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Insomnia

Insomnia
Insomnia Classification and external resources ICD-10 ICD-9 DiseasesDB eMedicine MeSH F51.0, G47.0 307.42, 307.41, 780.51, 780.52 26877 med/2698 D007319

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. Often a characteristic of clinical depression.

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. Both organic and non-organic insomnia constitute a sleep disorder.[2] According to the United States Department of Health and Human Services in year 2007, approximately 64 million Americans regularly suffer from insomnia 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. 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. is the inability to consistently sleep well for a period of between three weeks to six months.[6] 3. 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

Causes
Insomnia can be caused by: • Psychoactive drugs or stimulants, including certain medications, herbs, caffeine, cocaine, ephedrine, amphetamines, methylphenidate, MDMA, methamphetamine and modafinil • Fluoroquinolone antibiotic drugs, see Fluoroquinolone toxicity, associated with more severe and chronic types of insomnia
[8]

• Hormone shifts such as those that precede menstruation and those during menopause • Life problems like fear, stress, anxiety, emotional or mental tension, work problems, financial stress, unsatisfactory sex life

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• Mental disorders such as bipolar disorder, clinical depression, general anxiety disorder, post traumatic stress disorder, schizophrenia, or obsessive compulsive disorder. • Disturbances of the circadian rhythm, such as shift work and jet lag, can cause an inability to sleep at some times of the day and excessive sleepiness at other times of the day. Jet lag is seen in people who travel through multiple time zones, as the time relative to the rising and setting of the sun no longer coincides with the body’s internal concept of it. The insomnia experienced by shift workers is also a circadian rhythm sleep disorder. • Estrogen is considered to play a significant role in women’s mental health (including insomnia). A conceptual model of how estrogen affects mood was suggested by Douma et al. 2005 based on their extensive literature review relating activity of endogenous, bio-identical and synthetic estrogen with mood and wellbeing. They concluded the sudden estrogen withdrawal, fluctuating estrogen, and periods of sustained estrogen low levels correlated with significant mood lowering. Clinical recovery from depression postpartum, perimenopause, and postmenopause was shown to be effective after levels of estrogen were stabilized and/or restored.[9][10] • Certain neurological disorders, brain lesions, or a history of traumatic brain injury • Medical conditions such as hyperthyroidism • Abuse of over-the counter or prescription sleep aids can produce rebound insomnia • Poor sleep hygiene, e.g., noise • Parasomnia, which includes a number of disruptive sleep events including nightmares, sleepwalking, violent behavior while sleeping, and REM behavior disorder, in which a person moves his/her physical body in response to events within his/her dreams • A rare genetic condition can cause a prion-based, permanent and eventually fatal form of insomnia called fatal familial insomnia • Parasites can cause intestinal disturbances while sleeping. A common misperception is that the amount of sleep a person requires decreases as he or

Insomnia
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 misdiagnosed 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 about 7 hours per night had the lowest rates of mortality, whereas those who slept less than 6 hours or more than 8 hours had higher mortality rates. Getting 8.5 or more hours of sleep per night increased the mortality rate

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Insomnia
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.[15]

Potential complications of insomnia.[13] by 15%. Severe insomnia - sleeping less than 3.5 hours in women and 4.5 hours in men also led to a 15% increase in mortality. However, most of the increase in mortality from severe insomnia was discounted after controlling for 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.[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.[16] Attention to sleep hygiene is an important first line treatment strategy and should be tried before any pharmacological approach is considered.[17]

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 strategy of managing insomnia. The strategies include attention to sleep hygiene, stimulus control, behavioral interventions, sleep-restriction therapy, patient education and relaxation therapy.[18]

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

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Insomnia
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.[25]

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.[19][20] 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.[21]

Benzodiazepines
The most commonly used class of hypnotics prescribed for insomnia are the benzodiazepines. Benzodiazepines bind unselectively to the GABAA receptor.[23] 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.[26] A further problem is with regular use of short acting sleep aids for insomnia, day time rebound anxiety can emerge.[27]

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. 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.[22] In comparing the options, a systematic review found that benzodiazepines and nonbenzodiazepines have similar efficacy which was not significantly more than for antidepressants.[23] Benzodiazepines did not have a significant tendency for more adverse drug reactions.[23] 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.[24] A further review of the literature regarding

Non-benzodiazepines
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.[28] 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.[29][30] However, there are controversies over whether these non-benzodiazepine drugs are superior to

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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.

