Benzodiazepines and z-drugs - between treatment effectiveness and the risk of addiction
DOI:
https://doi.org/10.12775/JEHS.2023.46.01.032Keywords
benzodiazepines, Z-drugs, insomniaAbstract
Benzodiazepines (BZDs) and Z-drugs are commonly prescribed medications for anxiety and sleep disorders. This review examines their efficacy, associated risks, and alternative treatment options. BZDs enhance the activity of gamma-aminobutyric acid (GABA), reducing anxiety, while Z-drugs selectively target GABA-A receptors' alpha-1 subunits for sedative effects. Despite their effectiveness, both drug classes carry the risk of addiction, physical and psychological dependence, and withdrawal symptoms. Side effects, such as drowsiness, dizziness, and cognitive impairment, are also associated with their use. Recent studies indicate that chronic use of BZDs and Z-drugs may lead to cognitive impairment and an increased risk of dementia in older adults. Furthermore, individual factors, dosage, duration of use, and drug interactions can affect their efficacy. Prescribing trends show a decline in benzodiazepine prescriptions and an increase in Z-drug use due to perceived safety advantages. However, evidence suggests that Z-drugs carry similar risks of adverse effects and addiction potential as benzodiazepines. Healthcare professionals should carefully assess patients before prescribing these drugs and monitor their use to prevent dependence and addiction. Brief interventions, patient education, drug withdrawal support, and cognitive behavioral therapy have shown effectiveness in reducing long-term benzodiazepine and Z-drug use. Alternative treatments, including cognitive behavioral therapy and relaxation techniques, should be considered, particularly for patients with a history of addiction or those at high risk of addiction. In conclusion, the risk of addiction, withdrawal symptoms, and adverse effects associated with benzodiazepines and Z-drugs necessitates cautious prescribing and the exploration of alternative treatment options.
References
Bénard-Laribière A, Noize P, Pambrun E, Bazin F, Verdoux H, Tournier M, Bégaud B, Pariente A. [Trends in incident use of benzodiazepines and Z-drugs in France from 2006 to 2012: a population-based study]. Pharmacoepidemiol Drug Saf. 2017; 26(2):162-169. doi: 10.1002/pds.4123.
Brandt J, Leong C. [Benzodiazepines and Z-Drugs: An Updated Review of Major Adverse Outcomes Reported on in Epidemiologic Research]. Drugs R D. 2017; 17(4):493-507. doi: 10.1007/s40268-017-0207-7.
López-Muñoz F, Alamo C, García-García P. [The discovery of chlordiazepoxide and the clinical introduction of benzodiazepines: half a century of anxiolytic drugs]. J Anxiety Disord. 2011; 25(4):554-62. doi: 10.1016/j.janxdis.2011.01.002.
Hein M, Hubain P, Linkowski P, Loas G. [Prise en charge de l'insomnie: Recommandations pour la pratique en médecine générale. Support for insomnia: Recommendations for practice in general medicine]. Rev Med Brux. 2016; 37(4):235-241. French. PMID: 28525221.
Osler M, Jørgensen MB. [Associations of Benzodiazepines, Z-Drugs, and Other Anxiolytics With Subsequent Dementia in Patients With Affective Disorders: A Nationwide Cohort and Nested Case-Control Study]. Am J Psychiatry. 2020; 177(6):497-505. doi: 10.1176/appi.ajp.2019.19030315.
Richardson K, Loke YK, Fox C, Maidment I, Howard R, Steel N, Arthur A, Boyd PJ, Aldus C, Ballard C, Savva GM. [Adverse effects of Z-drugs for sleep disturbance in people living with dementia: a population-based cohort study]. BMC Med. 2020; 18(1):351. doi: 10.1186/s12916-020-01821-5.
Monti JM, Spence DW, Buttoo K, Pandi-Perumal SR. [Zolpidem's use for insomnia]. Asian J Psychiatr. 2017; 25:79-90. doi: 10.1016/j.ajp.2016.10.006.
Monti JM, Spence DW, Buttoo K, Pandi-Perumal SR. [Zolpidem's use for insomnia]. Asian J Psychiatr. 2017; 25:79-90. doi: 10.1016/j.ajp.2016.10.006.
Pollmann AS, Murphy AL, Bergman JC, Gardner DM. [Deprescribing benzodiazepines and Z-drugs in community-dwelling adults: a scoping review]. BMC Pharmacol Toxicol. 2015; 16:19. doi: 10.1186/s40360-015-0019-8.
Sirdifield C, Chipchase SY, Owen S, Siriwardena AN. [A Systematic Review and Meta-Synthesis of Patients' Experiences and Perceptions of Seeking and Using Benzodiazepines and Z-Drugs: Towards Safer Prescribing. Patient]. 2017; 10(1):1-15. doi: 10.1007/s40271-016-0182-z.
