Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2018 May 14;5(5):CD010753.
doi: 10.1002/14651858.CD010753.pub2.

Antidepressants for insomnia in adults

Hazel Everitt  1 , David S Baldwin, Beth Stuart, Gosia Lipinska, Andrew Mayers, Andrea L Malizia, Christopher Cf Manson, Sue Wilson
Affiliations
Meta-Analysis

Antidepressants for insomnia in adults

Hazel Everitt et al. Cochrane Database Syst Rev. .

Abstract

Background: Insomnia disorder is a subjective condition of unsatisfactory sleep (e.g. sleep onset, maintenance, early waking, impairment of daytime functioning). Insomnia disorder impairs quality of life and is associated with an increased risk of physical and mental health problems including anxiety, depression, drug and alcohol abuse, and increased health service use. hypnotic medications (e.g. benzodiazepines and 'Z' drugs) are licensed for sleep promotion, but can induce tolerance and dependence, although many people remain on long-term treatment. Antidepressant use for insomnia is widespread, but none is licensed for insomnia and the evidence for their efficacy is unclear. This use of unlicensed medications may be driven by concern over longer-term use of hypnotics and the limited availability of psychological treatments.

Objectives: To assess the effectiveness, safety and tolerability of antidepressants for insomnia in adults.

Search methods: This review incorporated the results of searches to July 2015 conducted on electronic bibliographic databases: the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 6), MEDLINE (1950 to 2015), Embase (1980 to 2015) and PsycINFO (1806 to 2015). We updated the searches to December 2017, but these results have not yet been incorporated into the review.

Selection criteria: Randomised controlled trials (RCTs) of adults (aged 18 years or older) with a primary diagnosis of insomnia and all participant types including people with comorbidities. Any antidepressant as monotherapy at any dose whether compared with placebo, other medications for insomnia (e.g. benzodiazepines and 'Z' drugs), a different antidepressant, waiting list control or treatment as usual.

Data collection and analysis: Two review authors independently assessed trials for eligibility and extracted data using a data extraction form. A third review author resolved disagreements on inclusion or data extraction.

Main results: The search identified 23 RCTs (2806 participants).Selective serotonin reuptake inhibitors (SSRIs) compared with placebo: three studies (135 participants) compared SSRIs with placebo. Combining results was not possible. Two paroxetine studies showed significant improvements in subjective sleep measures at six (60 participants, P = 0.03) and 12 weeks (27 participants, P < 0.001). There was no difference in the fluoxetine study (low quality evidence).There were either no adverse events or they were not reported (very low quality evidence).Tricyclic antidepressants (TCA) compared with placebo: six studies (812 participants) compared TCA with placebo; five used doxepin and one used trimipramine. We found no studies of amitriptyline. Four studies (518 participants) could be pooled, showing a moderate improvement in subjective sleep quality over placebo (standardised mean difference (SMD) -0.39, 95% confidence interval (CI) -0.56 to -0.21) (moderate quality evidence). Moderate quality evidence suggested that TCAs possibly improved sleep efficiency (mean difference (MD) 6.29 percentage points, 95% CI 3.17 to 9.41; 4 studies; 510 participants) and increased sleep time (MD 22.88 minutes, 95% CI 13.17 to 32.59; 4 studies; 510 participants). There may have been little or no impact on sleep latency (MD -4.27 minutes, 95% CI -9.01 to 0.48; 4 studies; 510 participants).There may have been little or no difference in adverse events between TCAs and placebo (risk ratio (RR) 1.02, 95% CI 0.86 to 1.21; 6 studies; 812 participants) (low quality evidence).'Other' antidepressants with placebo: eight studies compared other antidepressants with placebo (one used mianserin and seven used trazodone). Three studies (370 participants) of trazodone could be pooled, indicating a moderate improvement in subjective sleep outcomes over placebo (SMD -0.34, 95% CI -0.66 to -0.02). Two studies of trazodone measured polysomnography and found little or no difference in sleep efficiency (MD 1.38 percentage points, 95% CI -2.87 to 5.63; 169 participants) (low quality evidence).There was low quality evidence from two studies of more adverse effects with trazodone than placebo (i.e. morning grogginess, increased dry mouth and thirst).