Insomnia

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.[40]

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. [31] 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 [32] [33]

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.

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.[34] 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.[35][36] 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,[37] the results for other forms of insomnia are less promising.[38] 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.[39]

Other substances
Some insomniacs use herbs such as valerian, chamomile, lavender, hops, and passionflower. Valerian has undergone multiple studies and appears to be modestly effective.[41][42][43] Cannabis has also been proven as an effective treatment for insomnia. [44]

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From Wikipedia, the free encyclopedia
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.[45] Other reports cite the use of an elixir of cider vinegar and honey but the evidence for this is only anecdotal.[46]

Insomnia
[4] "Several Sleep Disorders Reflect Gender Differences". http://pn.psychiatryonline.org/cgi/ content/full/42/10/40. Retrieved on 2008-09-05. [5] ^ Roth, Thomas; Timothy Roehrs (2004-02-25). "Insomnia: Epidemiology, characteristics, and consequences". Clinical Cornerstone 5 (3): 5–15. doi:10.1016/S1098-3597(03)90031-7. [6] "Insomnia - sleeplessness, chronic insomnia, acute insomnia, mental ...". driectoryM articles. http://articles.directorym.com/Insomniaa352.html. Retrieved on 2008-04-29. [7] eMedicine - Sleep Disorders : Article by Curley L Bonds, MD [8] Lawrence KR, Adra M, Keir C (June 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. [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. [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. [11] American Family Physician: Chronic Insomnia: A Practical Review [12] ^ "2002 Sleep in America Poll". National Sleep Foundation. http://www.sleepfoundation.org/site/ c.huIXKjM0IxF/b.2417355/k.143E/ 2002_Sleep_in_America_Poll.htm. Retrieved on 2008-08-13. [13] Mayo Clinic > Insomnia > Complications By Mayo Clinic staff. Retrieved on May, 5, 2009 [14] Kripke DF, Garfinkel L, Wingard DL, Klauber MR, Marler MR (February 2002). "Mortality associated with sleep duration and insomnia". Arch. Gen. Psychiatry 59 (2): 131–6. PMID 11825133. http://archpsyc.ama-assn.org/ cgi/content/full/59/2/131. [15] Sleep issues in Parkinson’s disease. Neurology. 2005. pp. 64; S12–20.

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
• • • • • • • Sleep Sleep disorder Fatal familial insomnia Sleep deprivation Delayed sleep phase syndrome Actigraphy Thai Ngoc

References
[1] Rowley, James A.; Nicholas Lorenzo (September 7, 2005). "Insomnia". eMedicine from WebMD. http://www.emedicine.com/neuro/ TOPIC418.HTM#target10. Retrieved on 2008-08-04. "That insomnia is a symptom, not a disease, is important to note; ..." [2] "WHO technical meeting on sleep and health" (pdf). http://www.euro.who.int/ document/E84683_1.pdf. Retrieved on 2009-01-25. "Dyssomnias" (pdf). WHO. 7-11. http://www.who.int/ selection_medicines/committees/expert/ 17/application/Section24_GAD.pdf. Retrieved on 2009-01-25. [3] "Brain Basics: Understanding Sleep: National Institute of Neurological Disorders and Stroke (NINDS)". http://www.ninds.nih.gov/disorders/ brain_basics/understanding_sleep.htm. Retrieved on 2007-12-16.

