21 Z-Drugs
Table of Contents
21.1 Pharmaceutical Industry. 1
21.11 Adverse Effects: General 12
21.12 Adverse Effects: By Organ System.. 12
21.13 Adverse Effects: Executive Function – Multiple Function Studies. 14
21.14 Adverse Effects: Executive Function – Single Function Studies. 15
21.15 Adverse Effects: Non-medical Use. 16
21.16 Z Drugs in Subpopulations. 18
21.1 Pharmaceutical Industry |
Eszoplicone
Prescribing Information: Lunesta
Zaleplon
Prescribing Information: Sonata
Zopiclone
Prescribing Information: Imovane
Zolpidem
Prescribing Information: Ambien
21.2 Reviews |
Expert Opinion
[No authors listed] Hypnotic dependence: zolpidem and zopiclone too. Prescrire Int. 2001;10(51):15. Abstract
Calamaro C. Sleeping through the night: are extended-release formulations the answer? J Am Acad Nurse Pract. 2008;20(2):69-75. Abstract
Hoffmann F. Benefits and risks of benzodiazepines and Z-drugs: comparison of perceptions of GPs and community pharmacists in Germany. Ger Med Sci. 2013;11:Doc10. Article
Nutt DJ. NICE: The National Institute of Clinical Excellence – or Eccentricity? Reflections on the Z-drugs as hypnotics. J Psychopharmacol. 2005;19(2):125-7. Link
Guidelines
National Institute for Clinical Excellence. Guidance on the Use of Zaleplon, Zolpidem and Zopiclone for the Short-term Management of Insomnia, Technology Appraisal 77. London, England: NICE; 2004. Document
Sateia MJ, Buysse DJ, Krystal AD, et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017;13(2):307-349. Abstract
Meta – Analyses
Reviews
Dündar Y, Boland A, Strobl J, et al. Newer hypnotic drugs for the short-term management of insomnia: a systematic review and economic evaluation. Health Technol Assess. 2004;8(24):iii-x, 1-125. Article
Schroeck JL, Ford J, Conway EL, et al. Review of safety and efficacy of sleep medicines in older adults. Clin Ther. 2016;38(11):2340-72. Abstract
Terzano MG, Rossi M, Palomba V, et al. New drugs for insomnia: comparative tolerability of zopiclone, zolpidem and zaleplon. Drug Saf. 2003;26(4):261-82. Abstract
21.3 Perspectives |
Pharmacists
Hoffmann F. Benefits and risks of benzodiazepines and Z-drugs: comparison of perceptions of GPs and community pharmacists in Germany. Ger Med Sci. 2013;11:Doc10. Article
Physicians, Physician Assistants, Nurse Practitioners
Hoffmann F, Schmiemann G, Windt R. Perceptions of GPs and community pharmacists on hypnotic prescribing on private prescriptions. Dtsch Med Wochenschr. 2014;139(22):1153-8. Abstract
Hoffmann F. Benefits and risks of benzodiazepines and Z-drugs: comparison of perceptions of GPs and community pharmacists in Germany. Ger Med Sci. 2013;11:Doc10. Article
21.4 Eszopiclone |
Brand: Lunesta Estorra
Prescribing Information: Lunesta
[No authors listed] Eszopiclone: esopiclone, estorra, S-zopiclone, zopiclone – Sepracor. Drugs R D. 2005;6(2):111-5. Abstract
Fava M, McCall WV, Krystal A, et al. Eszopiclone co-administered with fluoxetine in patients with insomnia coexisting with major depressive disorder. Biol Psychiatry. 2006;59(11):1052-60. Abstract
Hair PI, McCormack PL, Curran MP. Spotlight on eszopiclone in insomnia. CNS Drugs. 2008;22(11):975-8. Abstract
Hair PI, McCormack PL, Curran MP. Eszopiclone: a review of its use in the treatment of insomnia. Drugs. 2008;68(10):1415-34. Abstract
Krystal A, Fava M, Rubens R, et al. Evaluation of eszopiclone discontinuation after co-therapy with fluoxetine for insomnia with coexisting depression. J Clin Sleep Med. 2007;3(1):48-55. Abstract
Krystal AD, Walsh JK, Laska E, 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. Abstract
McCall WV, Erman M, Krystal AD, et al. A polysomnography study of eszopiclone in elderly patients with insomnia. Curr Med Res Opin. 2006;22(9):1633-42. Abstract
