Jump to content

Insomnia: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
No edit summary
Undid revision 283097887 by Bsscully2 (talk)
Line 34: Line 34:


==Causes==
==Causes==
Insomnia can be caused by: BIG BUTTS
Insomnia can be caused by:
*[[Psychoactive drug]]s or [[stimulant]]s, including certain [[medications]], [[herbs]], [[caffeine]], [[cocaine]], [[ephedrine]], [[amphetamine]]s, [[methylphenidate]], [[MDMA]], [[methamphetamine]] and [[modafinil]]
*[[Psychoactive drug]]s or [[stimulant]]s, including certain [[medications]], [[herbs]], [[caffeine]], [[cocaine]], [[ephedrine]], [[amphetamine]]s, [[methylphenidate]], [[MDMA]], [[methamphetamine]] and [[modafinil]]
*[[Fluoroquinolone]] antibiotic drugs, see [[Fluoroquinolone toxicity]], associated with more severe and chronic types of insomnia <ref>{{cite journal |author=Lawrence KR, Adra M, Keir C |title=Hypoglycemia-induced anoxic brain injury possibly associated with levofloxacin |journal=J. Infect. |volume=52 |issue=6 |pages=e177–80 |year=2006 |month=June |pmid=16269178 |doi=10.1016/j.jinf.2005.08.024 |url=}}</ref>
*[[Fluoroquinolone]] antibiotic drugs, see [[Fluoroquinolone toxicity]], associated with more severe and chronic types of insomnia <ref>{{cite journal |author=Lawrence KR, Adra M, Keir C |title=Hypoglycemia-induced anoxic brain injury possibly associated with levofloxacin |journal=J. Infect. |volume=52 |issue=6 |pages=e177–80 |year=2006 |month=June |pmid=16269178 |doi=10.1016/j.jinf.2005.08.024 |url=}}</ref>

Revision as of 02:00, 11 April 2009

This article is about the sleeping disorder. For other uses, see Insomnia (disambiguation).
Insomnia
SpecialtyNeurology, psychiatry, neuroscience, psychology Edit this on Wikidata

Insomnia is a symptom[1] of a sleeping disorder characterized by persistent difficulty falling asleep or staying asleep despite the opportunity. Insomnia is a symptom, not a stand-alone diagnosis or a disease. By definition, insomnia is "difficulty initiating or maintaining sleep, or both" and it may be due to inadequate quality or quantity of sleep. It is typically followed by functional impairment while awake. Insomniacs have been known to complain about being unable to close their eyes or "rest their mind" for more than a few minutes at a time. Both organic and non-organic insomnia constitute a sleep disorder.[2]

According to the U.S. Department of Health and Human Services in year 2007, approximately 64 million Americans suffer from insomnia on a regular basis each year.[3] Insomnia is 1.4 times more common in women than in men.[4]

Types of insomnia

Although there are several different degrees of insomnia, three types of insomnia have been clearly identified: transient, acute, and chronic.

  1. Transient insomnia lasts from days to weeks. 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.[5]
  2. Acute insomnia is the inability to consistently sleep well for a period of between three weeks to six months.[6]
  3. Chronic insomnia lasts for years at a time. It can be caused by another disorder, or it can be a primary disorder. Its effects can vary according to its causes. They might include sleepiness, muscular fatigue, hallucinations, and/or mental fatigue; but people with chronic insomnia often show increased alertness. Some people that live with this disorder see things as though they were happening in slow motion, whereas moving objects seem to blend together. Can cause double vision.[5]

Patterns of insomnia

The pattern of insomnia often is related to the etiology.[7] Insomnia affects 8 in 10 people.

  1. Onset insomnia - difficulty falling asleep at the beginning of the night, often associated with anxiety disorders.
  2. Middle-of-the-Night Insomnia - Insomnia characterized by difficulty returning to sleep after awakening in the middle of the night or waking too early in the morning. Also referred to as nocturnal awakenings. Encompasses middle and terminal insomnia.
  3. Middle insomnia - waking during the middle of the night, difficulty maintaining sleep. Often associated with pain disorders or medical illness.
  4. Terminal (or late) insomnia - early morning waking. Characteristic of clinical depression.