Authors' conclusions: We identified relatively few, mostly small studies with short-term follow-up and design limitations. The effects of SSRIs compared with placebo are uncertain with too few studies to draw clear conclusions. There may be a small improvement in sleep quality with short-term use of low-dose doxepin and trazodone compared with placebo. The tolerability and safety of antidepressants for insomnia is uncertain due to limited reporting of adverse events. There was no evidence for amitriptyline (despite common use in clinical practice) or for long-term antidepressant use for insomnia. High-quality trials of antidepressants for insomnia are needed.

PubMed Disclaimer

Conflict of interest statement

HE: has no interests to declare.

DB: on behalf of his employer DB has held research grants from Bristol‐Myers Squibb, Cephalon, Eli Lilly Ltd, GlaxoSmithKline, H. Lundbeck A/S, Pierre Fabre, Pfizer Ltd, Roche and Vernalis Ltd. He has served on advisory boards hosted by Astra Zeneca, Bristol‐Myers Squibb, Eli Lilly Ltd, GlaxoSmithKline, Grünenthal, H. Lundbeck A/S, Pierre Fabre and Pfizer Ltd. He is a past president of Depression Alliance and current Medical Patron of Anxiety UK.

BS: has no interests to declare.

GL: has no interests to declare.

AMayers: has no interests to declare.

ALM: since medical qualification ALM has worked as Director of Clinical Pharmacology in SmithKlineBeecham and has dormant pension contributions through a third‐party pension provider. He has received research support from Wyeth, Medtronic and Organon on behalf of his employers at the time and been a speaker or accepted hospitality (or both) from Eli Lilly, Astra Zeneca, Lundbeck, Pfizer, Medtronic and Servier.

CCFM: has no interests to declare.

SW: has received honoraria for lectures from pharmaceutical companies making antidepressants, although none since 2009. SW has no financial interest in any pharmaceutical company.

Figures

1
1
Study flow diagram. SSRI: selective serotonin reuptake inhibitor; TCA: tricyclic antidepressant.
2
2
Summary of risk of bias across all included studies for each risk of bias item
3
3
4
4
Forest plot of comparison: 3 'Other' antidepressants versus placebo, outcome: 3.1 Subjective measure of sleep quality.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD010753