Najib J. Eszopiclone, a nonbenzodiazepine sedative-hypnotic agent for the treatment of transient and chronic insomnia. Clin Ther. 2006;28(4):491-516. Abstract
Pollack M, Kinrys G, Krystal A, et al. Eszopiclone coadministered with escitalopram in patients with insomnia and comorbid generalized anxiety disorder. Arch Gen Psychiatry. 2008;65(5):551-62. Abstract
Rosenberg R, Caron J, Roth T, Amato D. An assessment of the efficacy and safety of eszopiclone in the treatment of transient insomnia in healthy adults. Sleep Med. 2005;6(1):15-22. Abstract
Roth T, Walsh JK, Krystal A, et al. An evaluation of the efficacy and safety of eszopiclone over 12 months in patients with chronic primary insomnia. Sleep Med. 2005;6(6):487-95. Abstract
Scharf M. Eszopiclone for the treatment of insomnia. Expert Opin Pharmacother. 2006;7(3):345-56. Abstract
Walsh JK, Krystal AD, Amato DA, et al. 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. Article
Zammit GK, McNabb LJ, Caron J, et al. Efficacy and safety of eszopiclone across 6-weeks of treatment for primary insomnia. Curr Med Res Opin. 2004;20(12):1979-91. Abstract
21.5 Zaleplon |
Brand: Sonata
Prescribing Information: Sonata
Barbera J, Shapiro C. Benefit-risk assessment of zaleplon in the treatment of insomnia. Drug Saf. 2005;28(4):301-18. Abstract
Dooley M, Plosker GL. Zaleplon: a review of its use in the treatment of insomnia. Drugs. 2000;60(2):413-45. Abstract
Elie R, Rüther E, Farr I, et al. Sleep latency is shortened during 4 weeks of treatment with zaleplon, a novel nonbenzodiazepine hypnotic. Zaleplon Clinical Study Group. J Clin Psychiatry. 1999;60(8):536-44. Abstract
Fry J, Scharf M, Mangano R, Fujimori M. Zaleplon improves sleep without producing rebound effects in outpatients with insomnia. Zaleplon Clinical Study Group. Int Clin Psychopharmacol. 2000;15(3):141-52. Abstract
Huang YS, Hsu SC, Liu SI, Chen CK. A double-blind, randomized, comparative study to evaluate the efficacy and safety of zaleplon versus zolpidem in shortening sleep latency in primary insomnia. Chang Gung Med J. 2011;34(1):50-6. Abstract
Israel AG, Kramer JA. Safety of zaleplon in the treatment of insomnia. Ann Pharmacother. 2002;36(5):852-9. Abstract
21.6 Zopiclone |
Brand: Imovane
Prescribing Information: Imovane
Anderson AA. Zopiclone and nitrazepam: a multicenter placebo controlled comparative study of efficacy and tolerance in insomniac patients in general practice. Sleep. 1987;10 Suppl 1:54-62. Abstract
Dehlin O, Rundgren A, Börjesson L, et al. Zopiclone to geriatric patients. A parallel double-blind dose-response clinical trial of zopiclone as a hypnotic to geriatric patients – a study in a geriatric hospital. Pharmacology. 1983;27 Suppl 2:173-8. Abstract
Dehlin O, Rundgren A, Börjesson L, et al. Zopiclone to geriatric patients. A parallel double-blind dose-response clinical trial of zopiclone as a hypnotic to geriatric patients – a study in a geriatric hospital. Int Pharmacopsychiatry. 1982;17 Suppl 2:173-8. Abstract
Elie R, Lavoie G, Bourgouin J, Le Morvan P. Zopiclone versus flurazepam in insomnia: prolonged administration and withdrawal. Int Clin Psychopharmacol. 1990;5(4):279-86. Abstract
Elie R, Deschenes JP. Efficacy and tolerance of zopiclone in insomniac geriatric patients. Int Pharmacopsychiatry. 1982;17 Suppl 2:179-87. Abstract
Goa KL, Heel RC. Zopiclone. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy as an hypnotic. Drugs. 1986;32(1):48-65. Abstract
Musch B, Maillard F. Zopiclone, the third generation hypnotic: a clinical overview. Int Clin Psychopharmacol. 1990;5 Suppl 2:147-58. Abstract
Ngen CC, Hassan R. A double-blind placebo-controlled trial of zopiclone 7.5 mg and temazepam 20 mg in insomnia. Int Clin Psychopharmacol. 1990;5(3):165-71. Abstract