Causes

Insomnia can be caused by:

A common misperception is that the amount of sleep a person requires decreases as he or she 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.[11]

An overactive mind or physical pain may also be causes. Finding the underlying cause of insomnia is usually necessary to cure it. Insomnia can be common after the loss of a loved one, even years or decades after the death, if they have not gone through the grieving process. Overall, symptoms and the degree of their severity affect each individual differently depending on their mental health, physical condition, and attitude or personality.

Epidemiology

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.[12] 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 2003 poll of adults between the ages of 55 and 84.[12]

Diagnosis

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 insomnia. If a patient has trouble getting to sleep, but has normal sleep pattern once asleep, a circadian rhythm disorder is a likely cause.

Sleep duration and mortality

A survey of 1.1 million residents in America found that those who reported sleeping 7.5 hours or more had an increased rate of mortality whereas those who slept 6 hours or less had a reduced mortality ratio. Getting 8.5 or more hours of sleep per night increases the mortality rate by 15%. Severe insomnia - sleeping less than 3.5 hours in women and 4.5 hours in men - leads to a 15% increase in mortality. However, most of the increase in mortality from severe insomnia was discounted after controlling for comorbid disorders. After controlling for sleep duration and insomnia, use of sleeping pills was also found to be associated with an increased mortality rate. 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 may actually increase longevity and severe insomnia has only a very small effect on mortality. 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. It is unclear why sleeping longer than 7.5 hours is associated with excess mortality.[13]

Insomnia versus poor sleep quality

Poor sleep quality can occur as a result of sleep apnea or clinical depression. Poor sleep quality is caused by the individual not reaching stage 4 or delta sleep which has restorative properties. There are, however, people who are unable to achieve stage 4 sleep due to brain damage who lead perfectly normal lives.

Sleep apnea is a condition that occurs when a sleeping person's breathing is interrupted, thus interrupting the normal sleep cycle. With the obstructive form of the condition, some part of the sleeper's respiratory tract loses muscle tone and partially collapses. People with obstructive sleep apnea often do not remember awakening or having difficulty breathing, but they complain of excessive sleepiness during the day. Central sleep apnea interrupts the normal breathing stimulus of the central nervous system, and the individual must actually wake up to resume breathing. This form of apnea is often related to a cerebral vascular condition, congestive heart failure, and premature aging.

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.[14]

Treatment for insomnia

In many cases, insomnia is caused by another disease, side effects from medications or a psychological problem. It is important to identify or rule out medical and psychological before deciding on the treatment for the insomnia.[15] Attention to sleep hygiene is an important first line treatment strategy and should be tried before any pharmacological approach is considered.[16]

Non-pharmacological strategies

Non-pharmacological strategies are superior to hypnotic medication for insomnia because tolerance develops to the hypnotic effects as well as dependence can develop with rebound withdrawal effects developing upon discontinuation. Hypnotic medication is therefore only recommended for short term use. Non pharmacological strategies however, have long lasting improvements to insomnia and are recommended as a first line and long term strategie of managing insomnia. The strategies include attention to sleep hygiene, stimulus control, behavioral interventions, sleep-restriction therapy, patient education and relaxation therapy.[17]

Cognitive behavior therapy

A recent study found that cognitive behavior therapy is more effective than hypnotic medications in controlling insomnia. In this therapy, patients are taught improved sleep habits and relieved of counter-productive assumptions about sleep. 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 cognitive behavior therapy have sustained and lasting effects on treating insomnia long after therapy has been discontinued.[18][19] The addition of hypnotic medications with CBT adds no benefit in insomnia. The long lasting benefits of a course of CBT shows superiority over pharmacological hypnotic drugs. Even in the short term when compared to short term hypnotic medication such as zolpidem (Ambien), CBT still shows significant superiority. Thus CBT is recommended as a first line treatment for insomnia.[20]

Medications

Many insomniacs rely on sleeping tablets and other sedatives to get rest. All sedative drugs have the potential of causing psychological dependence where the individual cannot psychologically accept that they can sleep without drugs [citation needed]. 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 titrated 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.[21]

