You are leaving Medscape Education
Cancel Continue
Log in to save activities Your saved activities will show here so that you can easily access them whenever you're ready. Log in here CME & Education Log in to keep track of your credits.


Common Comorbidities of Insomnia



A recent National Institutes of Health (NIH) State-of-the-Science Conference statement defined insomnia as a complaint of disturbed sleep in the presence of adequate opportunity and circumstance for sleep.[1] This definition distinguishes insomnia from sleep deprivation, in which sleep is curtailed as a result of limited opportunity for sleep. Insomnia may involve difficulty in initiating sleep, in maintaining sleep, or of waking up too early. Sleep may also be nonrestorative or poor in quality.

Insomnia can be subdivided into primary and comorbid types. The former is also referred to as an insomnia syndrome, an independent disorder which is thought to arise from behavioral factors, such as negative conditioning, or physiologic factors, such as hyperarousal. Evidence of hyperarousal has been noted in a variety of body functions, including brain waves, the hypothalamic pituitary axis, the sympathetic nervous system, in cognition, and in metabolic rate.[2] In contrast, comorbid insomnia arises in the context of another disorder. Historically, this was referred to as "secondary insomnia." However, the NIH State of the Science Conference report proposed use of the term "comorbid" because the direction of causality is not always clear when insomnia exists in the context of other conditions.[1] Insomnia can be caused by other conditions and can be independent of them completely. Conceivably, insomnia can also cause the disorders with which it coexists. Primary insomnia is less prevalent than comorbid insomnia.[3]

Comorbid Conditions

Psychiatric Disorders

As a group, psychiatric disorders represent the most common comorbidities in insomnia. A psychiatric diagnosis is present in 40% of people with insomnia.[4] Common psychiatric comorbidities include substance use disorders, anxiety disorders, and mood disorders. The persistence of insomnia, even in the absence of psychiatric disorders, is a strong predictor of the emergence of future psychiatric disorders. Therefore, clinicians should maintain a high index of suspicion for the possibility of the existence, or emergence, of a psychiatric disorder in those with chronic insomnia. Symptoms that indicate the potential for certain psychiatric disorders include nocturnal panic attacks (sudden surges of anxiety, tachycardia, diaphoresis, choking, laryngospasm) in panic disorder; vivid and recurring dreams and nightmares in posttraumatic stress disorder; anxiety that lasts throughout the day and in the evening in generalized anxiety disorder; depressed mood or anhedonia in major depression; and excessive physical activity and shifting attention in attention deficit hyperactivity disorder.

Medical Disorders

The relative prevalence of medical disorders in insomnia has not been adequately explored.[5] Selected conditions include congestive heart failure (paroxysmal nocturnal dyspnea and orthopnea), chronic obstructive pulmonary disease (COPD) (dyspnea), gastroesophageal reflux disease (GERD) (epigastric pain or burning, laryngospasm, acid taste in mouth, sudden nocturnal awakenings), prostatic hypertrophy (frequent nocturia), and diabetes. The identification of these underlying disorders prior to resorting to symptomatic management of insomnia is critical because insomnia treatments can, in some cases, foment underlying disorders. For example, sedative hypnotic agents can suppress respiration in patients with COPD[6] and increase esophageal acid exposure in those with GERD.[7]

Chronic Pain

Insomnia may occur in the setting of chronic pain. Chronic pain may be caused by rheumatoid arthritis, osteoarthritis, or headache (migraine, cluster, tension type, and paroxysmal hemicrania). In cluster headache, acute episodes tend to occur during rapid eye movement sleep, resulting in sudden awakenings, often with a memory of dreaming just prior to awakening. Other pain conditions include fibromyalgia, which is typically associated with nonrestorative sleep and fatigue along with chronic musculoskeletal pain, early morning stiffness, and specific tender points.[8]