Noble S, Langtry HD, Lamb HM. Zopiclone. An update of its pharmacology, clinical efficacy and tolerability in the treatment of insomnia. Drugs. 1998;55(2):277-302. Abstract
Ponciano E, Freitas F, Camara J, et al. A comparison of the efficacy, tolerance and residual effects of zopiclone, flurazepam and placebo in insomniac outpatients. Int Clin Psychopharmacol. 1990;5 Suppl 2:69-77. Abstract
Roehrs TA, Roth T. Gender differences in the efficacy and safety of chronic nightly zolpidem. J Clin Sleep Med. 2016;12(3):319-25. Article
Verster JC, Spence DW, Shahid A, et al. Zopiclone as positive control in studies examining the residual effects of hypnotic drugs on driving ability. Curr Drug Saf. 2011;6(4):209-18. Abstract
Wadworth AN, McTavish D. Zopiclone. A review of its pharmacological properties and therapeutic efficacy as an hypnotic. Drugs Aging. 1993;3(5):441-59. Abstract
Wheatley D. Insomnia in general practice: the role of temazepam and a comparison with zopiclone. Acta Psychiatr Scand Suppl. 1986;332:142-8. Abstract
Wheatley D. Zopiclone: a non-benzodiazepine hypnotic. Controlled comparison to temazepam in insomnia. Br J Psychiatry. 1985;146:312-4. Abstract
Wickstrøm E, Giercksky KE. Comparative study of zopiclone, a novel hypnotic, and three benzodiazepines. Eur J Clin Pharmacol. 1980;17(2):93-9. Abstract
21.7 Zolpidem |
Brand: Ambien
Prescribing Information: Ambien
Barkin RL. Zolpidem extended-release: a single insomnia treatment option for sleep induction and sleep maintenance symptoms. Am J Ther. 2007;14(3):299-305. Abstract
Benavides J, Depoortere H, Sanger D, et al. A specific domain (the omega 1 site) of the GABA(A) receptor may be implicated in the hypnotic effects of zolpidem. Encephale. 1990;16(1):13-22. Abstract
Bogan RK. Treatment options for insomnia – pharmacodynamics of zolpidem extended-release to benefit next-day performance. Postgrad Med. 2008;120(3):161-71. Abstract
Darcourt G, Pringuey D, Sallière D, Lavoisy J. The safety and tolerability of zolpidem – an update. J Psychopharmacol. 1999;13(1):81-93. Abstract
Depoortere H, Zivkovic B, Lloyd KG, et al. Zolpidem, a novel nonbenzodiazepine hypnotic. I. Neuropharmacological and behavioral effects. J Pharmacol Exp Ther. 1986;237(2):649-58. Abstract
Doghramji PP. Insomnia: zolpidem extended-release for the treatment of sleep induction and sleep maintenance symptoms. MedGenMed. 2007;9(1):11. Article
Greenblatt DJ, Roth T. Zolpidem for insomnia. Expert Opin Pharmacother. 2012;13(6):879-93. Abstract
Hoehns JD, Perry PJ. Zolpidem: a nonbenzodiazepine hypnotic for treatment of insomnia. Clin Pharm. 1993;12(11):814-28. Abstract
Holm KJ, Goa KL. Zolpidem: an update of its pharmacology, therapeutic efficacy and tolerability in the treatment of insomnia. Drugs. 2000;59(4):865-89. Abstract
Hoque R, Chesson AL Jr. Zolpidem-induced sleepwalking, sleep related eating disorder, and sleep-driving: fluorine-18-flourodeoxyglucose positron emission tomography analysis, and a literature review of other unexpected clinical effects of zolpidem. J Clin Sleep Med. 2009;5(5):471-6. Article
Krystal AD, Erman M, Zammit GK, et al. 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. Article
Lavoisy J, Zivkovic B, Benavides J, et al. Contribution of zolpidem in the management of sleep disorders. Encephale. 1992;18(4):379-92. Abstract
Mednick SC, McDevitt EA, Walsh JK, et al. The critical role of sleep spindles in hippocampal-dependent memory: a pharmacology study. J Neurosci. 2013;33(10):4494-504. Article
Moen MD, Plosker GL. Zolpidem extended-release. CNS Drugs. 2006;20(5):419-26; discussion 427-8. Abstract
Perlis ML, McCall WV, Krystal AD, Walsh JK. Long-term, non-nightly administration of zolpidem in the treatment of patients with primary insomnia. J Clin Psychiatry. 2004;65(8):1128-37. Abstract
