Definition and Classifications

Definition

Insomnia is thesubjectiveperceptionPerceptionThe process by which the nature and meaning of sensory stimuli are recognized and interpreted.Psychiatric Assessment of difficulty withsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep initiation, duration,consolidationConsolidationPulmonary Function Tests, orqualityQualityActivities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps.Quality Measurement and Improvement despite adequate opportunity forsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep, resulting in daytime functional impairment.

Classifications

By duration: 

• Acute insomnia (< 3 months):
  • Transient or short-term insomnia
  • Due to a certaintriggerTriggerThe type of signal that initiates the inspiratory phase by the ventilatorInvasive Mechanical Ventilation (i.e.,sleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep environment, illness) and usually associated withanxietyAnxietyFeelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders.Generalized Anxiety Disorder or life change
  • Can evolve to persistent or chronic form
• Chronic insomnia (≥ 3 months)
  • Includes primary and comorbid insomnia
  • Muscular weakness,hallucinationsHallucinationsSubjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders.Schizophrenia, and doublevisionVisionOphthalmic Exam may be present.

By howsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep is impaired:

• Sleep-onset insomnia: difficulty falling asleep at the beginning of the night
• Sleep-maintenance insomnia: difficulty staying asleep
• Early-morning awakening: waking too early and having difficulty getting back tosleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep
• Paradoxical insomnia:
  • Sleep-state misperception
  • DissociationDissociationDefense Mechanisms between patient’s self-reportedqualityQualityActivities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps.Quality Measurement and Improvement ofsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep and the findings from objectivepolysomnographyPolysomnographySimultaneous and continuous monitoring of several parameters during sleep to study normal and abnormal sleep. The study includes monitoring of brain waves, to assess sleep stages, and other physiological variables such as breathing, eye movements, and blood oxygen levels which exhibit a disrupted pattern with sleep disturbances.Physiology of Sleep (which are normal)

Epidemiology and Etiology

Epidemiology

• At least 30% of ambulatorypatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship report symptoms of insomnia.
• More common in women and older adults
• IncreasedprevalencePrevalenceThe total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time.Measures of Disease Frequency in those who are unemployed, divorced, or widowed

Risk factors

• InadequatesleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep hygiene:
  • Irregular bedtime schedule
  • Using bed for work, eating, or watching television
  • Naps, especially after 3 pm
  • Stimulating activities (e.g., exercising) before bedtime
• Environmental factors such as noise, light, and extreme temperatures
• UnderlyingsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep disorder (e.g.,restless legsRestless legsA disorder characterized by aching or burning sensations in the lower and rarely the upper extremities that occur prior to sleep or may awaken the patient from sleep.Polyneuropathy syndrome)
• Behavioral insomnia (i.e., alteration of thesleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep cycle) such as from jet lag or shift work
• Medical conditions or illnesses:
  • DiabetesDiabetesDiabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance.Diabetes Mellitus 
  • GERDGERDGastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn).Gastroesophageal Reflux Disease (GERD)
  • HyperthyroidismHyperthyroidismHypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate.Thyrotoxicosis and Hyperthyroidism
  • AsthmaAsthmaAsthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea.Asthma 
  • Alzheimer diseaseAlzheimer diseaseAs the most common cause of dementia, Alzheimer disease affects not only many individuals but also their families. Alzheimer disease is a progressive neurodegenerative disease that causes brain atrophy and presents with a decline in memory, cognition, and social skills.Alzheimer Disease 
  • MenopauseMenopauseMenopause is a physiologic process in women characterized by the permanent cessation of menstruation that occurs after the loss of ovarian activity. Menopause can only be diagnosed retrospectively, after 12 months without menstrual bleeding.Menopause (i.e., vasomotor symptoms)
  • Chronic painChronic painAching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain.Pain Management
• Mental health disorders:
  • Depression
  • AnxietyAnxietyFeelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders.Generalized Anxiety Disorder disorders 
  • PTSDPTSDPosttraumatic stress disorder is a psychiatric illness characterized by overwhelming stress and anxiety experienced after exposure to a life-threatening event. Symptoms last more than 1 month and involve re-experiencing the event as flashbacks or nightmares, avoiding reminders of the event, irritability, hyperarousal, and poor memory and concentration.Posttraumatic Stress Disorder (PTSD)
• Substance use disorder/medication-induced:
  • CaffeineCaffeineA methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine’s most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling.Stimulants 
  • NicotineNicotineNicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.Stimulants 
  • Alcohol 
  • AmphetaminesAmphetaminesAnalogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopressin, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation.Stimulants
  • ModafinilModafinilStimulants
  • Benzodiazepine oropioid withdrawalOpioid withdrawalOpioid Use Disorder