Neurologic Disorders

Dementia from Alzheimer's disease or vascular disease (multi-infarct dementia) can cause multiple awakenings and daytime somnolence. Dementia can also cause a variety of circadian rhythm abnormalities. These may be a result of the central nervous system disturbances that accompany dementia and prolonged bedrest.[9] Other neurologic disorders associated with insomnia include Parkinson's disease and parkinsonian syndromes, Huntington's chorea, progressive dystonia, Tourette's syndrome, and epilepsy.[10]

Sleep Disorders

Sleep disorders include obstructive sleep apnea syndrome, the main symptoms of which are snoring, breathing pauses during sleep, choking, gasping, morning dry mouth, and headaches.[11] Symptoms of restless legs syndrome include an irresistible urge to move the extremities, limb paresthesia, onset of symptoms during period of rest and in the evening or at bedtime, and relief of symptoms with movement. Periodic limb movement disorder is thought to be etiologically related to restless legs syndrome, but patients typically present with only insomnia or report, in addition, twitching and repetitive movements of the extremities during sleep or just prior to falling asleep. The disorder is established by polysomnography, whereas polysomnographic testing is not required for the diagnosis of restless legs syndrome .[11]

Circadian Rhythm Sleep Disorders

Circadian rhythm sleep disorders feature a disturbance in the coordination between internal and environmental circadian rhythms.[11] Insomnia is one of the core symptoms of these disorders. Time zone change (jet lag) syndrome is caused by rapid travel across time zones. Eastward travel is more problematic than westward travel and travel across more than 2 to 3 time zones surpasses the adaptive capabilities of the body. Shift work sleep disorder results from a change in work shifts and corresponding changes in sleep/wake schedules, resulting in poor sleep quality immediately following the new shift. The severity of symptoms is proportional to the frequency with which shifts are changed, the magnitude of each change, as well as the frequency of counterclockwise (phase-advancing) changes. However, even workers engaged in fixed shifts experience difficulties in sleep since they change their sleep schedule for social reasons and are often forced to sleep during the day, when daytime noise and light can interfere with sleep quality. In delayed sleep phase syndrome, individuals fall asleep later than normal evening bedtime hours and awaken later than desired, often extending their bedtimes well into the afternoon. The disorder is most common in adolescents and young adults. In advanced sleep phase syndrome, sleep/wake times are advanced in relationship to socially desired schedules. The disorder is more common in the elderly.


A partial list of those medications with insomnia as a side effect appears in the table below.[12]

Table. Prescription Medications With Insomnia Side Effects

Anti-arrhythmic Quinidine
Antidepressants Fluoxetine
Antiepileptic Phenytoin
Antihypertensives Clonidine
Anti-inflammatories Steroids
Antiparkinsonian Levodopa
Bronchodilator Theophylline
Diuretic Triamterene
Hormones Synthroid (thyroid hormone)
Medications with sedating effects, such as sedative-hypnotics, can be associated with insomnia following rapid discontinuation.

Evaluation and Management Guidelines

Given the extent to which insomnia is associated with other conditions, patients presenting with the chief complaint of insomnia should be carefully evaluated for the presence of comorbid disorders. Whenever possible, comorbid disorders should be managed by their specific treatments prior to resorting to symptomatic management of the insomnia itself. Examples include:

  • Antidepressants and psychotherapy for mood and anxiety disorders;
  • Supervised drug withdrawal and cognitive behavioral therapy for substance use disorders;
  • Oxygen, beta-2 agonists, and nasal steroids for COPD;
  • Proton pump inhibitors and dietary changes for GERD;
  • Nonsteroidal anti-inflammatory agents and opioids for chronic pain;
  • Continuous positive airway pressure and oral appliances for obstructive sleep apnea syndrome;
  • Dopaminergic agents for restless legs syndrome; and
  • Phototherapy and sleep schedule alterations for circadian rhythm sleep disorders.

