless leg syndrome and hence alleviates sleep disturbance.[rx]

Drugs acting on GABA-A receptors

The benzodiazepines (BZD) and benzodiazepine receptor agonists (BzRA or non-BZD) both act on the GABA receptor sites thereby exerting sedative, anxiolytic, muscle relaxant, and hypnotic effects. One significant difference between the 2 groups is the receptor affinity towards different subtypes of GABA alpha subunit. While all the BZD have similar affinity to various subtypes of alpha subunits, BzRA has a varying affinity to different subtypes of alpha subunits. For example, zolpidem, zopiclone, and zaleplon have higher affinity to alpha-1 subunit and lower affinity to alpha-2 and alpha-3 subunit; whereas, eszopiclone has a higher affinity to alpha-2 and alpha-3 subunit of GABA receptor. The adverse effects associated with BZD like rapid development of tolerance, the risk of abuse or dependence, the occurrence of rebound insomnia after drug discontinuation, and cognitive impairment further limit the use of BZD over BzRA.

The benzodiazepine receptor agonist (non-BZD or BzRA) became available in the United States in 1992 and since then have been used for the management of insomnia. The benzodiazepine receptor agonists are rapidly absorbed, relatively short-acting (as compared to benzodiazepines), and have relatively better side effect profiles. They are effective in treating sleep onset insomnia, sleep maintenance insomnia, or both.[rx],[rx]

Zolpidem binds selectively to alpha one subtype of GABA-A receptor. It has a short half-life of 2.2 hours and is available in immediate-release (IR) formulation of 5-mg and 10-mg doses, which are effective for the treatment of short-term insomnia. The controlled-release (CR) form is available in 6.25-mg and 12.5-mg dosage for sleep onset and sleeps maintenance insomnia. A sublingual form (doses in male 3.5 mg and female 1.75 mg) is available for the treatment of middle of night awakenings (MOTN) and difficulty in returning to sleep and should be used if there is a minimum of 4 more hours of intended sleep time. The adverse effects associated with zolpidem are headache, falls, somnolence, and antegrade amnesia.

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Zaleplon has the shortest duration of action with a half-life of one hour and is available at the doses of 5 mg, 10 mg, 20 mg for the treatment of insomnia. The adverse effects associated with it are headache, drowsiness, nausea, and worsening of depressive symptoms in patients with comorbid depressive disorder.

Eszopiclone helps to improve sleep efficiency, daytime functioning along with a reduction in sleep onset latency with wakefulness after sleep onset. It is used for the management of sleep-onset insomnia (2 mg) and sleeps maintenance (3 mg) insomnia. It acts on the alpha-2, and alpha-3 receptors subtype of the GABA-A receptors, thereby exerting anxiolytic and antidepressant effects respectively, and hence, is effective in the management of insomnia with comorbid depression or generalized anxiety disorder. Common adverse effects associated with eszopiclone are unpleasant metallic taste, headache, dizziness, and somnolence.

Drugs Acting on Melatonin Receptors

Melatonin is a natural hormone produced by the pineal gland. The circadian system in the hypothalamus and the suprachiasmatic nucleus regulates the levels of this hormone throughout the day and night. Melatonin is available over the counter and is approved by Food and Drug Administration (FDA) for the treatment of insomnia, especially in older adults. A dose range of 2 to 8 mg is effective in treating circadian rhythm sleep-wake disorders. However, food can delay the absorption of melatonin, and a gap should be maintained between the last meal of the day and the intake of melatonin.

Ramelteon decreases the sleep latency by acting on the melatonin MT1 and MT2 receptors in the suprachiasmatic nucleus with higher affinity than melatonin itself. A dosage of 8 mg is recommended by the Food and Drug Administration (FDA) for the management of sleep-onset insomnia. It exerts minimal adverse effects including somnolence, fatigue, and dizziness.

Tasimelteon is another melatonin receptor agonist effective in improving sleep initiation and maintenance particularly in blind patients with non-24-hour sleep-wake disorders.

Drugs acting as Orexin Receptor Antagonist

Suvorexant is a dual orexin receptor antagonist (OX1 and OX2 receptor) which counteracts the orexin/hypocretin mediated nighttime awakening. It is effective in doses of 5 mg, 10 mg, 15 mg, and 20 mg for the management of sleep onset and sleep maintenance insomnia. A dose of 15 mg and 20 mg has shown improvement in total sleep time and a reduction in sleep onset latency. However, the FDA does not recommend a higher dose of 30 mg or 40 mg of suvorexant because of safety concerns, with an increased risk of next-day driving difficulty, increased daytime somnolence and narcolepsy-like symptoms (hypnogogic-hypnopompic hallucinations, cataplexy, and vivid dreams). Also, suvorexant is contraindicated in patients with narcolepsy because of possible underlying mechanisms of orexin antagonism.