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http://www.neurology.org/cgi/content/ (9): 1335–1350. doi:10.1007/ full/64/12_suppl_3/S12. s11606-007-0251-z. PMID 17619935. [16] Wortelboer U, Cohrs S, Rodenbeck A, [24] Ohayon MM, Caulet M (May 1995). Rüther E (2002). "Tolerability of "Insomnia and psychotropic drug hypnosedatives in older patients". Drugs consumption". Prog. Neuropsychopharmacol. Biol. Psychiatry Aging 19 (7): 529–39. doi:10.2165/ 00002512-200219070-00006. PMID 19 (3): 421–31. doi:10.1016/ 12182689. 0278-5846(94)00023-B. PMID 7624493. [17] Flamer HE (June 1995). "Sleep http://linkinghub.elsevier.com/retrieve/ pii/027858469400023B. problems". Med. J. Aust. 162 (11): [25] "What’s wrong with prescribing 603–7. PMID 7791648. [18] Kirkwood CK (1999). "Management of hypnotics?". Drug Ther Bull 42 (12): 89–93. December 2004. doi:10.1136/ insomnia". J Am Pharm Assoc 39 (5): dtb.2004.421289. PMID 15587763. 688–96; quiz 713–4. PMID 10533351. http://www.nelm.nhs.uk/en/NeLM-Area/ [19] Jacobs, Gregg; Edward F. Pace-Schott, Evidence/Drug-Class-Focused-Reviews/ Robert Stickgold, Michael W. Otto 498264/. (September 27, 2004). "Cognitive [26] Tsoi, Wf (Mar 1991). "Insomnia: drug Behavior Therapy and Pharmacotherapy treatment.". Annals of the Academy of for Insomnia: A Randomized Controlled Trial and Direct Comparison". Archives Medicine, Singapore 20 (2): 269–72. ISSN 0304-4602. PMID 1679317. of Internal Medicine 164 (17): [27] Montplaisir J (August 2000). "Treatment 1888–1896. doi:10.1001/ archinte.164.17.1888. PMID 15451764. of primary insomnia" (PDF). CMAJ 163 http://archinte.ama-assn.org/cgi/content/ (4): 389–91. PMID 10976252. PMC: full/164/17/ 80369. 1888?ijkey=6a2af558a671b089d7c77db5fc5f53a450fd1cda. http://www.pubmedcentral.nih.gov/ [20] Morin, C. M. (1999). "Behavioral and articlerender.fcgi?tool=pubmed&pubmedid=109762 Pharmacological Therapies for Late-Life [28] WHO (2006). "World Health Insomnia: A Randomized Controlled Organisation - Assessment of Zopiclone" Trial". JAMA the Journal of the American (PDF). who.int. http://www.who.int/ medicines/areas/quality_safety/ Medical Association 281: 991. 4.6ZopicloneCritReview.pdf. doi:10.1001/jama.281.11.991. PMID [29] Rowlett JK, Woolverton WL (November 10086433. http://jama.ama-assn.org/cgi/ 1996). "Assessment of benzodiazepine content/full/281/11/991. receptor heterogeneity in vivo: apparent [21] KARL E. MILLER, M.D. (July 2005). pA2 and pKB analyses from behavioral "Cognitive Behavior Therapy vs. studies". Psychopharmacology (Berl.) Pharmacotherapy for Insomnia". American Family Physician. 128 (1): 1–16. doi:10.1007/ http://www.aafp.org/afp/20050715/tips/ s002130050103. PMID 8944400. 7.html. http://www.springerlink.com/content/ [22] Glass J, Lanctôt KL, Herrmann N, xeu44evyanvw1n65/fulltext.pdf. Sproule BA, Busto UE (November 2005). [30] Noguchi H; Kitazumi K, Mori M, Shiba T. "Sedative hypnotics in older people with (March 2004). "Electroencephalographic insomnia: meta-analysis of risks and properties of zaleplon, a nonbenzodiazepine sedative/hypnotic, in benefits". BMJ 331 (7526): 1169. doi:10.1136/bmj.38623.768588.47. PMID rats" (pdf). J Pharmacol Sci. 94 (3): 16284208. PMC: 1285093. 246–51. doi:10.1254/jphs.94.246. PMID http://www.bmj.com/cgi/content/full/331/ 15037809. http://www.jstage.jst.go.jp/ 7526/1169. article/jphs/94/3/246/_pdf. [23] ^ Buscemi N, Vandermeer B, Friesen C, [31] Bertschy G, Ragama-Pardos E, Bialy L, Tubman M, Ospina M, Klassen Muscionico M, et al (January 2005). TP, Witmans M. (September 2007). "The "Trazodone addition for insomnia in efficacy and safety of drug treatments venlafaxine-treated, depressed for chronic insomnia in adults: a metainpatients: a semi-naturalistic study". analysis of RCTs". J Gen Intern Med 22 Pharmacol. Res. 51 (1): 79–84.

