Sustained Efficacy of Eszopiclone Over 6 Months of Nightly Treatment: Results of a Randomized, Double-Blind, Placebo-Controlled Study in Adults with Chronic Insomnia
Abstract
Study objectives To determine the long-term efficacy of eszopiclone in patients with chronic insomnia. Design Randomized, double-blind, multicenter, placebo-controlled. Setting Out-patient, with monthly visits. Patients Aged 21 to 69 years meeting DSM IV criteria for primary insomnia and reporting less than 6.5 hours of sleep per night, and/or a sleep latency of more than 30 minutes each night for at least 1 month before screening. Interventions Eszopiclone 3 mg (n = 593) or placebo (n = 195), nightly for 6 months Measurements and results Efficacy was evaluated weekly using an interactive voice-response system. Endpoints included sleep latency; total sleep time; number of awakenings; wake time after sleep onset; quality of sleep; and next-day ratings of ability to function, daytime alertness, and sense of physical well-being. At the first week and each month for the study duration, eszopiclone produced significant and sustained improvements in sleep latency, wake time after sleep onset, number of awakenings, number of nights awakened per week, total sleep time, and quality of sleep compared with placebo (P Conclusions Throughout 6 months, eszopiclone improved all of the components of insomnia as defined by DSM-IV, including patient ratings of daytime function. This placebo-controlled study of eszopiclone provides compelling evidence that long-term pharmacologic treatment of insomnia is efficacious.
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In clinical practice, hypnotic medications are often used over durations of one to twelve months without dosage escalation.
“In clinical practice, hypnotic medications are often used over durations of one to twelve months without dosage escalation, 52-55”
From Clinical Guideline for the Evaluation and Management of Chronic Insomnia in Adults (2008) · cites this paper as [52]
Cites
Behavioral and Pharmacological Therapies for Late-Life Insomnia: A Randomized Controlled Trial
Morin, C. M., Colecchi, C., Stone, J., Sood, R., & Brink, D. (1999) · JAMA · doi:10.1001/jama.281.11.991 · Cited by 1,095 · see citing works
Vgontzas, A. N., Bixler, E. O., Lin, H.-M., Prolo, P., Mastorakos, G., Vela-Bueno, A., Kales, A., & Chrousos, G. P. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.8.7778 · Cited by 884 · see citing works
Epidemiological Study on Insomnia in the General Population
Ohayon, M. (1996) · Sleep · doi:10.1093/sleep/19.suppl_3.s7 · Cited by 401 · see citing works
Buysse, D. J., Reynolds, C. F., Kupfer, D. J., Thorpy, M. J., Bixler, E., Manfredi, R., Kales, A., Vgontzas, A., Stepanski, E., Roth, T., et al. (1994) · Sleep · doi:10.1093/sleep/17.7.630 · Cited by 274 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
European guideline for the diagnosis and treatment of insomnia
Riemann, D., Baglioni, C., Bassetti, C., Bjorvatn, B., Dolenc Groselj, L., Ellis, J. G., Espie, C. A., Garcia‐Borreguero, D., Gjerstad, M., Gonçalves, M., et al. (2017) · Journal of Sleep Research · doi:10.1111/jsr.12594 · Cited by 2,049 · see citing works
Qaseem, A., Kansagara, D., Forciea, M. A., Cooke, M., Denberg, T. D., & for the Clinical Guidelines Committee of the American College of Physicians* (2016) · Annals of Internal Medicine · doi:10.7326/m15-2175 · Cited by 1,965 · see citing works
Clinical Guideline for the Evaluation and Management of Chronic Insomnia in Adults
Schutte-Rodin, S., Broch, L., Buysse, D., Dorsey, C., & Sateia, M. (2008) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.27286 · Cited by 1,943 · see citing works
Sateia, M. J., Buysse, D. J., Krystal, A. D., Neubauer, D. N., & Heald, J. L. (2017) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.6470 · Cited by 1,519 · see citing works
Self-citationRecommendations for a standard research assessment of insomnia
Buysse, D. J., Ancoli-Israel, S., Edinger, J. D., Lichstein, K. L., & Morin, C. M. (2006) · Sleep · doi:10.1093/sleep/29.9.1155 · Cited by 1,206 · see citing works