References

References to studies included in this review

Corruble 2013 {published data only}
    1. Corruble E, Bodinate C, Belaidi C, Goodwin GM. Efficacy of agomelatine and escitalopram on depression, subjective sleep and emotional experiences in patients with major depressive disorder: a 24 week randomised, controlled, double blind trial. International Journal of Neuropsychopharmacology 2013;16(10):2219‐34. - PubMed
Fava 2002 {published data only}
    1. Fava M, Hoog SL, Judge RA, Kopp JB, Nisson ME, Gonzales JS. Acute efficacy of fluoxetine versus sertraline and paroxetine in major depressive disorder including effects of baseline insomnia. Journal of Clinical Psychopharmacology 2002;22(2):137‐47. - PubMed
Finnerty 1978 {published data only}
    1. Finnerty RJ, Goldberg HL, Rickels K. Doxepin versus imipramine in psychoneurotic depressed patients with sleep disturbance: a double‐blind study. Journal of Clinical Psychiatry 1978;39(12):852‐6. - PubMed
Friedmann 2008 {published data only}
    1. Friedmann PD, Rose JS, Swift R. Trazodone for sleep disturbance after alcohol detoxification: a double‐blind, placebo‐controlled trial. Alcoholism Clinical Experimental Research 2008;32(9):1652‐60. - PMC - PubMed
Gillin 1997 {published data only}
    1. Gillin JC, Rapaport M, Erman MK, Winokur A, Albata BJ. A comparison of nefazodone and fluoxetine on mood and on objective, subjective, and clinician‐rated measures of sleep in depressed patients: a double‐blind, 8‐week clinical trial. Journal of Clinical Psychiatry 1997;58(5):185‐92. - PubMed
Hajak 2001 {published data only}
    1. Hajak G, Rodenbeck A, Voderholzer U, Riemann D, Cohrs S, Hohagen F, et al. Doxepin in the treatment of primary insomnia: a placebo‐controlled, double‐blind, polysomnographic study. Journal of Clinical Psychiatry 2001;62(6):453‐63. - PubMed
Khazaie 2013 {published data only}
    1. Khazaie H, Ghadami MR, Knight DC, Emamian F, Tahmasian M. Insomnia treatment in the third trimester of pregnancy reduces postpartum depression symptoms: a randomised clinical trial. Psychiatry Research 2013;210:901‐5. - PubMed
Krystal 2010 {published data only}
    1. Krystal AD, Durrence HH, Scharf M, Jochelson P, Rogowski R, Ludington E. Efficacy and safety of doxepin 1 mg and 3 mg in a 12‐week sleep laboratory and outpatient trial of elderly subjects with chronic primary insomnia. Sleep 2010;33(11):1553‐61. - PMC - PubMed
Krystal 2011 {published data only}
    1. Krystal AD, Lankford A, Durrence HH, Ludington E, Jochelson P, Rogowski R. Efficacy and safety of doxepin 3 and 6 mg in a 35‐day sleep laboratory trial in adults with chronic primary insomnia. Sleep 2011;34(10):1433‐42. - PMC - PubMed
Lankford 2012 {published data only}
    1. Lankford A, Rogowski R, Essink B, Ludington E, Durrence HH, Roth T. Efficacy and safety of doxepin 6 mg in a four‐week outpatient trial of elderly adults with chronic primary insomnia. Sleep Medicine 2012;13(2):133‐8. - PubMed
Le Bon 2003 {published data only}
    1. Bon O, Murphy JR, Staner L, Hoffmann G, Kormoss N, Kentos M. Double‐blind, placebo‐controlled study of the efficacy of trazodone in alcohol post‐withdrawal syndrome: polysomnographic and clinical evaluations. Journal of Clinical Psychopharmacology 2003;23(4):377‐83. - PubMed
Palomaki 2003 {published data only}
    1. Palomaki H, Berg A, Meririnne E, Kaste M, Lönnqvis R, Lehtihalmes M, et al. Complaints of post‐stroke insomnia and its treatment with mianserin. Cerebrovascular Diseases 2003;15(1‐2):56‐62. - PubMed
Reynolds 2006 {published data only}
    1. Reynolds CF, Buysse DJ, Miller MD, Pollock BG, Hall M, Mazumdar S. Paroxetine treatment of primary insomnia in older adults. American Journal of Geriatric Psychiatry 2006;14(9):803‐7. - PubMed
Riemann 2002 {published data only}
    1. Riemann D, Voderholzer U, Cohrs S, Rodenbeck A, Hajak G, Rüther E. Trimipramine in primary insomnia: results of a polysomnographic double‐blind controlled study. Pharmacopsychiatry 2002;35(5):165‐74. - PubMed
Rios Romenet 2013 {published data only}
    1. Rios Romenets S, Creti L, Fichten C, Bailes S, Libman E, Pelletier A. Doxepin and cognitive behavioural therapy for insomnia in patients with Parkinson's disease: a randomised study. Parkinsonism & Related Disorders 2013;19(7):670‐5. - PubMed
Roth 2011 {published data only}
    1. Roth AJ, McCall W, Liguori A. Cognitive, psychomotor and polysomnographic effects of trazodone in primary insomniacs. Journal of Sleep Research 2011;20(4):552‐58. - PMC - PubMed
Rush 1998 {published data only}
    1. Rush AJ, Armitage R, Gillin JC, Yonkers KA, Winkour A, Moldofsky H. Comparative effects of nefazodone and fluoxetine on sleep in outpatients with major depressive disorder. Biological Psychology 1998;44(1):3‐14. - PubMed
Satterlee 1995 {published data only}
    1. Satterlee WG, Faires D. The effects of fluoxetine on symptoms of insomnia in depressed patients. Psychopharmacological Bulletin 1995;31(2):227‐37. - PubMed
Shell 2012 {published data only}
    1. Shell WE, May LA, Bullias DH, Pavlik SL, Silver DS. Sentra PM (a medical food) and trazodone in the management of sleep disorders. Journal of Central Nervous System Diseases 2012;4:65‐72. - PMC - PubMed
Stein 2012 {published data only}
    1. Stein MD, Kurth, Sharkey KM, Anderson BJ, Corso RP, Millman RP. Trazodone for sleep disturbance during methadone maintenance: a double‐blind, placebo‐controlled trial. Drug and Alcohol Dependence 2012;120(1‐3):65‐73. - PMC - PubMed
Walsh 1998 {published data only}
    1. Walsh JK, Erman M, Erwin CW, Jamieson A, Mahowald M, Regestein Q. Subjective hypnotic efficacy of trazodone and zolpidem in DSMIII‐R primary insomnia. Human Psychopharmacology: Clinical and Experimental 1998;13(3):191‐8.
Ware 1989 {published data only}
    1. Ware JC, Brown FW, Moorad PJ, Pittard JT, Corbert B. Effects on sleep: a double‐blind study comparing trimipramine to imipramine in depressed insomniac patients. Sleep 1989;12(6):191‐8. - PubMed
Zhou 2002 {published data only}
    1. Zhou CL, Xie HJ, Wang LQ, Tang X. Clinical observation on effects of paroxetine and alprazolam in the treatment of elderly patients with chronic primary insomnia. Chinese Journal of Geriatrics 2002;21(3):185‐7.

