Insomnia and related sleep disorders (somnipathies) affect a large segment of the population, and result in a significant negative impact on quality of life and reduced or lost productivity. The speed of sleep onset is a critical characteristic of successful pharmacotherapeutic intervention for insomnia. Zolpidem, a non-benzodiazepine benzodiazepine receptor agonist (nBzRA) is widely used to treat insomnia. Although not itself a benzodiazepine (BZD), zolpidem has high binding affinity for the benzodiazepine receptor, which acts as a positive allosteric modulator of the GABAA receptor complex. It therefore increases the neuronal transmembrane influx of Cl - ions, thereby decreasing neuronal excitability and promoting sleep. In this four-way crossover, dose-ranging, multiple-treatment study, a lingual spray formulation of zolpidem was safe and well - tolerated and yielded more rapid pharmacokinetics (mean plasma concentration) and efficacy (visual analog scale and digit symbol substitution test) compared to oral tablets.
National Institutes of H. (2005) National Institutes of Health State of the Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults, June 13-15, 2005. Sleep, 28, 1049-1057. https://doi.org/10.1093/sleep/28.9.1049
Benca, R.M. (2001) Consequences of Insomnia and Its Therapies. Journal of Clinical Psychiatry, 62, 33-38.
Bramoweth, A.D. and Taylor, D.J. (2012) Chronic Insomnia and Health Care Utilization in Young Adults. Behavioral Sleep Medicine, 10, 106-121. https://doi.org/10.1080/15402002.2011.587067
Agargün, M.Y., Kara, H. and Solmaz, M. (1997) Sleep Disturbances and Suicidal Behavior in Patients with Major Depression. Journal of Clinical Psychiatry, 58, 249-251. https://doi.org/10.4088/JCP.v58n0602
McCall, W.V., et al. (2010) Insomnia Severity Is an Indicator of Suicidal Ideation during a Depression Clinical Trial. Sleep Medicine, 11, 822-827. https://doi.org/10.1016/j.sleep.2010.04.004
Norra, C., Richter, N. and Juckel, G. (2011) Sleep Disturbances and Suicidality: A Common Association to Look for in Clinical Practise and Preventive Care. EPMA Journal, 2, 295-307. https://doi.org/10.1007/s13167-011-0101-2
Spiegel, K., Tasali, E., Leproult, R. and Van Cauter, E. (2009) Effects of Poor and Short Sleep on Glucose Metabolism and Obesity Risk. Nature Reviews Endocrinology, 5, 253-261. https://doi.org/10.1038/nrendo.2009.23
Hublin, C., Partinen, M., Koskenvuo, M. and Kaprio, J. (2011) Heritability and Mortality Risk of Insomnia-Related Symptoms: A Genetic Epidemiologic Study in a Population-Based Twin Cohort. Sleep, 34, 957-964. https://doi.org/10.5665/SLEEP.1136
Fava, M., et al. (2009) Zolpidem Extended-Release Improves Sleep and Next-Day Symptoms in Comorbid Insomnia and Generalized Anxiety Disorder. Journal of Clinical Psychopharmacology, 29, 222-230. https://doi.org/10.1097/JCP.0b013e3181a390ba
Pollack, M., et al. (2008) Eszopiclone Coadministered with Escitalopram in Patients with Insomnia and Comorbid Generalized Anxiety Disorder. Archives of General Psychiatry, 65, 551-562. https://doi.org/10.1001/archpsyc.65.5.551
Roth, T., et al. (2009) The Effect of Eszopiclone in Patients with Insomnia and Coexisting Rheumatoid Arthritis: A Pilot Study. Prim Care Companion Journal of Clinical Psychiatry, 11, 292-301. https://doi.org/10.4088/PCC.08m00749bro
Buysse, D.J. (2008) Chronic Insomnia. American Journal of Psychiatry, 165, 678-686. https://doi.org/10.1176/appi.ajp.2008.08010129
Morin, C.M., et al. (2009) Cognitive Behavioral Therapy, Singly and Combined with Medication, for Persistent Insomnia: A Randomized Controlled Trial. JAMA, 301, 2005-2015. https://doi.org/10.1001/jama.2009.682
Riemann, D., et al. (2011) Chronic Insomnia: Clinical and Research Challenges—An Agenda. Pharmacopsychiatry, 44, 1-14.