Pergolizzi JV, Taylor R, Raffa RB, et al. Fast-Acting sublingual zolpidem for middle-of-the-night wakefulness. Sleep Disord. 2014;2014:527109. Abstract
Roth T, Hull SG, Lankford DA, et al. Low-dose sublingual zolpidem tartrate is associated with dose-related improvement in sleep onset and duration in insomnia characterized by middle-of-the-night (MOTN) awakenings. Sleep. 2008;31(9):1277-84. Article
Roth T, Soubrane C, Titeux L, et al. Efficacy and safety of zolpidem-MR: a double-blind, placebo-controlled study in adults with primary insomnia. Sleep Med. 2006;7(5):397-406. Abstract
Sanger DJ, Perrault G, Morel E, et al. The behavioral profile of zolpidem, a novel hypnotic drug of imidazopyridine structure. Physiol Behav. 1987;41(3):235-40. Abstract
Scharf MB, Roth T, Vogel GW, Walsh JK. A multicenter, placebo-controlled study evaluating zolpidem in the treatment of chronic insomnia. J Clin Psychiatry. 1994;55(5):192-9. Abstract
Shirakawa K. Pharmacological profile and clinical effect of zolpidem (Myslee tablets), a hypnotic agent. Nihon Yakurigaku Zasshi. 2002;119(2):111-8. Abstract
Suhner A, Schlagenhauf P, Höfer I, et al. Effectiveness and tolerability of melatonin and zolpidem for the alleviation of jet lag. Aviat Space Environ Med. 2001;72(7):638-46. Abstract
Swainston Harrison T, Keating GM. Zolpidem: a review of its use in the management of insomnia. CNS Drugs. 2005;19(1):65-89. Abstract
Wang PS, Bohn RL, Glynn RJ, et al. Zolpidem use and hip fractures in older people. J Am Geriatr Soc. 2001;49(12):1685-90. Abstract
21.8 Efficacy Comparisons |
Z Drugs v Benzodiazepines
Dündar Y, Dodd S, Strobl J, et al. Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis. Hum Psychopharmacol. 2004;19(5):305-22. Abstract
Hausken AM, Furu K, Skurtveit S, et al. Starting insomnia treatment: the use of benzodiazepines versus z-hypnotics. a prescription database study of predictors. Eur J Clin Pharmacol. 2009;65(3):295-301. Abstract
Hoffmann F. Benefits and risks of benzodiazepines and Z-drugs: comparison of perceptions of GPs and community pharmacists in Germany. Ger Med Sci. 2013;11:Doc10. Article
Li S, Wang C. A comparative study of imovane and estazolam treatment on sleep disturbances. Chin Med Sci J. 1995;10(1):56-8. Abstract
Rush CR. Behavioral pharmacology of zolpidem relative to benzodiazepines: a review. Pharmacol Biochem Behav. 1998;61(3):253-69. Abstract
Sanna E, Busonero F, Talani G, et al. Comparison of the effects of zaleplon, zolpidem, and triazolam at various GABA(A) receptor subtypes. Eur J Pharmacol. 2002;451(2):103-10. Abstract
Z Drug v Z Drug
Huang YS, Hsu SC, Liu SI, Chen CK. A double-blind, randomized, comparative study to evaluate the efficacy and safety of zaleplon versus zolpidem in shortening sleep latency in primary insomnia. Chang Gung Med J. 2011;34(1):50-6. Abstract
Sanna E, Busonero F, Talani G, et al. Comparison of the effects of zaleplon, zolpidem, and triazolam at various GABA(A) receptor subtypes. Eur J Pharmacol. 2002;451(2):103-10. Abstract
21.9 Pharmacology |
Drover DR. Comparative pharmacokinetics and pharmacodynamics of short-acting hypnosedatives: zaleplon, zolpidem and zopiclone. Clin Pharmacokinet. 2004;43(4):227-38. Abstract
Greenblatt DJ, Harmatz JS, von Moltke LL, et al. Comparative kinetics and dynamics of zaleplon, zolpidem, and placebo. Clin Pharmacol Ther. 1998;64(5):553-61. Abstract
Gunja N. The clinical and forensic toxicology of Z-drugs. J Med Toxicol. 2013;9(2):155-62. Article
Soldatos CR, Dikeos DG, Whitehead A. Tolerance and rebound insomnia with rapidly eliminated hypnotics: a meta-analysis of sleep laboratory studies. Int Clin Psychopharmacol. 1999;14(5):287-303. Abstract