References to studies excluded from this review

Adam 1979 {published data only}
    1. Adam K, Oswald I. One gram of L‐tryptophan fails to alter the time taken to fall asleep. Neuropharmacology 1979;18(12):1025‐7. - PubMed
Botros 1989 {published data only}
    1. Botros WA, Ankier SI, Priest RG, McManus IC, Samir ZY. Clinical assessment and performance tasks in depression: a comparison of amitriptyline and trazodone. British Journal of Psychiatry 1989;155:479‐82. - PubMed
Boyle 2012 {published data only}
    1. Boyle J, Eriksson ME, Grible L, Gouni R, Johnsen S, Coppini DV. Randomised, placebo‐controlled comparison of amitriptyline, duloxetine, and pregabaline in patients with chronic diabetic peripheral neuropathic pain: impact on pain, polysomnographic sleep, daytime functioning, and quality of life. Diabetes Care 2012;35(12):2451‐8. - PMC - PubMed
Carney 2017 {published data only}
    1. Carney CE, Edinger JD, Kuchibhatla M, Lachowski AM, Bogouslavsky O, Krystal AD. Cognitive behavioral insomnia therapy for those with insomnia and depression: a randomized controlled clinical trial [NCT00620789]. Sleep 2017;40:4. - PMC - PubMed
Chen 2002 {published data only}
    1. Chen X, Zheng HM, Shun XJ. Comparison of trazodone and paroxetine in treating dyssomnia of anxiety disorder. Chinese Journal of New Drugs and Clinical Remedies 2002;21(12):727‐30.
Fairweather 1997 {published data only}
    1. Fairweather DB, Stanley N, Hindmarch I. Fluoxetine and dothiepin in depressed patients: a comparison of efficacy and effects on cognition and subjective sleep. European Neuropsychopharmacology 1997;7(S2):148.
Ferrero 1987 {published data only}
    1. Ferrero F, Zahnd J. Tryptophan in the treatment of insomnia in hospitalised psychiatric patients. Encephale 1987;13(1):35‐7. - PubMed
Hajak 1996 {published data only}
    1. Hajak G, Rodenbeck A, Adler L, Huether G, Bandelow B, Herrendorf G. Nocturnal melatonin secretion and sleep after doxepin administration in chronic primary insomnia. Pharmacopsychiatry 1996;29(5):187‐92. - PubMed
Herman 2009 {published data only (unpublished sought but not used)}
    1. Herman B, Mychaskiw M, Mandel F. Comparison of sleep outcomes in generalized anxiety disorder following treatment with pregabalin or venlafaxine‐XR. European Psychiatry 2009;24 (Suppl 1):S528.
    1. Mychaskiw MA, Alvir JM, Herman BK, Pallanti S, Joshi A. Insomnia and quality of life in generalized anxiety disorder: impact on clinical presentation and response to pregabalin and venlafaxine‐XR. European Psychiatry 2009;24 (Suppl 1):S534.
Karsten 2017 {published data only}
    1. Karsten J, Hagenauw La, Kamphuis J, Lancel M. Low doses of mirtazapine or quetiapine for transient insomnia: a randomised, double‐blind, cross‐over, placebo‐controlled trial. Journal of Psychopharmacology 2017;31(3):327‐37. - PubMed
Kaynak 2004 {published data only}
    1. Kaynak H, Kaynak D, Gözükirmizi E, Guilleminault C. The effects of trazodone on sleep in patients treated with stimulant antidepressants. Sleep Medicine 2004;5(1):15‐20. - PubMed
Moon 1991 {published data only}
    1. Moon CAL, Pownall R. A double‐blind study of the effects of Dothiepin (75/150 mg nocte) on sleep and morning psychomotor function. British Journal of Clinical Research 1991;2:21‐31.
Palesh 2012 {published data only}
    1. Palesh O, Mustian KM, Roscoe JA, Morrow GR, Perlis ML, Heckler CE. Impact of paroxetine on sleep problems in 426 cancer patients receiving chemotherapy: a trial from the University of Rochester Cancer Center Community Clinical Oncology Program. Sleep Medicine 2012;13(9):1184‐90. - PMC - PubMed
Roth 2007 {published data only}
    1. Roth T, Rogowski R, Hull S, Schwartz H, Koshorek G, Corser B. Efficacy and safety of doxepin 1 mg, 3 mg, and 6 mg in adults with primary insomnia. Sleep 2007;30(11):1555‐61. - PMC - PubMed
Ruwe 2016 {published data only}
    1. Ruwe F, Ijzerman‐Boon P, Roth T, Zammit G, Ivgy‐May N. A phase 2 randomized dose‐finding study with esmirtazapine in patients with primary insomnia. Journal of Clinical Psychopharmacology 2016;36(5):457‐64. - PubMed
Scharf 2008 {published data only}
    1. Scharf M, Rogowski R, Hull S, Cohn M, Mayleben D, Feldman N. Efficacy and safety of doxepin 1 mg, 3 mg, and 6 mg in elderly patients with primary insomnia: a randomized, double‐blind, placebo‐controlled crossover study. Journal of Clinical Psychiatry 2008;69(10):1557‐64. - PubMed
Stein 2011 {published data only}
    1. Stein DJ, Lopez AG. Effects of escitalopram on sleep problems in patients with major depression or generalized anxiety disorder. Advances in Therapy 2011;28(11):1021‐37. - PubMed
Stephenson 2000 {published data only}
    1. Stephenson DA, Harris B, Davies RH, Mullin JM. The impact of antidepressants on sleep and anxiety: a comparative study of fluoxetine and dothiepin using the Leeds Sleep Evaluation Questionnaire. Human Psychopharmacology 2000;15(7):529‐34. - PubMed