Yang, C.M., Lin, S.C. and Cheng, C.P. (2013) Transient Insomnia versus Chronic Insomnia: A Comparison Study of Sleep-Related Psychological/Behavioral Characteristics. Journal of Clinical Psychology, 69, 1094-1107. https://doi.org/10.1002/jclp.22000
Stepanski, E., Zorick, F., Roehrs, T., Young, D. and Roth, T. (1988) Daytime Alertness in Patients with Chronic Insomnia Compared with Asymptomatic Control Subjects. Sleep, 11, 54-60. https://doi.org/10.1093/sleep/11.1.54
Bonnet, M.H. and Arand, D.L. (1995) 24-Hour Metabolic Rate in Insomniacs and Matched Normal Sleepers. Sleep, 18, 581-588. https://doi.org/10.1093/sleep/18.7.581
Pinto, L.R., et al. (2010) New Guidelines for Diagnosis and Treatment of Insomnia. Arquivos de Neuro-Psiquiatria, 68, 666-675. https://doi.org/10.1590/S0004-282X2010000400038
Arroll, B., et al. (2012) Prevalence of Causes of Insomnia in Primary Care: A Cross-Sectional Study. British Journal of General Practice, 62, e99-e103. https://doi.org/10.3399/bjgp12X625157
Pearson, N.J., Johnson, L.L. and Nahin, R.L. (2006) Insomnia, Trouble Sleeping, and Complementary and Alternative Medicine: Analysis of the 2002 National Health Interview survey Data. Archives of Internal Medicine, 166, 1775-1782. https://doi.org/10.1001/archinte.166.16.1775
Vgontzas, A.N., et al. (2001) Chronic Insomnia Is Associated with Nyctohemeral Activation of the Hypothalamic-Pituitary-Adrenal Axis: Clinical Implications. The Journal of Clinical Endocrinology & Metabolism, 86, 3787-3794. https://doi.org/10.1210/jc.86.8.3787
Roth, T., Roehrs, T. and Pies, R. (2007) Insomnia: Pathophysiology and Implications for Treatment. Sleep Medicine Reviews, 11, 71-79. https://doi.org/10.1016/j.smrv.2006.06.002
Lie, J.D., Tu, K.N., Shen, D.D. and Wong, B.M. (2015) Pharmacological Treatment of Insomnia. PT, 40, 759-771.
Asnis, G.M., Caneva, E. and Henderson, M.A. (2016) A Review of Antidepressant-Induced Urinary Hesitancy: A Focus on Levomilnacipran ER Including Two Case Presentations (5633). Expert Opinion on Drug Safety, 15, 717-725. https://doi.org/10.1517/14740338.2016.1164138
Schutte-Rodin, S., Broch, L., Buysse, D., Dorsey, C. and Sateia, M. (2008) Clinical Guideline for the Evaluation and Management of Chronic Insomnia in Adults. Journal of Clinical Sleep Medicine, 4, 487-504.
Möhler, H. (2006) GABAA Receptors in Central Nervous System Disease: Anxiety, Epilepsy, and Insomnia. Journal of Receptor and Signal Transduction Research, 26, 731-740. https://doi.org/10.1080/10799890600920035
Gerashchenko, D., et al. (2008) Identification of a Population of Sleep-Active Cerebral Cortex Neurons. Proceedings of the National Academy of Sciences of the United States of America, 105, 10227-10232. https://doi.org/10.1073/pnas.0803125105
Winsky-Sommerer, R. (2009) Role of GABAA Receptors in the Physiology and Pharmacology of Sleep. European Journal of Neuroscience, 29, 1779-1794. https://doi.org/10.1111/j.1460-9568.2009.06716.x
Morin, A.K., Jarvis, C.I. and Lynch, A.M. (2007) Therapeutic Options for Sleep-Maintenance and Sleep-Onset Insomnia. Pharmacotherapy, 27, 89-110. https://doi.org/10.1592/phco.27.1.89
Passarella, S. and Duong, M.T. (2008) Diagnosis and Treatment of Insomnia. American Journal of Health-System Pharmacy, 65, 927-934. https://doi.org/10.2146/ajhp060640
Holbrook, A.M., Crowther, R., Lotter, A., Cheng, C. and King, D. (2000) Meta-Analysis of Benzodiazepine Use in the Treatment of Insomnia. CMAJ, 162, 225-233.