Binding
Bioavailability
Buccal
Intranasal
Oral
Rectal
Sublingual / Buccal
Vaginal
Blockade
By other Medications
Of other Medications
Distribution
Elimination
Extended Release
Onset of Action
Time to Cmax
Duration of Action
Half Life
Immediate Release
Onset of Action
Time to Cmax
Duration of Action
Half Life
IR v ER
Interactions
Drug – Alcohol
Drug – Alternative Med
Drug – Drug
Hesse LM, von Moltke LL, Greenblatt DJ. Clinically important drug interactions with zopiclone, zolpidem and zaleplon. CNS Drugs. 2003;17(7):513-32. Abstract
Drug – Food
Drug – Tobacco
Levels
Blood
Mechanism of Action
Metabolism
First Pass
Phase I: P 450
Phase II: UDP glucuronysyl Transferase Metabolism
Pharmacogenetics
Protein Binding
Solubility
Storage in Body
Pharmacodynamics
Potency
Tolerance
Toxicity
Pharmacokinetics
21.10 Neuro Pharmacology |
Brain Loci
Endogenous Substance Interaction
Receptor Effect
Wright BT, Gluszek CF, Heldt SA. The effects of repeated zolpidem treatment on tolerance, withdrawal-like symptoms, and GABAA receptor mRNAs profile expression in mice: comparison with diazepam. Psychopharmacology (Berl). 2014;231(15):2967-79. Abstract
Affinity
Agonism
Analgesia
Antagonism
Hyperalgesia
Neuroadaptation
Potency
Reuptake Inhibition
Receptors Affected
GABAA
Dixon CL, Harrison NL, Lynch JW, Keramidas A. Zolpidem and eszopiclone prime α1β2γ2 GABAA receptors for longer duration of activity. Br J Pharmacol. 2015;172(14):3522-36. Article
Fitzgerald AC, Wright BT, Heldt SA. The behavioral pharmacology of zolpidem: evidence for the functional significance of α1-containing GABA(A) receptors. Psychopharmacology (Berl). 2014;231(9):1865-96. Abstract
Kralic JE, O’Buckley TK, Khisti RT, et al. GABA(A) receptor alpha-1 subunit deletion alters receptor subtype assembly, pharmacological and behavioral responses to benzodiazepines and zolpidem. Neuropharmacology. 2002;43(4):685-94. Abstract
Tolerance
21.11 Adverse Effects: General |
Falls / Fractures / Injuries
Wang PS, Bohn RL, Glynn RJ, et al. Zolpidem use and hip fractures in older people. J Am Geriatr Soc. 2001;49(12):1685-90. Abstract
Mortality
Gunja N. The clinical and forensic toxicology of Z-drugs. J Med Toxicol. 2013;9(2):155-62. Article
Zhang YZ, He HY, She CM, Lian J. Research Progress on Forensic Toxicology of Z-drugs. Fa Yi Xue Za Zhi. 2015;31(4):293-7. Abstract
Hospitalization
Quality of Life
21.12 Adverse Effects: By Organ System |
Atopy
Hematologic
Cancer
Immunologic
Dermatologic
HEENT
Respiratory
Maillard D, Thiercelin JF, Fuseau E, et al. Effects of zolpidem versus diazepam and placebo on breathing control parameters in healthy human subjects. Int J Clin Pharmacol Res. 1992;12(1):27-35. Abstract
Mason M, Cates CJ, Smith I. Effects of opioid, hypnotic and sedating medications on sleep-disordered breathing in adults with obstructive sleep apnea. Cochrane Database Syst Rev. 2015;7:CD011090. Abstract
Ranløv PJ, Nielsen SP. Effect of zopiclone and diazepam on ventilatory response in normal human subjects. Sleep. 1987;10 Suppl 1:40-7. Abstract
Cardiovascular
GI
GU
Gyn
Obstetric
Teratogenic Potential
Musculoskeletal
Endocrine
Neurologic
Psychiatric
McCall WV, Benca RM, Rosenquist PB, et al. Hypnotic medications and suicide: risk, mechanisms, mitigation, and the FDA. Am J Psychiatry. 2016 Sep 9:appiajp201616030336. [Epub ahead of print]. Abstract
Combined Body Systems
21.13 Adverse Effects: Executive Function – Multiple Function Studies |
Allain H, Bentué-Ferrer D, Tarral A, Gandon JM. Effects on postural oscillation and memory functions of a single dose of zolpidem 5 mg, zopiclone 3.75 mg and lormetazepam 1 mg in elderly healthy subjects. A randomized, cross-over, double-blind study versus placebo. Eur J Clin Pharmacol. 2003;59(3):179-88. Abstract