References to studies awaiting assessment

Ahmed 2016 {published data only}
    1. Ahmed M, Aamir R, Jishi Z, Scharf MB. The effects of milnacipran on sleep disturbance in fibromyalgia: a randomized, double‐blind, placebo‐controlled, two‐way crossover study. Journal of Clinical Sleep Medicine 2016;12(1):79‐86. - PMC - PubMed
Ivgy‐May 2015a {published data only}
    1. Ivgy‐May N, Ruwe F, Krystal A, Roth T. Esmirtazapine in non‐elderly adult patients with primary insomnia: efficacy and safety from a randomized, 6‐week sleep laboratory trial. Sleep Medicine 2015;16:838‐44. - PubMed
Ivgy‐May 2015b {published data only}
    1. Ivgy‐May N, Roth T, Ruwe F, Walsh J. Esmirtazapine in non‐elderly adult patients with primary insomnia: efficacy and safety from a 2‐week randomized outpatient trial. Sleep Medicine 2015;16(7):831‐7. - PubMed
Krystal 2012 {published data only}
    1. Krystal AD, Roth T, Pong A, Stet L, Ivgy‐May N. Efficacy and safety of esmirtazapine in elderly patients with primary insomnia in a 2‐week sleep laboratory trial. Sleep 2012;35:A222. - PubMed
Merck 2008 {published data only}
    1. Merck Sharp, Dohme Corp. A 6‐month efficacy and safety study of org 50081 in adult patients with chronic primary insomnia (21106/P05701/MK‐8265‐002). ClinicalTrials.gov/show/NCT00631657 Date first registered: 10 March 2008.
Miljatovic 2012 {published data only}
    1. Miljatovic AM. Comparative effects of venlafaxine and mirtazepine on sleep physiology measures in patients with major depressive disorder and insomnia. European Psychiatry 2012;27 (Suppl 1):1.
Shirazi 2016 {published data only}
    1. Shirazi M, Saedi N, Shariat M, Azadi F, Tanha FD. Comparison of melissa with citalopram and placebo in treatment of sleep disorders in menopausal women: clinical trial. Tehran University Medical Journal 2016;74(8):562‐8.
Wu 2015 {published data only}
    1. Wu J, Chang F, Zu H. Efficacy and safety evaluation of citalopram and doxepin on sleep quality in comorbid insomnia and anxiety disorders. Experimental and Therapeutic Medicine 2015;10:1303‐8. - PMC - PubMed