Pathophysiology

• In thebrainBrainThe part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem.Nervous System: Anatomy, Structure, and Classification, several structures are involved in controlling wakefulness andsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep.
• Sleep-promoting cells in the brainstem andhypothalamusHypothalamusThe hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems.Hypothalamus (containing the suprachiasmaticnucleusNucleusWithin a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus.The Cell: Organelles (SCN)) facilitate reduced activity of arousal centers.
• Neurotransmitters that play major roles in insomnia:
  • Decreased inhibitory neurotransmitter (GABAGABAThe most common inhibitory neurotransmitter in the central nervous system.Receptors and Neurotransmitters of the CNS) in the brainstem 
  • Activation of SCN and inhibition of melatonin produced by thepineal glandPineal glandA light-sensitive neuroendocrine organ attached to the roof of the third ventricle of the brain. The pineal gland secretes melatonin, other biogenic amines and neuropeptides.Hormones: Overview and Types
  • Increased level of stresshormonesHormonesHormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments.Hormones: Overview and Types such ascortisolCortisolGlucocorticoids 
• Hyperarousal theory:
  • IncreasedbrainBrainThe part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem.Nervous System: Anatomy, Structure, and Classification arousal during non-rapid eye movement (NREMNREMPhysiology of Sleep)sleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep
  • Activation of keybrainBrainThe part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem.Nervous System: Anatomy, Structure, and Classification areas, which, once activated, cause inhibition ofbrainBrainThe part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem.Nervous System: Anatomy, Structure, and Classification pathways that inducesleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep
• Cognitive-behavioral model:
  • Predisposing conditions (e.g.,anxietyAnxietyFeelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders.Generalized Anxiety Disorder) interact with precipitating factors such as illness and bereavement, increasing the risk of insomnia.
  • Perpetuating factors (e.g., daytime behaviors, sleep-wake schedule) contribute to maintaining insomnia.
  • The “3P” model: predisposition, precipitation, and perpetuation of chronic insomnia 

Clinical Presentation and Diagnosis

Symptoms

• Difficulty falling asleep
• Daytime sleepinessDaytime sleepinessNarcolepsy
• GeneralfatigueFatigueThe state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.Fibromyalgia and tiredness
• Problems with concentration ormemoryMemoryComplex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory.Psychiatric Assessment
• Irritability
• Increased errors or accidents

Diagnostic aids

• History:
  • Medical and psychiatric history
  • SleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep history
  • Interview of the bed partner about the quantity andqualityQualityActivities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps.Quality Measurement and Improvement ofsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep
• Physical and neurologic exam (helps determine comorbid conditions)
• Self-reportscreeningScreeningPreoperative Care tools (e.g.,sleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep problems questionnaire)
• SleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep diary: kept over 2–4 weeks to assess patterns ofsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep  
• PolysomnographyPolysomnographySimultaneous and continuous monitoring of several parameters during sleep to study normal and abnormal sleep. The study includes monitoring of brain waves, to assess sleep stages, and other physiological variables such as breathing, eye movements, and blood oxygen levels which exhibit a disrupted pattern with sleep disturbances.Physiology of Sleep:
  • Not required for diagnosis
  • Utilized to rule out othersleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep disorders

Diagnostic criteria

• Trouble falling asleep or staying asleep
• Awakening earlier than intended with difficulty returning tosleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep
• Difficulty functioning:
  • Social impairment
  • Occupational impairment
  • Behavioral impairment 
• Frequency ofsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep symptoms ≥ 3 nights/week
• Duration ofsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep symptoms ≥ 3 months
• Symptoms not due to limitedsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep opportunities
• Absence of any comorbidsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep disorder
• Absence of any medical illness, psychiatric condition, or substance use disorder that would contribute to disorderedsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep.

Management

Nonpharmacologic treatment

• Short-term or acute insomnia:
  • Identify the stressor(s) and address accordingly.
  • Use of medication(s):
    • If insomnia interferes with daytime function
    • Temporary
• Chronic Insomnia:
  • ImprovesleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep hygiene:
    • Avoid alcohol, caffeinated drinks, and large meals at least 4 hours before bedtime.
    • MaintainregularRegularInsulin exercise patterns but no exercising too close to bedtime (3 hours). 
    • Avoid napping or daytime sleeping. 
    • Use bed only forsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep/sexSexThe totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism.Gender Dysphoria (no eating/television/cellphone in bed).
    • Reduce light exposure around bedtime.
  • Cognitive-behavioral therapyCognitive-behavioral therapyCognitive-behavioral therapy corrects faulty assumptions and tries to replace maladaptive behavior with healthier alternatives.Psychotherapy:
    • 1st line of treatment 
    • Goal is to increasesleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep efficiency, address maladaptive thoughts, and promote a stable routine ofsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep/wake times. 
    • Set a time forsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep each day (i.e., follow asleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep schedule)
    • SleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep restriction: reduce time in bed to total hours ofsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep
    • Stimulus control: if anxious when unable tosleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep, should get out of bed 
    • SleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep hygiene
• Treat any underlyingpainPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways, depression, or othercomorbiditiesComorbiditiesThe presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival.St. Louis Encephalitis Virus before intensivesleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep treatment.