In comparing the options, a systematic review found that benzodiazepines and nonbenzodiazepines have similar efficacy which was not significantly more than for antidepressants.[22] Benzodiazepines did not have a significant tendency for more adverse drug reactions.[22] Chronic users of hypnotic medications for insomnia do not have better sleep than chronic insomniacs who do not take medications. In fact, chronic users of hypnotic medications actually have more regular nighttime awakenings than insomniacs who do not take hypnotic medications.[23] A further review of the literature regarding benzodiazepine hypnotic as well as the nonbenzodiazepines concluded that these drugs caused 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. Preferably hypnotics should be prescribed for only a few days at the lowest effective dose and avoided altogether wherever possible in the elderly.[24]

Benzodiazepines

Main article: Benzodiazepine

The most commonly used class of hypnotics prescribed for insomnia are the benzodiazepines. Benzodiazepines bind unselectively to the GABAA receptor.[22] These include drugs such as temazepam, 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 whilst decreasing time spent in deep sleep such as REM sleep.[25] A further problem is with regular use of short acting sleep aids for insomnia, day time rebound anxiety can emerge.[26]

Non-benzodiazepines

Main article: Nonbenzodiazepine

Nonbenzodiazepine sedative-hypnotic drugs, such as zolpidem, zaleplon, zopiclone and eszopiclone, are a newer classification of hypnotic medications. They work on the benzodiazepine site on the GABAA receptor complex similarly to the benzodiazepine class of drugs. Some but not all of the nonbenzodiazepines are selective for the α1 subunit on GABAA receptors which is responsible for inducing sleep and may therefore have a cleaner side effect profile than the older benzodiazepines. Zopiclone and eszopiclone like benzodiazepine drugs bind unselectively to α1, α2, α3 and α5 GABAA benzodiazepine receptors.[27] Zolpidem is more selective and zaleplon is highly selective for the α1 subunit thus giving them an advantage over benzodiazepines in terms of sleep architecture and a reduction in side effects.[28][29] However, there are controversies over whether these non-benzodiazepine drugs are superior to benzodiazepines. These drugs appear to cause both psychological dependence and physical dependence though less than traditional benzodiazepines and can also cause the same memory and cognitive disturbances along with morning sedation.

Antidepressants

Main article: Antidepressants

Some antidepressants such as amitriptyline, doxepin, mirtazapine, and trazodone can often have a very strong sedative effect, and are prescribed off label to treat insomnia. [30] The major drawback of these drugs is that they have antihistaminergic, anticholinergic and antiadrenergic properties which can lead to many side effects. Some also alter sleep architecture. As with many benzodiazepines, the use of antidepressants in the treatment of insomnia can lead to physical dependence; withdrawal may induce rebound insomnia and actually further complicate matters in the long-term.

Mirtazapine is known to decrease sleep latency, promoting sleep effiency and increasing the total amount of sleeping time in patients suffering from both depression and insomnia [31] [32]

Melatonin and melatonin agonists

The hormone and supplement melatonin is effective in several types of insomnia. Melatonin has demonstrated effectiveness equivalent to the prescription sleeping tablet zopiclone in inducing sleep and regulating the sleep/waking cycle.[33] One particular benefit of melatonin is that it can treat insomnia without altering the sleep pattern which is altered by many prescription sleeping tablets. Another benefit is it does not impair performance related skills.[34][35]

Melatonin agonists, including ramelteon (Rozerem) and tasimelteon, seem to lack the potential for abuse and dependence. This class of drugs has a relatively mild side effect profile and lower likelihood of causing morning sedation. While these drugs show good effects for the treatment of insomnia due to jet lag,[36] the results for other forms of insomnia are less promising.[37]

Natural substances such as 5-HTP and L-Tryptophan have been said to fortify the serotonin-melatonin pathway and aid people with various sleep disorders including insomnia.[38]

Antihistamines

The antihistamine diphenhydramine is widely used in nonprescription sleep aids such as Tylenol PM®, with a 50 mg recommended dose mandated by the FDA. In the United Kingdom, Australia, New Zealand, South Africa, and other countries, a 25 mg to 50 mg recommended dose is permitted. While it is available over the counter, 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. Dependence does not seem to be an issue with this class of drugs.