Longo, L.P. and Johnson, B. (2000) Addiction: Part I. Benzodiazepines—Side Effects, Abuse Risk and Alternatives. American Family Physician, 61, 2121-2128.
American Geriatrics Society Beers Criteria Update Expert, P. (2012) American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Journal of the American Geriatrics Society, 60, 616-631. https://doi.org/10.1111/j.1532-5415.2012.03923.x
Patat, A., et al. (1994) EEG Profile of Intravenous Zolpidem in Healthy Volunteers. Psychopharmacology, 114, 138-146. https://doi.org/10.1007/BF02245455
Garrigou-Gadenne, D., et al. (1989) Pharmacokinetics, Brain Distribution and Pharmaco-Electrocorticographic Profile of Zolpidem, a New Hypnotic, in the Rat. Journal of Pharmacology and Experimental Therapeutics, 248, 1283-1288.
Kryger, M.H., Steljes, D., Pouliot, Z., Neufeld, H. and Odynski, T. (1991) Subjective versus Objective Evaluation of Hypnotic Efficacy: Experience with Zolpidem. Sleep, 14, 399-407. https://doi.org/10.1093/sleep/14.5.399
Monti, J.M. (1989) Effect of Zolpidem on Sleep in Insomniac Patients. European Journal of Clinical Pharmacology, 36, 461-466. https://doi.org/10.1007/BF00558070
Nicholson, A.N. and Pascoe, P.A. (1986) Hypnotic Activity of an Imidazo-Pyridine (Zolpidem). British Journal of Clinical Pharmacology, 21, 205-211. https://doi.org/10.1111/j.1365-2125.1986.tb05176.x
Balkin, T.J., O’Donnell, V.M., Wesensten, N., McCann, U. and Belenky, G. (1992) Comparison of the Daytime Sleep and Performance Effects of Zolpidem versus Triazolam. Psychopharmacology, 107, 83-88. https://doi.org/10.1007/BF02244970
Bensimon, G., et al. (1990) Daytime Wakefulness Following a Bedtime Oral Dose of Zolpidem 20 mg, Flunitrazepam 2 mg and Placebo. British Journal of Clinical Pharmacology, 30, 463-469. https://doi.org/10.1111/j.1365-2125.1990.tb03798.x
Brunner, D.P., Dijk, D.J., Munch, M. and Borbely, A.A. (1991) Effect of Zolpidem on Sleep and Sleep EEG Spectra in Healthy Young Men. Psychopharmacology, 104, 1-5. https://doi.org/10.1007/BF02244546
Fairweather, D.B., Kerr, J.S. and Hindmarch, I. (1992) The Effects of Acute and Repeated Doses of Zolpidem on Subjective Sleep, Psychomotor Performance and Cognitive Function in Elderly Volunteers. European Journal of Clinical Pharmacology, 43, 597-601. https://doi.org/10.1007/BF02284957
Merlotti, L., et al. (1989) The Dose Effects of Zolpidem on the Sleep of Healthy Normals. Journal of Clinical Psychopharmacology, 9, 9-14. https://doi.org/10.1097/00004714-198902000-00003
Lader, M. (1992) Rebound Insomnia and Newer Hypnotics. Psychopharmacology, 108, 248-255. https://doi.org/10.1007/BF02245108
Dunne, S., Shannon, B., Dunne, C. and Cullen, W. (2013) A Review of the Differences and Similarities between Generic Drugs and Their Originator Counterparts, Including Economic Benefits Associated with Usage of Generic Medicines, Using Ireland as a Case Study. BMC Pharmacology and Toxicology, 14, 1. https://doi.org/10.1186/2050-6511-14-1
Andrade, C. (2015) Bioequivalence of Generic Drugs: A Simple Explanation for a US Food and Drug Administration Requirement. Journal of Clinical Psychiatry, 76, e742-e744. https://doi.org/10.4088/JCP.15f10094
Li, C.T., et al. (2016) Pharmacokinetics of a Novel Zolpidem Nasal Spray for Rapid Management of Insomnia: First Trial in Humans. Journal of Clinical Sleep Medicine, 12, 1453-1459. https://doi.org/10.5664/jcsm.6264
Neubauer, D.N. (2010) ZolpiMist: A New Formulation of Zolpidem Tartrate for the Short-Term Treatment of Insomnia in the US. Nature and Science of Sleep, 2, 79-84. https://doi.org/10.2147/NSS.S6431