Berlin I, Warot D, Hergueta T, et al. Comparison of the effects of zolpidem and triazolam on memory functions, psychomotor performances, and postural sway in healthy subjects. J Clin Psychopharmacol. 1993;13(2):100-6. Abstract
Boyle J, Trick L, Johnsen S, et al. Next-day cognition, psychomotor function, and driving-related skills following nighttime administration of eszopiclone. Hum Psychopharmacol. 2008;23(5):385-97. Abstract
Gunja N. In the Zzz zone: the effects of Z-drugs on human performance and driving. J Med Toxicol. 2013;9(2):163-71. Article
Leufkens TR, Lund JS, Vermeeren A. Highway driving performance and cognitive functioning the morning after bedtime and middle-of-the-night use of gaboxadol, zopiclone and zolpidem. J Sleep Res. 2009;18(4):387-96. Abstract
Mets MA, de Vries JM, de Senerpont Domis LM, et al. Next-day effects of ramelteon (8 mg), zopiclone (7.5 mg), and placebo on highway driving performance, memory functioning, psychomotor performance, and mood in healthy adult subjects. Sleep. 2011;34(10):1327-34. Article
Mintzer MZ, Frey JM, Yingling JE, Griffiths RR. Triazolam and zolpidem: a comparison of their psychomotor, cognitive, and subjective effects in healthy volunteers. Behav Pharmacol. 1997;8(6-7):561-74. Abstract
Rush CR, Armstrong DL, Ali JA, Pazzaglia PJ. Benzodiazepine-receptor ligands in humans: acute performance-impairing, subject-rated and observer-rated effects. J Clin Psychopharmacol. 1998;18(2):154-65. Abstract
Rush CR, Griffiths RR. Zolpidem, triazolam, and temazepam: behavioral and subject-rated effects in normal volunteers. J Clin Psychopharmacol. 1996;16(2):146-57. Abstract
Troy SM, Lucki I, Unruh MA, et al. Comparison of the effects of zaleplon, zolpidem, and triazolam on memory, learning, and psychomotor performance. J Clin Psychopharmacol. 2000;20(3):328-37. Abstract
Verster JC, Volkerts ER, Schreuder AH, et al. Residual effects of middle-of-the-night administration of zaleplon and zolpidem on driving ability, memory functions, and psychomotor performance. J Clin Psychopharmacol. 2002;22(6):576-83. Abstract
Simpson CA, Rush CR. Acute performance-impairing and subject-rated effects of triazolam and temazepam, alone and in combination with ethanol, in humans. J Psychopharmacol. 2002;16(1):23-34. Abstract
21.14 Adverse Effects: Executive Function – Single Function Studies |
Acute
Acute Cognitive Effects
Stranks EK, Crowe SF. The acute cognitive effects of zopiclone, zolpidem, zaleplon, and eszopiclone: a systematic review and meta-analysis. J Clin Exp Neuropsychol. 2014;36(7):691-700. Abstract
Acute Cognitive Effects: Memory
Acute Psychomotor Effects
Mamelak M, Buck L, Csima A, et al. Effects of flurazepam and zopiclone on the performance of chronic insomniac patients: a study of ethanol-drug interaction. Sleep. 1987;10 Suppl 1:79-87. Abstract
Acute Psychomotor Effects: Driving
Bramness JG, Skurtveit S, Mørland J. Detection of zopiclone in many drivers – a sign of misuse or abuse. Tidsskr Nor Laegeforen. 1999;119(19):2820-1. Abstract
Gustavsen I, Al-Sammurraie M, Mørland J, Bramness JG. Impairment related to blood drug concentrations of zopiclone and zolpidem compared to alcohol in apprehended drivers. Accid Anal Prev. 2009;41(3):462-6. Abstract
Leufkens TR, Vermeeren A. Zopiclone’s residual effects on actual driving performance in a standardized test: a pooled analysis of age and sex effects in 4 placebo-controlled studies. Clin Ther. 2014;36(1):141-50. Abstract
Roth T, Eklov SD, Drake CL, Verster JC. Meta-analysis of on-the-road experimental studies of hypnotics: effects of time after intake, dose, and half-life. Traffic Inj Prev. 2014;15(5):439-45. Abstract