Cyproheptadine is a useful alternative to benzodiazepine hypnotics in the treatment of insomnia. Cyproheptadine may be superior to benzodiazepines in the treatment of insomnia because cyproheptadine enhances sleep quality and quantity whereas benzodiazepines tend to decrease sleep quality.[39]

Atypical antipsychotics

Low doses of certain atypical antipsychotics such as quetiapine, olanzapine and risperidone are also prescribed for their sedative effect but the danger of neurological and cognitive side effects make these drugs a poor choice to treat insomnia. Over time, quetiapine may lose its effectiveness as a sedative. The ability of quetiapine to produce sedation is determined by the dosage. Higher doses (300 mg - 900 mg) are usually taken for its use as an antipsychotic, while lower doses (25 mg - 200 mg) have a marked sedative effect, e.g. if a patient takes 300 mg, he/she will more likely benefit from the drug's antipsychotic effects, but if the dose is brought down to 100 mg, it will leave the patient feeling more sedated than at 300 mg, because it primarily works as a sedative at lower doses.

Eplivanserin is an investigational drug with a mechanism similar to these antipsychotics, but probably with less side effects.

Other substances

Some insomniacs use herbs such as valerian, chamomile, lavender, hops, and passion-flower. Valerian has undergone multiple studies and appears to be modestly effective.[40][41][42] Cannabis has also been proven as an effective treatment for insomnia. [43]

Middle-of-the-night awakenings due to polyuria or other effects from alcohol consumption are common, and hangovers can also lead to morning grogginess.

Insomnia may be a symptom of magnesium deficiency, or low magnesium levels, but this has not yet been proven. A healthy diet containing magnesium, can help to improve sleep in individuals without an adequate intake of magnesium.[44]

Other reports cite the use of an elixir of cider vinegar and honey but the evidence for this is only anecdotal.[45]

Sexual activity

In several cases, sexual intercourse has been found to heavily reduce stress patterns. Although in many cases stress is not the cause of insomnia.