Morin, C. M., & Benca, R. (2012) · The Lancet · doi:10.1016/s0140-6736(11)60750-2 · Cited by 976 · see citing works
Wilson, S., Nutt, D., Alford, C., Argyropoulos, S., Baldwin, D., Bateson, A., Britton, T., Crowe, C., Dijk, D.-J., Espie, C., et al. (2010) · Journal of Psychopharmacology · doi:10.1177/0269881110379307 · Cited by 634 · see citing works
Self-citationRiemann, D., & Perlis, M. L. (2009) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2008.06.001 · Cited by 477 · see citing works
Fava, M., McCall, W. V., Krystal, A., Wessel, T., Rubens, R., Caron, J., Amato, D., & Roth, T. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.01.016 · Cited by 480 · see citing works
Mundt, J. C., Snyder, P. J., Cannizzaro, M. S., Chappie, K., & Geralts, D. S. (2007) · Journal of Neurolinguistics · doi:10.1016/j.jneuroling.2006.04.001 · Cited by 380 · see citing works
Wilson, S., Anderson, K., Baldwin, D., Dijk, D.-J., Espie, A., Espie, C., Gringras, P., Krystal, A., Nutt, D., Selsick, H., et al. (2019) · Journal of Psychopharmacology · doi:10.1177/0269881119855343 · Cited by 312 · see citing works
Self-citationTalbot, L. S., Maguen, S., Metzler, T. J., Schmitz, M., McCaslin, S. E., Richards, A., Perlis, M. L., Posner, D. A., Weiss, B., Ruoff, L., et al. (2014) · Sleep · doi:10.5665/sleep.3408 · Cited by 294 · see citing works
Daytime symptoms in primary insomnia: A prospective analysis using ecological momentary assessment
Buysse, D. J., Thompson, W., Scott, J., Franzen, P. L., Germain, A., Hall, M., Moul, D. E., Nofzinger, E. A., & Kupfer, D. J. (2007) · Sleep Medicine · doi:10.1016/j.sleep.2006.10.006 · Cited by 289 · see citing works
The assessment and management of insomnia: an update
Krystal, A. D., Prather, A. A., & Ashbrook, L. H. (2019) · World Psychiatry · doi:10.1002/wps.20674 · Cited by 256 · see citing works
Self-citationWalsh, J. K., Krystal, A. D., Amato, D. A., Rubens, R., Caron, J., Wessel, T. C., Schaefer, K., Roach, J., Wallenstein, G., & Roth, T. (2007) · Sleep · doi:10.1093/sleep/30.8.959 · Cited by 239 · see citing works
Self-citationROTH, T., WALSH, J., KRYSTAL, A., WESSEL, T., & ROEHRS, T. (2005) · Sleep Medicine · doi:10.1016/j.sleep.2005.06.004 · Cited by 230 · see citing works
Self-citationRegulation of GABAA Receptor Subunit Expression by Pharmacological Agents
Uusi-Oukari, M., & Korpi, E. R. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002063 · Cited by 213 · see citing works
Dell’osso, B., & Lader, M. (2013) · European Psychiatry · doi:10.1016/j.eurpsy.2011.11.003 · Cited by 210 · see citing works
Nutt, D. J., & Stahl, S. M. (2010) · Journal of Psychopharmacology · doi:10.1177/0269881109106927 · Cited by 163 · see citing works
Randomized trial of a cognitive-behavioral intervention for insomnia in breast cancer survivors
Epstein, D. R., & Dirksen, S. R. (2007) · Oncology nursing forum · doi:10.1188/07.onf.e51-e59 · Cited by 152 · see citing works
Sleep and Antidepressant Treatment
Wichniak, A., Wierzbicka, A., & Jernajczyk, W. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212803523608 · Cited by 142 · see citing works
Soares, C. N., Joffe, H., Rubens, R., Caron, J., Roth, T., & Cohen, L. (2006) · Obstetrics & Gynecology · doi:10.1097/01.aog.0000245449.97365.97 · Cited by 135 · see citing works
Self-citationThe association between insomnia and cardiovascular diseases
Spiegelhalder, K. (2010) · Nature and Science of Sleep · doi:10.2147/nss.s7471 · Cited by 107 · see citing works
Joffe, H., Petrillo, L., Viguera, A., Koukopoulos, A., Silver-Heilman, K., Farrell, A., Yu, G., Silver, M., & Cohen, L. S. (2010) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2009.10.868 · Cited by 106 · see citing works
Comparative Tolerability of Newer Agents for Insomnia
Zammit, G. (2009) · Drug Safety · doi:10.2165/11312920-000000000-00000 · Cited by 98 · see citing works
Patient characteristics and predictors of sleep medication use
Omvik, S., Pallesen, S., Bjorvatn, B., Sivertsen, B., Havik, O. E., & Nordhus, I. H. (2010) · International Clinical Psychopharmacology · doi:10.1097/yic.0b013e328334e5e6 · Cited by 95 · see citing works
Insomnia in women: an overlooked epidemic?