Drugs Acting as Histamine-1 Receptor Antagonist

Doxepin is a tricyclic antidepressant, but at a low dose of 3 mg and 6 mg, it is effective in the management of sleep maintenance insomnia. It causes improvement in total sleep time, wakefulness after sleep onset and sleep efficiency. At low doses (3 mg and 6 mg), Doxepin acts as pure H-1 receptor antagonist being 800 times more potent than diphenhydramine for H-1 receptors, and at high doses of 25 mg to 300 mg daily (antidepressant dosage), it exerts antihistaminic, antiserotonergic, anticholinergic and antiadrenergic activity. The adverse effects associated with doxepin at low doses are headache and somnolence.

Off-Label Drugs

Antidepressants: Trazodone, mirtazapine, and amitriptyline are most commonly used antidepressants for the management of insomnia at low doses mainly because of their antihistaminic effect. Studies have shown a 50 mg once a day dose of trazodone has proved to be effective in improving sleep latency, wakefulness after sleep onset and duration of sleep.

Atypical antipsychotics: Olanzapine and quetiapine can be useful in the treatment of insomnia with comorbid psychotic conditions. They exert a sedative effect at low doses by their antihistaminic and antiserotonergic activity.

Anticonvulsants: Gabapentin has shown to improve the sleep efficiency and decrease the wakefulness after sleep onset. It can be effective in managing insomnia in patients with alcohol dependence. Pregabalin increases the total sleep time, stage N3, sleep efficiency and decreases the sleep onset latency and REM sleep. It is helpful in improving sleep in patients with generalized anxiety disorder and fibromyalgia.[rx]

The Role of Genes and Neurotransmitters

Chemical signals to sleep

Clusters of sleep-promoting neurons in many parts of the brain become more active as we get ready for bed. Nerve-signaling chemicals called neurotransmitters can “switch off” or dampen the activity of cells that signal arousal or relaxation. GABA is associated with sleep, muscle relaxation, and sedation. Norepinephrine and orexin (also called hypocretin) keep some parts of the brain active while we are awake. Other neurotransmitters that shape sleep and wakefulness include acetylcholine, histamine, adrenaline, cortisol, and serotonin.

Genes and sleep

Genes may play a significant role in how much sleep we need. Scientists have identified several genes involved with sleep and sleep disorders, including genes that control the excitability of neurons, and “clock” genes such as Per, tim, and Cry that influence our circadian rhythms and the timing of sleep. Genome-wide association studies have identified sites on various chromosomes that increase our susceptibility to sleep disorders. Also, different genes have been identified with such sleep disorders as familial advanced sleep-phase disorder, narcolepsy, and restless legs syndrome. Some of the genes expressed in the cerebral cortex and other brain areas change their level of expression between sleep and wake. Several genetic models–including the worm, fruit fly, and zebrafish–are helping scientists to identify molecular mechanisms and genetic variants involved in normal sleep and sleep disorders. Additional research will provide better understand of inherited sleep patterns and risks of circadian and sleep disorders.

Sleep studies

Your health care provider may recommend a polysomnogram or other test to diagnose a sleep disorder. A polysomnogram typically involves spending the night at a sleep lab or sleep center. It records your breathing, oxygen levels, eye and limb movements, heart rate, and brain waves throughout the night. Your sleep is also video and audio recorded. The data can help a sleep specialist determine if you are reaching and proceeding properly through the various sleep stages. Results may be used to develop a treatment plan or determine if further tests are needed.

Tracking Sleep Through Smart Technology

Millions of people are using smartphone apps, bedside monitors, and wearable items (including bracelets, smart watches, and headbands) to informally collect and analyze data about their sleep. Smart technology can record sounds and movement during sleep, journal hours slept, and monitor heart beat and respiration. Using a companion app, data from some devices can be synced to a smartphone or tablet, or uploaded to a PC. Other apps and devices make white noise, produce light that stimulates melatonin production, and use gentle vibrations to help us sleep and wake.

Tips for Getting a Good Night’s Sleep

Getting enough sleep is good for your health. Here are a few tips to improve your sleep:

Set a schedule – go to bed and wake up at the same time each day.

Exercise 20 to 30 minutes a day but no later than a few hours before going to bed.

Avoid caffeine and nicotine late in the day and alcoholic drinks before bed.

Relax before bed – try a warm bath, reading, or another relaxing routine.

Create a room for sleep – avoid bright lights and loud sounds, keep the room at a comfortable temperature, and don’t watch TV or have a computer in your bedroom.

Don’t lie in bed awake. If you can’t get to sleep, do something else, like reading or listening to music, until you feel tired.

See a doctor if you have a problem sleeping or if you feel unusually tired during the day. Most sleep disorders can be treated effectively.

References

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Sleeping Disorders – What About You Need To Knows

Sleeping Disorders – What About You Need To Knows

Anatomy of Sleep

Sleep Stages

Sleep mechanisms