See also

References

  1. ^ Rowley, James A. (September 7, 2005). "Insomnia". eMedicine from WebMD. Retrieved 2008-08-04. That insomnia is a symptom, not a disease, is important to note; ... {{cite web}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  2. ^ "WHO technical meeting on sleep and health" (pdf). Retrieved 2009-01-25. "Dyssomnias" (pdf). WHO. pp. 7–11. Retrieved 2009-01-25.
  3. ^ "Brain Basics: Understanding Sleep: National Institute of Neurological Disorders and Stroke (NINDS)". Retrieved 2007-12-16.
  4. ^ "Several Sleep Disorders Reflect Gender Differences". Retrieved 2008-09-05.
  5. ^ a b Roth, Thomas (2004-02-25). "Insomnia: Epidemiology, characteristics, and consequences". Clinical Cornerstone. 5 (3): 5–15. doi:10.1016/S1098-3597(03)90031-7. {{cite journal}}: |access-date= requires |url= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  6. ^ "Insomnia - sleeplessness, chronic insomnia, acute insomnia, mental ..." driectoryM articles. Retrieved 2008-04-29.
  7. ^ eMedicine - Sleep Disorders : Article by Curley L Bonds, MD
  8. ^ Lawrence KR, Adra M, Keir C (2006). "Hypoglycemia-induced anoxic brain injury possibly associated with levofloxacin". J. Infect. 52 (6): e177–80. doi:10.1016/j.jinf.2005.08.024. PMID 16269178. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ Douma, S.L, Husband, C., O’Donnell, M.E., Barwin, B.N., Woodend A.K. (2005). "Estrogen-related Mood Disorders Reproductive Life Cycle Factors". Advances in Nursing Science. 28 (4): 364–375. PMID 16292022.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ^ Lasiuk, GC and Hegadoren, KM (2007). "The Effects of Estradiol on Central Serotonergic Systems and Its Relationship to Mood in Women". Biological Research for Nursing (2007),. 9 (2): 147–160. doi:10.1177/1099800407305600. PMID 17909167.{{cite journal}}: CS1 maint: extra punctuation (link) CS1 maint: multiple names: authors list (link)
  11. ^ American Family Physician: Chronic Insomnia: A Practical Review
  12. ^ a b "2002 Sleep in America Poll". National Sleep Foundation. Retrieved 2008-08-13.
  13. ^ Kripke DF, Garfinkel L, Wingard DL, Klauber MR, Marler MR (2002). "Mortality associated with sleep duration and insomnia". Arch. Gen. Psychiatry. 59 (2): 131–6. PMID 11825133. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  14. ^ Sleep issues in Parkinson’s disease. Neurology. 2005. pp. 64, S12–20. {{cite book}}: Unknown parameter |accessmonth= ignored (|access-date= suggested) (help); Unknown parameter |accessyear= ignored (|access-date= suggested) (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  15. ^ Wortelboer U, Cohrs S, Rodenbeck A, Rüther E (2002). "Tolerability of hypnosedatives in older patients". Drugs Aging. 19 (7): 529–39. doi:10.2165/00002512-200219070-00006. PMID 12182689.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ^ Flamer HE (1995). "Sleep problems". Med. J. Aust. 162 (11): 603–7. PMID 7791648. {{cite journal}}: Unknown parameter |month= ignored (help)
  17. ^ Kirkwood CK (1999). "Management of insomnia". J Am Pharm Assoc. 39 (5): 688–96, quiz 713–4. PMID 10533351.
  18. ^ Jacobs, Gregg (September 27, 2004). "Cognitive Behavior Therapy and Pharmacotherapy for Insomnia: A Randomized Controlled Trial and Direct Comparison". Archives of Internal Medicine. 164 (17): 1888–1896. doi:10.1001/archinte.164.17.1888. PMID 15451764. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  19. ^ Morin, C. M. (1999). "Behavioral and Pharmacological Therapies for Late-Life Insomnia: A Randomized Controlled Trial". JAMA the Journal of the American Medical Association. 281: 991. doi:10.1001/jama.281.11.991. PMID 10086433.
  20. ^ KARL E. MILLER, M.D. (2005). "Cognitive Behavior Therapy vs. Pharmacotherapy for Insomnia". American Family Physician. {{cite journal}}: Unknown parameter |month= ignored (help)
  21. ^ Glass J, Lanctôt KL, Herrmann N, Sproule BA, Busto UE (2005). "Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits". BMJ. 331 (7526): 1169. doi:10.1136/bmj.38623.768588.47. PMC 1285093. PMID 16284208. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  22. ^ a b c Buscemi N, Vandermeer B, Friesen C, Bialy L, Tubman M, Ospina M, Klassen TP, Witmans M. (2007). "The efficacy and safety of drug treatments for chronic insomnia in adults: a meta-analysis of RCTs". J Gen Intern Med. 22 (9): 1335–1350. doi:10.1007/s11606-007-0251-z. PMID 17619935. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  23. ^ Ohayon MM, Caulet M (1995). "Insomnia and psychotropic drug consumption". Prog. Neuropsychopharmacol. Biol. Psychiatry. 19 (3): 421–31. doi:10.1016/0278-5846(94)00023-B. PMID 7624493. {{cite journal}}: Unknown parameter |month= ignored (help)
  24. ^ "What's wrong with prescribing hypnotics?". Drug Ther Bull. 42 (12): 89–93. 2004. doi:10.1136/dtb.2004.421289. PMID 15587763. {{cite journal}}: Unknown parameter |month= ignored (help)