References to ongoing studies

ChiCTR‐IPR‐16009475 {published data only}
    1. ChiCTR‐IPR‐16009475, Shanghai Mental Health Center. The research of chronic insomnia clinical evaluation and optimization of treatment. www.chictr.org.cn/showproj.aspx?proj=16136 Date first registered: 18 October 2016.
Morin 2015 {published data only (unpublished sought but not used)}
    1. Morin CM, Edinger JD, Krystal AD, Beaulieu‐Bonneau S, Ivers H, Guay B, et al. Sequenced therapies for comorbid and primary insomnia: preliminary findings of a randomized controlled trial. Sleep 2015;40 (Suppl 1):A127.
NCT02139098 {published data only}
    1. NCT02139098. Alternative dosing regimens in the pharmacotherapy of insomnia (ALPHASOM). clinicaltrials.gov/ct2/show/NCT02139098 Date first registered: 15 May 2014.

Additional references

Altena 2008
    1. Altena E, Werf YD, Strijers RL, Someren EJ. Sleep loss affects vigilance: effects of chronic insomnia and sleep therapy. Journal of Sleep Research 2008;17(3):335‐43. - PubMed
Auld 2017
    1. Auld F, Maschauer EL, Morrison I, Skene DJ, Riha RL. Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders. Sleep Med Rev. 2017;34:10‐22. - PubMed
Aversa Lopes 2009
    1. Aversa Lopes E, Silva AB, Macedo CR, Soares B, Saconato H, Atallah ÁN. Cognitive behavioural therapy for insomnia. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD006814] - DOI
Baglioni 2011
    1. Baglioni C, Battagliese G, Feige B, Spiegelhalder K, Nissen C, Voderholzer U. Insomnia as a predictor of depression: a meta‐analytic evaluation of longitudinal epidemiological studies. Journal of Affective Disorders 2011;135:1‐19. - PubMed
Balter 1992
    1. Balter MB, Uhlenhuth EH. New epidemiologic findings about insomnia and its treatment. Journal of Clinical Psychiatry 1992;53 Suppl:34‐9. - PubMed
Breslau 1996
    1. Breslau N, Roth T, Rosenthal L, Andreski P. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biological Psychiatry 1996;39(6):411‐8. - PubMed
Buscemi 2007
    1. Buscemi N, Vandermeer B, Friesen C, Bialy L, Tubman M, Ospina M. The efficacy and safety of drug treatments for chronic insomnia in adults: a meta‐analysis of RCTs. Journal of General Internal Medicine 2007;22(9):1335‐50. - PMC - PubMed
Buysse 1989
    1. Buysse DJ, Reynolds III CF, Monk TH, Berman SB, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Research 1989;28:193‐213. - PubMed
Cheuk 2012
    1. Cheuk DK, Yeung WF, Chung KF, Wong V. Acupuncture for insomnia. Cochrane Database of Systematic Reviews 2012, Issue 9. [DOI: 10.1002/14651858.CD005472.pub3] - DOI
Chevalier 1999
    1. Chevalier H, Los F, Boichut D, Bianchi M, Nutt DJ, Hajak G. Evaluation of severe insomnia in the general population: results of a European multinational survey. Journal of Psychopharmacology 1999;13(4 Suppl 1):21‐4. - PubMed
Committee on Safety of Medicines 1988
    1. Committee on Safety of Medicines. Benzodiazepines, dependence and withdrawal symptoms. Medicines Control Agency 1988;21:1‐2.
DSM‐V 2015
    1. American Psychiatric Association. Insomnia disorder. Diagnostic and Statistical Manual of Mental Disorders, 5th edition 2015.
Edinger 2008
    1. Edinger JD, Means MK, Carney CE, Krystal AD. Psychomotor performance deficits and their relation to prior nights' sleep among individuals with primary insomnia. Sleep 2008;31(5):599‐607. - PMC - PubMed
Everitt 2014
    1. Everitt H, McDermott L, Leydon G, Yules H, Baldwin D, Little P. General practitioners' management strategies for patients with insomnia: a survey and qualitative interview study. British Journal of General Practice 2014;64:88‐9. - PMC - PubMed
Hamilton 1960
    1. Hamilton M. A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry 1960;23:56‐62. - PMC - PubMed
Higgins 2011
    1. Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Ishigooka 1999