Rudisill TM, Zhu M, Kelley GA, et al. Medication use and the risk of motor vehicle collisions among licensed drivers: a systematic review. Accid Anal Prev. 2016;96:255-70. Abstract
Vermeeren A, Vuurman EF, Leufkens TR, et al. Residual effects of low-dose sublingual zolpidem on highway driving performance the morning after middle-of-the-night use. Sleep. 2014;37(3):489-96. Article
Verster JC, Roth T. Gender differences in highway driving performance after administration of sleep medication: a review of the literature. Traffic Inj Prev. 2012;13(3):286-92. Abstract
Chronic
Chronic Cognitive Effects
Chronic Cognitive Effects: Memory
Chronic Cognitive Effects: Memory – Dementia
Gomm W, von Holt K, Thome, F, et al. Regular benzodiazepine and Z-substance use and risk of dementia: an analysis of German claims data. J Alzheimer’s Dis. 2016;54(3):801-8. Abstract
Chronic Psychomotor Effects
Chronic Psychomotor Effects: Driving
Lai MM, Lin CC, Lin CC, Liu CS, Li TC, Kao CH. Long-term use of zolpidem increases the risk of major injury: a population-based cohort study. Mayo Clin Proc. 2014;89(5):589-594. Abstract
Gustavsen I, Bramness JG, Skurtveit S, et al. Road traffic accident risk related to prescriptions of the hypnotics zopiclone, zolpidem, flunitrazepam and nitrazepam. Sleep Med. 2008;9(8):818-22. Abstract
21.15 Adverse Effects: Non-medical Use |
Addiction
Bottlender R, Schütz C, Möller HJ, Soyka M. Zolpidem dependence in a patient with former polysubstance abuse. Pharmacopsychiatry. 1997;30(3):108. Abstract
Correas Lauffer J, Braquehais Conesa D, Barbudo Del Cura E, Ochoa Mangada E. Abuse, tolerance and dependence of zolpidem: three case reports. Actas Esp Psiquiatr. 2002;30(4):259-62. Abstract
Courtet P, Pignay V, Castelnau D, Boulenger JP. Abuse of and dependence on zolpidem: a report of seven cases. Encephale. 1999;25(6):652-7. Abstract
Liappas IA, Malitas PN, Dimopoulos NP, et al. Zolpidem dependence case series: possible neurobiological mechanisms and clinical management. J Psychopharmacol. 2003;17(1):131-5. Abstract
Shukla L, Bokka S, Shukla T, et al. Benzodiazepine and “Z-Drug” dependence: data from a tertiary care center. Prim Care Companion CNS Disord. 2017;19(1). Article
Soyka M, Bottlender R, Möller HJ. Epidemiological evidence for a low abuse potential of zolpidem. Pharmacopsychiatry. 2000;33(4):138-41. Abstract
Ströhle A, Antonijevic IA, Steiger A, Sonntag A. Dependency of non-benzodiazepine hypnotics. Two case reports. Nervenarzt. 1999;70(1):72-5. Abstract
Addiction Liability
Evans SM, Funderburk FR, Griffiths RR. Zolpidem and triazolam in humans: behavioral and subjective effects and abuse liability. J Pharmacol Exp Ther. 1990;255(3):1246-55. Abstract
Griffiths RR, Johnson MW. Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds. J Clin Psychiatry. 2005;66 Suppl 9:31-41. Abstract
Griffiths RR, Weerts EM. Benzodiazepine self-administration in humans and laboratory animals–implications for problems of long-term use and abuse. Psychopharmacology (Berl). 1997;134(1):1-37. Abstract
Hajak G, Müller WE, Wittchen HU, et al. Abuse and dependence potential for the non-benzodiazepine hypnotics zolpidem and zopiclone: a review of case reports and epidemiological data. Addiction. 2003;98(10):1371-8. Abstract
Jaffe JH, Bloor R, Crome I, et al. A postmarketing study of relative abuse liability of hypnotic sedative drugs. Addiction. 2004;99(2):165-73. Abstract
Licata SC, Mashhoon Y, Maclean RR, Lukas SE. Modest abuse-related subjective effects of zolpidem in drug-naive volunteers. Behav Pharmacol. 2011;22(2):160-6. Article
Rush CR, Baker RW, Wright K. Acute behavioral effects and abuse potential of trazodone, zolpidem and triazolam in humans. Psychopharmacology (Berl). 1999;144(3):220-33. Abstract