Pharmacologic treatment

• Hypnotic benzodiazepinereceptorReceptorReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors agonists (BZRAs):
  • Mechanism: acts onGABAGABAThe most common inhibitory neurotransmitter in the central nervous system.Receptors and Neurotransmitters of the CNSreceptorReceptorReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors without specific affinity to different subtypes ofGABAGABAThe most common inhibitory neurotransmitter in the central nervous system.Receptors and Neurotransmitters of the CNS
  • High risk oftoleranceTolerancePharmacokinetics and Pharmacodynamics, abuse, and dependence as well as cognitive impairments linked with long-term use 
  • Examples:
    • TemazepamTemazepamA benzodiazepine that acts as a gamma-aminobutyric acid modulator and anti-anxiety agent.Benzodiazepines
    • ClonazepamClonazepamAn anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of gamma-aminobutyric acid receptor responses.Benzodiazepines
    • TriazolamTriazolamA short-acting benzodiazepine used in the treatment of insomnia. Its use at lower doses with appropriate care and labeling has been reaffirmed by the fda and most other countries.Benzodiazepines 
• Nonbenzodiazepine BZRAs:
  • Mechanism:
    • BenzodiazepinereceptorReceptorReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors agonists that act onGABAGABAThe most common inhibitory neurotransmitter in the central nervous system.Receptors and Neurotransmitters of the CNSreceptorReceptorReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors (similar tobenzodiazepinesBenzodiazepinesBenzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity.Benzodiazepines)
    • Selective affinity (GABA-A subunit subtypes), which reduces side effects
  • Fewer adverse effects and abuse potential thanbenzodiazepinesBenzodiazepinesBenzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity.Benzodiazepines
  • Examples:
    • Zolpidem
    • Zaleplon
    • Eszopiclone 
• Dual orexinreceptorReceptorReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors antagonists
  • Mechanism:
    • Orexin or hypocretin system promotes arousal or wakefulness.
    • OrexinreceptorReceptorReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors antagonists counteract the orexin-mediated nighttime awakening. 
  • Examples: lemborexant, suvorexant 
• Melatonin agonists:
  • Mechanism: Melatonin is a natural hormone associated with the establishment of thecircadian rhythmCircadian RhythmThe regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli.Cranial Nerve Palsies and sleep-wake cycle. 
  • Examples:
    • Melatonin: natural hormone (over the counter) 
    • Ramelteon: highly selective melatoninreceptorReceptorReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors agonist with higher affinity and selectivity than melatonin   
• HistaminereceptorReceptorReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors antagonist:
  • Mechanism: H1receptorReceptorReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors antagonist producing sedation
  • Example:doxepinDoxepinA dibenzoxepin tricyclic compound. It displays a range of pharmacological actions including maintaining adrenergic innervation. Its mechanism of action is not fully understood, but it appears to block reuptake of monoaminergic neurotransmitters into presynaptic terminals. It also possesses anticholinergic activity and modulates antagonism of histamine h(1)- and h(2)-receptors.Tricyclic Antidepressants
• Antidepressants with sedative properties:
  • Exact mechanism unknown but thought to work through antihistamine andserotoninSerotoninA biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity.Receptors and Neurotransmitters of the CNS effects 
  • Off-label use  
  • Examples:
    • TrazodoneTrazodoneA serotonin uptake inhibitor that is used as an antidepressant agent. It has been shown to be effective in patients with major depressive disorders and other subsets of depressive disorders. It is generally more useful in depressive disorders associated with insomnia and anxiety.Serotonin Reuptake Inhibitors and Similar Antidepressants
    • Mirtazapine
    • AmitriptylineAmitriptylineTricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the reuptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antagonize cholinergic and alpha-1 adrenergic responses to bioactive amines.Tricyclic Antidepressants
    • DoxepinDoxepinA dibenzoxepin tricyclic compound. It displays a range of pharmacological actions including maintaining adrenergic innervation. Its mechanism of action is not fully understood, but it appears to block reuptake of monoaminergic neurotransmitters into presynaptic terminals. It also possesses anticholinergic activity and modulates antagonism of histamine h(1)- and h(2)-receptors.Tricyclic Antidepressants