Soares, C. N. (2005) · Archives of Women's Mental Health · doi:10.1007/s00737-005-0100-1 · Cited by 89 · see citing works
Eszopiclone: A Review of Its Use in the Treatment of Insomnia
Hair, P. I., McCormack, P. L., & Curran, M. P. (2008) · Drugs · doi:10.2165/00003495-200868100-00005 · Cited by 59 · see citing works
Omvik, S., Sivertsen, B., Pallesen, S., Bjorvatn, B., Havik, O. E., & Nordhus, I. H. (2008) · Behaviour Research and Therapy · doi:10.1016/j.brat.2008.02.013 · Cited by 45 · see citing works
Pharmacokinetic evaluation of eszopiclone: clinical and therapeutic implications
Greenblatt, D. J., & Zammit, G. K. (2012) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2012.741588 · Cited by 28 · see citing works
2023 Guidelines on the Diagnosis and Treatment of Insomnia in Adults - Brazilian Sleep Association
Drager, L. F., Assis, M., Bacelar, A. F. R., Poyares, D. L. R., Conway, S. G., Pires, G. N., de Azevedo, A. P., Carissimi, A., Eckeli, A. L., Pentagna, Á., et al. (2023) · Sleep Science · doi:10.1055/s-0043-1776281 · Cited by 25 · see citing works
Restricting benzodiazepines to short-term prescription.
Krystal, J. H., Stossel, S., & Krystal, A. D. (2015) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2015.0351 · Cited by 12 · see citing works
Self-citationStelzer, F. G., Bacelar, A., Éckeli, A. L., Negrão, A. B., Almeida, C. M. O., Franco, C. M. R., Pires, G. N., Gitaí, L. L. G., Sobreira-Neto, M. A., Assis, M., et al. (2025) · Arquivos de Neuro-Psiquiatria · doi:10.1055/s-0045-1812323 · Cited by 1 · see citing works
Pharmacological principles for safe benzodiazepine and Z-drug dose reduction
Horowitz, M., Lamberson, N., Brandt, J., Framer, A., Shapiro, B., Sørensen, A., Cadogan, C., Ritvo, A., & Taylor, D. (2026) · Psychological Medicine · doi:10.1017/s0033291726104887
“While the benefits of benzodiazepines in acute syndromes are unchallenged for psychiatric indications (Krystal et al., 2003; Roth et al., 2005), the dangers of long-term prescribing are widely accepted (Olfson, King, & Schoenbaum, 2015).”
- Authors
- Krystal, A. D., Walsh, J. K., Laska, E., Caron, J., Amato, D. A., Wessel, T. C., & Roth, T.
- Affiliations
- Duke University (US)
- Saint Louis University (US)
- Nathan Kline Institute for Psychiatric Research (US)
- Sunovion (United States) (US)
- Henry Ford Hospital (US)
- Corresponding author
- Krystal, Andrew D.
- Venue
- Sleep
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-10
- Volume
- 26
- Issue
- 7
- Pages
- 793-799
- ISSN
- 0161-8105 (ISSN-L)
- 1550-9109
- OpenAlex
- W2099661804
- Cited by
- 630
- References
- 4
- Citations by year
- 2026: 12 · 2025: 3 · 2024: 7 · 2023: 16 · 2022: 6 · 2021: 13 · 2020: 165 · 2019: 14 · 2018: 16 · 2017: 13 · 2016: 14 · 2015: 13 · 2014: 24 · 2013: 13 · 2012: 29
- FWCI
- 38.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- SLEEP (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Health Sciences › Medicine › Physiology › Obstructive Sleep Apnea Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- eszopiclone, chronic insomnia, long-term efficacy, hypnotics, sleep latency, wake after sleep onset, sleep quality, daytime functioning, adverse events
- MeSH terms
- Adult, Aged, Chronic Disease, Circadian Rhythm, Double-Blind Method, Female, Humans, Hypnotics and Sedatives, Sleep Initiation and Maintenance Disorders, Male, Middle Aged, Piperazines, Time Factors, Wakefulness, Azabicyclo Compounds
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