    1. Ishigooka J, Suzuki M, Isawa S, Muraoka H, Murasaki M, Okawa M. Epidemiological study on sleep habits and insomnia of new outpatients visiting general hospitals in Japan. Psychiatry and Clinical Neurosciences 1999;53(4):515‐22. - PubMed
Krystal 2003
    1. Krystal AD, Walsh JK, Laska E, Caron J, Amato DA, Wessel TC, et al. Sustained efficacy of eszopiclone over 6 months of nightly treatment: results of a randomized, double‐blind, placebo‐controlled study in adults with chronic insomnia. Sleep 2003;26(7):793‐9. - PubMed
Krystal 2008
    1. Krystal AD, Erman M, Zammit GK, Soubrane C, Roth T. Long‐term efficacy and safety of zolpidem extended‐release 12.5 mg, administered 3 to 7 nights per week for 24 weeks, in patients with chronic primary insomnia: a 6‐month, randomized, double‐blind, placebo‐controlled, parallel‐group, multicenter study. Sleep 2008;31(1):79‐90. - PMC - PubMed
Krystal 2009
    1. Krystal AD. A compendium of placebo‐controlled trials of the risks/benefits of pharmacological treatments for insomnia: the empirical basis for U.S. clinical practice. Sleep Medicine Reviews 2009;13(4):265‐74. - PubMed
Lai 2011
    1. Lai L, Tan MH, Lai YC. Prevalence and factors associated with off‐label antidepressant prescriptions for insomnia. Drug, Healthcare and Patient Safety 2011;3:27‐36. - PMC - PubMed
LeBlanc 2009
    1. LeBlanc M, Merette C, Savard J, Ivers H, Baillargeon L, Morin CM. Incidence and risk factors of insomnia in a population‐based sample. Sleep 2009;32(8):1027‐37. - PMC - PubMed
Leger 2001
    1. Leger D, Scheuermaier K, Philip P, Paillard M, Guilleminault C. SF‐36: evaluation of quality of life in severe and mild insomniacs compared with good sleepers. Psychosomatic Medicine 2001;63(1):49‐55. - PubMed
Lemoine 2007
    1. Lemoine P, Nir T, Laudon M, Zisapel N. Prolonged‐release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. Journal of Sleep Research 2007;16(4):372‐80. - PubMed
Mayer 2009
    1. Mayer G, Wang‐Weigand S, Roth‐Schechter B, Lehmann R, Staner C, Partinen M. Efficacy and safety of 6‐month nightly ramelteon administration in adults with chronic primary insomnia. Sleep 2009;32(3):351‐60. - PMC - PubMed
Mayers 2005
    1. Mayers AG, Baldwin DS. Antidepressants and their effect on sleep. Human Psychopharmacology 2005;20(8):533‐59. - PubMed
Mellinger 1985
    1. Mellinger GD, Balter MB, Uhlenhuth EH. Insomnia and its treatment. Prevalence and correlates. Archives of General Psychiatry 1985;42(3):225‐32. - PubMed
Moher 2009
    1. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta‐analyses: the PRISMA statement. PLoS Medicine 2009;6(7):e1000097. - PMC - PubMed
Morin 1999
    1. Morin CM, Colecchi C, Stone J, Sood R, Brink D. Behavioral and pharmacological therapies for late‐life insomnia: a randomized controlled trial. Journal of the American Medical Association 1999;281(11):991‐9. - PubMed
Morin 2003
    1. Morin CM, Rodrigue S, Ivers H. Role of stress, arousal, and coping skills in primary insomnia. Psychosomatic Medicine 2003;65(2):259‐67. - PubMed
Morin 2011
    1. Morin CM, Belleville G, Belanger L, Ivers H. The Insomnia Severity Index: psychometric indicators to detect insomnia cases and evaluate treatment response. Sleep 2011;34(5):603‐8. - PMC - PubMed
Morlock 2006
    1. Morlock RJ, Tan M, Mitchell DY. Patient characteristics and patterns of drug use for sleep complaints in the United States: analysis of national ambulatory medical survey data, 1997‐2002. Clinical Therapeutics 2006;28(7):1044‐53. - PubMed
Neckelmann 2007
    1. Neckelmann D, Mykletun A, Dahl AA. Chronic insomnia as a risk factor for developing anxiety and depression. Sleep 2007;30(7):873‐80. - PMC - PubMed
NHS Digital 2011
    1. NHS Digital. Prescription Cost Analysis England 2010. digital.nhs.uk/data‐and‐information/publications/statistical/prescriptio... 2011 (accessed June 2011).
NICE 2004