  25. ^ Tsoi, Wf (1991). "Insomnia: drug treatment". Annals of the Academy of Medicine, Singapore. 20 (2): 269–72. ISSN 0304-4602. PMID 1679317. {{cite journal}}: Unknown parameter |month= ignored (help)
  26. ^ Montplaisir J (2000). "Treatment of primary insomnia" (PDF). CMAJ. 163 (4): 389–91. PMC 80369. PMID 10976252. {{cite journal}}: Unknown parameter |month= ignored (help)
  27. ^ WHO (2006). "World Health Organisation - Assessment of Zopiclone" (PDF). who.int.
  28. ^ Rowlett JK, Woolverton WL (1996). "Assessment of benzodiazepine receptor heterogeneity in vivo: apparent pA2 and pKB analyses from behavioral studies" (PDF). Psychopharmacology (Berl.). 128 (1): 1–16. doi:10.1007/s002130050103. PMID 8944400. {{cite journal}}: Unknown parameter |month= ignored (help)
  29. ^ Noguchi H (2004). "Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats" (pdf). J Pharmacol Sci. 94 (3): 246–51. doi:10.1254/jphs.94.246. PMID 15037809. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  30. ^ Bertschy G, Ragama-Pardos E, Muscionico M; et al. (2005). "Trazodone addition for insomnia in venlafaxine-treated, depressed inpatients: a semi-naturalistic study". Pharmacol. Res. 51 (1): 79–84. doi:10.1016/j.phrs.2004.06.007. PMID 15519538. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  31. ^ Winokur A, DeMartinis NA 3rd, McNally DP, Gary EM, Cormier JL, Gary KA. ; et al. "Comparative effects of mirtazapine and fluoxetine on sleep physiology measures in patients with major depression and insomnia". J Clin Psychiatry year=2003. {{cite journal}}: Explicit use of et al. in: |author= (help); Missing pipe in: |journal= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
  32. ^ Schittecatte M, Dumont F, Machowski R, Cornil C, Lavergne F, Wilmotte J ; et al. "Effects of mirtazapine on sleep polygraphic variables in major depression". Neuropsychobiology year=2002 url=http://www.ncbi.nlm.nih.gov/pubmed/12566938?ordinalpos=62&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum. {{cite journal}}: Explicit use of et al. in: |author= (help); Missing pipe in: |journal= (help)CS1 maint: multiple names: authors list (link)
  33. ^ Paul MA, Gray G, Sardana TM, Pigeau RA (2004). "Melatonin and zopiclone as facilitators of early circadian sleep in operational air transport crews". Aviat Space Environ Med. 75 (5): 439–43. PMID 15152897. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  34. ^ Paul MA, Gray G, Kenny G, Pigeau RA (2003). "Impact of melatonin, zaleplon, zopiclone, and temazepam on psychomotor performance". Aviat Space Environ Med. 74 (12): 1263–70. PMID 14692469. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  35. ^ Zhdanova IV, Tucci V (2003). "Melatonin, Circadian Rhythms, and Sleep" ([dead link‍] – Scholar search). Curr Treat Options Neurol. 5 (3): 225–229. doi:10.1007/s11940-003-0013-0. PMID 12670411. {{cite journal}}: External link in |format= (help); Unknown parameter |month= ignored (help)
  36. ^ Rajaratnam, SMW (2 December 2008). "Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials". Lancet. 373: 482. doi:10.1016/S0140-6736(08)61812-7. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  37. ^ Zammit G, Erman M, Wang-Weigand S, Sainati S, Zhang J, Roth T (2007). "Evaluation of the efficacy and safety of ramelteon in subjects with chronic insomnia". J Clin Sleep Med. 3 (5): 495–504. PMC 1978328. PMID 17803013. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  38. ^ Morton Walker, DPM - The Restoration of L-Tryptophan with Its Numerous Physiological Benefits
  39. ^ Tokunaga S (2007). "Effects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats" (pdf). J Pharmacol Sci. 103 (2): 201–6. doi:10.1254/jphs.FP0061173. PMID 17287588. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  40. ^ Donath F, Quispe S, Diefenbach K, Maurer A, Fietze I, Roots I (2000). "Critical evaluation of the effect of valerian extract on sleep structure and sleep quality". Pharmacopsychiatry. 33 (2): 47–53. doi:10.1055/s-2000-7972. PMID 10761819.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  41. ^ Morin CM, Koetter U, Bastien C, Ware JC, Wooten V (2005). "Valerian-hops combination and diphenhydramine for treating insomnia: a randomized placebo-controlled clinical trial". Sleep. 28 (11): 1465–71. PMID 16335333.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  42. ^ Meolie AL, Rosen C, Kristo D; et al. (2005). "Oral nonprescription treatment for insomnia: an evaluation of products with limited evidence". Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 1 (2): 173–87. PMID 17561634. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  43. ^ http://www.cannabis.net/medical-marijuana/pot-docs.html
  44. ^ Hornyak M, Voderholzer U, Hohagen F, Berger M, Riemann D (1998). "Magnesium therapy for periodic leg movements-related insomnia and restless legs syndrome: an open pilot study". Sleep. 21 (5): 501–5. PMID 9703590.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  45. ^ "Cider Vinegar and Insomnia".
Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=Insomnia&oldid=283098261"