Differential Diagnosis

• NarcolepsyNarcolepsyNarcolepsy is a neurological sleep disorder marked by daytime sleepiness and associated with cataplexy, hypnagogic hallucinations, and sleep paralysis. There are 2 types of narcolepsy: type 1 is associated with cataplexy and type 2 has no association with cataplexy.Narcolepsy:asleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep disorder characterized by excessivedaytime sleepinessDaytime sleepinessNarcolepsy and falling asleep at inappropriate times.NarcolepsyNarcolepsyNarcolepsy is a neurological sleep disorder marked by daytime sleepiness and associated with cataplexy, hypnagogic hallucinations, and sleep paralysis. There are 2 types of narcolepsy: type 1 is associated with cataplexy and type 2 has no association with cataplexy.Narcolepsy is associated withhallucinationsHallucinationsSubjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders.Schizophrenia (hypnagogic and hypnopompic, which occur upon falling and waking fromsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep, respectively) andcataplexyCataplexyA condition characterized by transient weakness or paralysis of somatic musculature triggered by an emotional stimulus or physical exertion. Cataplexy is frequently associated with narcolepsy. During a cataplectic attack, there is a marked reduction in muscle tone similar to the normal physiologic hypotonia that accompanies rapid eye movement sleep (sleep, rem).Narcolepsy (emotionally triggered loss ofmuscle toneMuscle toneThe state of activity or tension of a muscle beyond that related to its physical properties, that is, its active resistance to stretch. In skeletal muscle, tonus is dependent upon efferent innervation.Skeletal Muscle Contraction).NarcolepsyNarcolepsyNarcolepsy is a neurological sleep disorder marked by daytime sleepiness and associated with cataplexy, hypnagogic hallucinations, and sleep paralysis. There are 2 types of narcolepsy: type 1 is associated with cataplexy and type 2 has no association with cataplexy.Narcolepsy must be ruled out via history andsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep study before diagnosis of primary insomnia.
• Circadian rhythmCircadian RhythmThe regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli.Cranial Nerve Palsies sleep-wake disorders: a group of conditions marked by recurrent patterns ofsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep disruption. These conditions can be due to an alteration of the circadian system or a misalignment between the innercircadian rhythmCircadian RhythmThe regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli.Cranial Nerve Palsies and thesleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep environment. Delayed sleep-wake phase disorder manifests as delayed onset ofsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep and awakening. ThesleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of SleepqualityQualityActivities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps.Quality Measurement and Improvement and duration are preserved. In advanced sleep-wake phase disorder, there is earlysleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep onset and awakening. Diagnosis is generally clinical. Unlike in these disorders, in insomnia, the patient has difficulty falling asleep at any time. 
• HyperthyroidismHyperthyroidismHypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate.Thyrotoxicosis and Hyperthyroidism: caused by an excess ofthyroidThyroidThe thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck.Thyroid Gland: AnatomyhormonesHormonesHormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments.Hormones: Overview and TypesT3T3A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5′ position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly t3.Thyroid Hormones andT4T4The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism.Thyroid Hormones. Clinical features ofhyperthyroidismHyperthyroidismHypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate.Thyrotoxicosis and Hyperthyroidism are mostly due to the body’s increased metabolic rate.SleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep disturbance is one of the important manifestations of this disease. Basic laboratory studies (thyroid-stimulating hormoneThyroid-stimulating hormoneA glycoprotein hormone secreted by the adenohypophysis. Thyrotropin stimulates thyroid gland by increasing the iodide transport, synthesis and release of thyroid hormones (thyroxine and triiodothyronine).Thyroid Hormones) should rule out this disorder prior to making a diagnosis of primary insomnia
• GeneralizedanxietyAnxietyFeelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders.Generalized Anxiety Disorder disorder: chronic multiple worries that are irrational and uncontrollable. The disorder is associated withfatigueFatigueThe state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.Fibromyalgia, low concentration, restlessness, irritability, andsleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep disturbance. OtheranxietyAnxietyFeelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders.Generalized Anxiety Disorder disorders (e.g.,phobiasPhobiasNeurological Examination, socialanxietyAnxietyFeelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders.Generalized Anxiety Disorder disorder,PTSDPTSDPosttraumatic stress disorder is a psychiatric illness characterized by overwhelming stress and anxiety experienced after exposure to a life-threatening event. Symptoms last more than 1 month and involve re-experiencing the event as flashbacks or nightmares, avoiding reminders of the event, irritability, hyperarousal, and poor memory and concentration.Posttraumatic Stress Disorder (PTSD)) can also causesleepSleepA readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Physiology of Sleep disturbance. Full history should excludeanxietyAnxietyFeelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders.Generalized Anxiety Disorder disorders prior to making a diagnosis of primary insomnia.

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