Soyka M, Bottlender R, Möller HJ. Epidemiological evidence for a low abuse potential of zolpidem. Pharmacopsychiatry. 2000;33(4):138-41. Abstract
Wilkinson CJ. The abuse potential of zolpidem administered alone and with alcohol. Pharmacol Biochem Behav. 1998;60(1):193-202. Abstract
Craving
Diversion
Gateway
Harmful Use
Liking
Overdose
Prevention of non-medical use
Risk factors for non-medical use
21.16 Z Drugs in Subpopulations |
Armed Services / Veterans
Addiction
Alcohol
Amphetamine
Behavioral Addictions
Benzodiazepine
Cocaine
Nicotine
Opioid
Cancer
Cardiovascular Disease
Care Facilities
Cognitive Dysfunction
Criminal Justice
Elderly
Ancoli-Israel S, Krystal AD, McCall WV, et al. A 12-week, randomized, double-blind, placebo-controlled study evaluating the effect of eszopiclone 2 mg on sleep/wake function in older adults with primary and comorbid insomnia. Sleep. 2010;33(2):225-34. Article
Hedner J, Yaeche R, Emilien G, et al. Zaleplon shortens subjective sleep latency and improves subjective sleep quality in elderly patients with insomnia. The Zaleplon Clinical Investigator Study Group. Int J Geriatr Psychiatry. 2000;15(8):704-12. Abstract
Walsh JK, Soubrane C, Roth T. Efficacy and safety of zolpidem extended release in elderly primary insomnia patients. Am J Geriatr Psychiatry. 2008;16(1):44-57. Abstract
Wang PS, Bohn RL, Glynn RJ, et al. Zolpidem use and hip fractures in older people. J Am Geriatr Soc. 2001;49(12):1685-90. Abstract
Ethnicity
African-American
Asian
Caucasian
Hispanic
Native American
Pacific Island
Health Care Providers
Hepatic Disease
HIV / AIDS
Wei HT, Chen MH, Wong WW, et al. Benzodiazepines and Z-drug use among HIV-infected patients in Taiwan: a 13-year nationwide cohort study. Biomed Res Int. 2015;2015:465726. Article
LGBT
Men
Roehrs TA, Roth T. Gender differences in the efficacy and safety of chronic nightly zolpidem. J Clin Sleep Med. 2016;12(3):319-25. Article
Pain
Goforth HW, Preud’homme XA, Krystal AD. A randomized, double-blind, placebo-controlled trial of eszopiclone for the treatment of insomnia in patients with chronic low back pain. Sleep. 2014;37(6):1053-60. Abstract
Palliative Care – End of Life
Pediatric
Psychiatric Co-Morbidities
Krystal AD, McCall WV, Fava M, et al. Eszopiclone treatment for insomnia: effect size comparisons in patients with primary insomnia and insomnia with medical and psychiatric comorbidity. Prim Care Companion CNS Disord. 2012;14(4). pii: PCC.11m01296. Article
Anxiety
Fava M, Asnis GM, Shrivastava R, et al. Zolpidem extended-release improves sleep and next-day symptoms in comorbid insomnia and generalized anxiety disorder. J Clin Psychopharmacol. 2009;29(3):222-30. Abstract
Pollack M, Kinrys G, Krystal A, et al. Eszopiclone coadministered with escitalopram in patients with insomnia and comorbid generalized anxiety disorder. Arch Gen Psychiatry. 2008;65(5):551-62. Abstract
BPD
Depression
Fava M, Asnis GM, Shrivastava RK, et al. Improved insomnia symptoms and sleep-related next-day functioning in patients with comorbid major depressive disorder and insomnia following concomitant zolpidem extended-release 12.5 mg and escitalopram treatment: a randomized controlled trial. J Clin Psychiatry. 2011;72(7):914-28. Abstract
Psychosis
Tek C, Palmese LB, Krystal AD, et al. The impact of eszopiclone on sleep and cognition in patients with schizophrenia and insomnia: a double-blind, randomized, placebo-controlled trial. Schizophr Res. 2014;160(1-3):180-5. Abstract
Suicidality
Trauma
Pulmonary Disease
Renal Disease
Sleep Disorders
Sleep Apnea
Surgical
Swallowing Disorders
Women
Roehrs TA, Roth T. Gender differences in the efficacy and safety of chronic nightly zolpidem. J Clin Sleep Med. 2016;12(3):319-25. Article
Perinatal
Nursing