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doi:10.1016/j.phrs.2004.06.007. PMID ramelteon in subjects with chronic 15519538. insomnia". J Clin Sleep Med 3 (5): [32] Winokur A, DeMartinis NA 3rd, McNally 495–504. PMID 17803013. DP, Gary EM, Cormier JL, Gary KA. , et [39] Morton Walker, DPM - The Restoration al (August of L-Tryptophan with Its Numerous url=http://www.ncbi.nlm.nih.gov/ Physiological Benefits pubmed/ [40] Tokunaga S; Takeda Y, Shinomiya K, 14658972?ordinalpos=30&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_Def Hirase M, Kamei C. (February 2007). effects of mirtazapine and fluoxetine on "Effects of some H1-antagonists on the sleep physiology measures in patients sleep-wake cycle in sleep-disturbed rats" with major depression and insomnia". J (pdf). J Pharmacol Sci. 103 (2): 201–6. Clin Psychiatry year=2003. doi:10.1254/jphs.FP0061173. PMID [33] Schittecatte M, Dumont F, Machowski R, 17287588. http://www.jstage.jst.go.jp/ Cornil C, Lavergne F, Wilmotte J , et al. article/jphs/103/2/201/_pdf. "Effects of mirtazapine on sleep [41] Donath F, Quispe S, Diefenbach K, polygraphic variables in major Maurer A, Fietze I, Roots I (2000). depression". Neuropsychobiology "Critical evaluation of the effect of year=2002 valerian extract on sleep structure and url=http://www.ncbi.nlm.nih.gov/ sleep quality". Pharmacopsychiatry 33 pubmed/ (2): 47–53. doi:10.1055/s-2000-7972. 12566938?ordinalpos=62&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_Def PMID 10761819. [34] Paul MA, Gray G, Sardana TM, Pigeau [42] Morin CM, Koetter U, Bastien C, Ware RA (May 2004). "Melatonin and JC, Wooten V (2005). "Valerian-hops zopiclone as facilitators of early combination and diphenhydramine for circadian sleep in operational air treating insomnia: a randomized placebotransport crews". Aviat Space Environ controlled clinical trial". Sleep 28 (11): Med 75 (5): 439–43. PMID 15152897. 1465–71. PMID 16335333. [35] Paul MA, Gray G, Kenny G, Pigeau RA [43] Meolie AL, Rosen C, Kristo D, et al (December 2003). "Impact of melatonin, (2005). "Oral nonprescription treatment zaleplon, zopiclone, and temazepam on for insomnia: an evaluation of products psychomotor performance". Aviat Space with limited evidence". Journal of clinical Environ Med 74 (12): 1263–70. PMID sleep medicine : JCSM : official 14692469. publication of the American Academy of [36] Zhdanova IV, Tucci V (May 2003). Sleep Medicine 1 (2): 173–87. PMID "Melatonin, Circadian Rhythms, and 17561634. Sleep" ( – Scholar search). Curr Treat [44] http://www.cannabis.net/medicalOptions Neurol 5 (3): 225–229. marijuana/pot-docs.html doi:10.1007/s11940-003-0013-0. PMID [45] Hornyak M, Voderholzer U, Hohagen F, 12670411. http://www.treatmentBerger M, Riemann D (1998). options.com/1092-8480/5/225. "Magnesium therapy for periodic leg [37] Rajaratnam, SMW; Polymeropoulos MH, movements-related insomnia and restless Fisher DM, Roth T, Scott C, Birznieks G, legs syndrome: an open pilot study". Klerman EB (2 December 2008). Sleep 21 (5): 501–5. PMID 9703590. "Melatonin agonist tasimelteon [46] "Cider Vinegar and Insomnia". (VEC-162) for transient insomnia after http://www.cidervinegar.org/2007/06/ sleep-time shift: two randomised cider-vinegar-rocks.html. controlled multicentre trials". Lancet 373: 482. doi:10.1016/ S0140-6736(08)61812-7. [38] Zammit G, Erman M, Wang-Weigand S, Sainati S, Zhang J, Roth T (August 2007). "Evaluation of the efficacy and safety of Retrieved from "http://en.wikipedia.org/wiki/Insomnia" Categories: Sleep disorders, Symptoms of bipolar disorder

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