    1. National Institute for Clinical Excellence (NICE). Guidance on the use of zaleplon, zolpidem and zopiclone for the short‐term management of insomnia (Technology Appraisal 77). www.nice.org.uk/guidance/ta77 (accessed 12 September 2013). London: NICE, 2004.
NIH 1983
    1. National institute of Health Consensus Development Programme. Drugs and insomnia: the use of medications to promote sleep. consensus.nih.gov/1983/1983insomniadrugs039html.htm 1983.
NIH 2005
    1. NIH. National Institutes of Health State of the Science conference statement on manifestations and management of chronic insomnia in adults. Sleep 2005;28(9):1049‐57. - PubMed
Nissen 2011
    1. Nissen C, Kloepfer C, Feige B, Piosczyk H, Spiegelhalder K, Voderholzer U. Sleep‐related memory consolidation in primary insomnia. Journal of Sleep Research 2011;20(1 Pt 2):129‐36. - PubMed
Ohayon 1999
    1. Ohayon MM, Caulet M, Arbus L, Billard M, Coquerel A, Guieu JD. Are prescribed medications effective in the treatment of insomnia complaints?. Journal of Psychosomatic Research 1999;47(4):359‐68. - PubMed
Perlis 2010
    1. Perlis M, Shaw P, Cano G, Espie C. Chapter 78: models of insomnia. In: Kryger M, Roth T, Dement W editor(s). Principles and Practice of Sleep Medicine. 5th Edition. St Louis (MO): Saunders, 2010:850‐65.
Philip 2006
    1. Philip P, Leger D, Taillard J, Quera‐Salva MA, Niedhammer I, Mosqueda JG. Insomniac complaints interfere with quality of life but not with absenteeism: respective role of depressive and organic comorbidity. Sleep Medicine 2006;7(7):585‐91. - PubMed
Review Manager 2014 [Computer program]
    1. Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Riemann 2009
    1. Riemann D, Perlis, ML. The treatments of chronic insomnia: a review of benzodiazepine receptor agonists and psychological and behavioural therapies. Sleep Medicine Reviews 2009;13:205‐14. - PubMed
Saarto 2010
    1. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain: a Cochrane review. Journal of Neurology, Neurosurgery and Psychiatry 2010;81(12):1372‐3. - PubMed
Sateia 2004
    1. Sateia MJ, Nowell PD. Insomnia. Lancet 2004;364(9449):1959‐73. - PubMed
Sivertsen 2009
    1. Sivertsen B, Krokstad S, Mykletun A, Overland S. Insomnia symptoms and use of health care services and medications: the HUNT‐2 study. Behavioral Sleep Medicine 2009;7(4):210‐22. - PubMed
Thaler 2012
    1. Thaler KJ, Morgan LC, Noord M, Gaynes BN, Hansen R, Lux L, et al. Comparative effectiveness of second‐generation antidepressants for accompanying anxiety insomnia and pain in depressed patients: a systematic review. Depression and Anxiety 2012;29(6):495‐505. - PubMed
Vgontzas 2009
    1. Vgontzas AN, Liao D, Bixler EO, Chrousos GP, Vela‐Bueno A. Insomnia with objective short sleep duration is associated with a high risk for hypertension. Sleep 2009;32(4):491‐7. - PMC - PubMed
Wade 2007
    1. Wade AG, Ford I, Crawford G, McMahon AD, Nir T, Laudon M. Efficacy of prolonged release melatonin in insomnia patients aged 55‐80 years: quality of sleep and next‐day alertness outcomes. Current Medical Research and Opinion 2007;23(10):2597‐605. - PubMed
Walsh 2007
    1. Walsh JK, Krystal AD, Amato DA, Rubens R, Caron J, Wessel TC. Nightly treatment of primary insomnia with eszopiclone for six months: effect on sleep, quality of life, and work limitations. Sleep 2007;30(8):959‐68. - PMC - PubMed
WHO 1992
    1. World Health Organization. ICD‐10 Classifications of Mental and Behavioural Disorder: Clinical Descriptions and Diagnostic Guidelines. Geneva: World Health Organization, 1992.
Wilson 2005
    1. Wilson S, Argyropoulos S. Antidepressants and sleep: a qualitative review of the literature. Drugs 2005;65(7):927‐47. - PubMed
Wilson 2010
    1. Wilson SJ, Nutt DJ, Alford C, Argyropoulos SV, Baldwin DS, Bateson AN. British Association for Psychopharmacology consensus statement on evidence‐based treatment of insomnia, parasomnias and circadian rhythm disorders. Journal of Psychopharmacology 2010;24(11):1577‐601. - PubMed

MeSH terms