Nevertheless, management of the comorbid condition does not guarantee the dissipation of insomnia. For example, 44% of patients with major depression continue to experience disturbed sleep after effective management of the depressive disorder .[13] The potential reasons for persistent insomnia include

  • Incomplete resolution of the comorbid disorder;
  • Treatments of comorbid disorders themselves can cause insomnia (see Table above);
  • Insomnia may be caused by another unidentified disorder; and
  • Coexistence of a primary insomnia disorder.

Therefore, independent management of insomnia is often necessary for the complete resolution of the patient's complaints. Measures that have proven effective in comorbid insomnia include cognitive behavioral therapy[14] and the use of pharmacologic agents. Readers are referred to the companion Medscape article entitled "Insomnia and Comorbid Chronic Obstructive Pulmonary Disease" for a detailed description of both of these treatment measures.

This activity is supported by an independent educational grant from Takeda Pharmaceuticals North America, Inc.



  1. National Institutes of Health. National Institutes of Health State of the Science Conference statement on manifestations and management of chronic insomnia in adults, June 13-15, 2005. Sleep. 2005;28:1049-1057. Abstract
  2. Buysse DJ, Germaine A, Moul D, Nofzinger EA. Insomnia. In: Buysse DJ, ed. Sleep Disorders and Psychiatry. Arlington, Va: American Psychiatric Publishing, Inc; 2005:31-84.
  3. Buysse DJ, Reynolds CF 3rd, Kupfer DJ, et al. Clinical diagnoses in 216 insomnia patients using the International Classification of Sleep Disorders (ICSD), DSM-IV and ICD-10 categories: a report from the APA/NIMH DSM-IV field trial. Sleep. 1994;17:630-637. Abstract
  4. Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders. An opportunity for prevention? JAMA. 1989;262:1479-1484. Abstract
  5. Katz DA, McHorney CA. Clinical correlates of insomnia in patients with chronic illness. Arch Intern Med. 1998;158:1099-1107. Abstract
  6. Stege G, Vos PJ, van den Elshout FJ, et al. Sleep, hypnotics and chronic obstructive pulmonary disease. Respir Med. 2008;102:801-814. Abstract
  7. Shah AP, Cohen S, Kwok K, et al. Hypnotic medications impair nocturnal esophageal acid clearance: a double blind, placebo controlled study using simultaneous pH testing and polysomnography. Programs and abstracts presented at the Annual Digestive Diseases Week meeting; May 22, 2006; Los Angeles, California.
  8. Menefee LA, Cohen MJMC, Anderson WR, Doghramji K, Frank ED, Lee H. Sleep disturbance and nonmalignant chronic pain: a comprehensive review of the literature. Pain Med. 2000;1:156-172. Abstract
  9. Motohashi Y, Maeda A, Wakamatsu H, Higuchi S, Yuasa T. Circadian rhythm abnormalities of wrist activity of institutionalized dependent elderly persons with dementia. J Gerontol A Biol Sci Med Sci. 2000;55:M740-M743. Abstract
  10. Provini F, Lombardi C, Lugaresi E. Insomnia in neurological disease. Semin Neurol. 2005;25:81-89. Abstract
  11. American Academy of Sleep Medicine (2005). The International Classification of Sleep Disorders, Second Edition (ICSD-2): Diagnostic and Coding Manual. Westchester, Ill: American Academy of Sleep Medicine; 2005.
  12. McCrae CS, Lichstein KL. Secondary insomnia: Diagnostic challenges and intervention opportunities. Sleep Med Rev. 2001;5:47-61. Abstract
  13. Nierenberg AA, Keefe BR, Leslie VC, et al. Residual symptoms in depressed patients who respond acutely to fluoxetine. J Clin Psychiatry. 1999;60:221-225. Abstract
  14. Stepanski EJ, Rybarczyk B. Emerging research on the treatment and etiology of secondary or comorbid insomnia. Sleep Med Rev. 2006;10:7-18. Abstract