Agravat, A. [‘Z’-hypnotics versus benzodiazepines for the treatment of insomnia]. Prog. Neurol. Psychiatry, 2018; 22: 26-29. doi: 10.1002/pnp.502.
Wang X, Zhang T, Ekheden I, Chang Z, Hellner C, Jan Hasselström, Jayaram-Lindström N, M D'Onofrio B, Larsson H, Mataix-Cols D, Sidorchuk A. [Prenatal exposure to benzodiazepines and Z-drugs in humans and risk of adverse neurodevelopmental outcomes in offspring: A systematic review]. Neurosci Biobehav Rev. 2022; 137:104647. doi: 10.1016/j.neubiorev.2022.104647.
Panes A, Pariente A, Bénard-Laribière A, Lassalle R, Dureau-Pournin C, Lorrain S, Tournier M, Fourrier-Réglat A. [Use of benzodiazepines and z-drugs not compliant with guidelines and associated factors: a population-based study]. Eur Arch Psychiatry Clin Neurosci. 2020; 270(1):3-10. doi: 10.1007/s00406-018-0966-3.
Hirschtritt ME, Olfson M, Kroenke K. [Balancing the Risks and Benefits of Benzodiazepines]. JAMA. 2021; 325(4):347-348. doi: 10.1001/jama.2020.22106.
Matheson E, Hainer BL. [Insomnia: Pharmacologic Therapy]. Am Fam Physician. 2017; 96(1):29-35. PMID: 28671376.
Fang H, Tu S, Sheng J, Shao A. [Depression in sleep disturbance: A review on a bidirectional relationship, mechanisms and treatment]. J Cell Mol Med. 2019; 23(4):2324-2332. doi: 10.1111/jcmm.14170.
Baldwin DS, Aitchison K, Bateson A, Curran HV, Davies S, Leonard B, Nutt DJ, Stephens DN, Wilson S. [Benzodiazepines: risks and benefits. A reconsideration]. J Psychopharmacol. 2013; 27(11):967-71. doi: 10.1177/0269881113503509.
Dündar Y, Boland A, Strobl J, Dodd S, Haycox A, Bagust A, Bogg J, Dickson R, Walley T. [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. doi: 10.3310/hta8240.
Holbrook AM. [Treating insomnia]. BMJ. 2004; 329(7476):1198-9. doi: 10.1136/bmj.329.7476.1198.
Hajak G, Müller WE, Wittchen HU, Pittrow D, Kirch W. [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. doi: 10.1046/j.1360-0443.2003.00491.x.
Siriwardena AN, Qureshi MZ, Dyas JV, Middleton H, Orner R. [Magic bullets for insomnia? Patients' use and experiences of newer (Z drugs) versus older (benzodiazepine) hypnotics for sleep problems in primary care]. Br J Gen Pract. 2008; 58(551):417-22. doi: 10.3399/bjgp08X299290.
Vermeeren A. [Residual effects of hypnotics: epidemiology and clinical implications]. CNS Drugs. 2004; 18(5):297-328. doi: 10.2165/00023210-200418050-00003.
Kripke DF. [Greater incidence of depression with hypnotic use than with placebo]. BMC Psychiatry. 2007; 7:42. doi: 10.1186/1471-244X-7-42.
Madry MM, Kraemer T, Baumgartner MR. [Large scale consumption monitoring of benzodiazepines and z-drugs by hair analysis]. J Pharm Biomed Anal. 2020; 183:113151. doi: 10.1016/j.jpba.2020.113151.
Mokhar A, Kuhn S, Topp J, Dirmaier J, Härter M, Verthein U. [Long-term use of benzodiazepines and Z drugs: a qualitative study of patients' and healthcare professionals' perceptions and possible levers for change]. BJGP Open. 2019; 3(1):bjgpopen18X101626. doi: 10.3399/bjgpopen18X101626.
Guerlais M, Grall-Bronnec M, Feuillet F, Gérardin M, Jolliet P, Victorri-Vigneau C. [Dependence on prescription benzodiazepines and Z-drugs among young to middle-aged patients in France]. Subst Use Misuse. 2015; 50(3):320-7. doi: 10.3109/10826084.2014.980952.
Lombardi N, Bettiol A, Crescioli G, Ravaldi C, Bonaiuti R, Venegoni M, Vighi GD, Mugelli A, Mannaioni G, Vannacci A; MEREAFaPS Study group. [Risk of hospitalisation associated with benzodiazepines and z-drugs in Italy: a nationwide multicentre study in emergency departments]. Intern Emerg Med. 2020; 15(7):1291-1302. doi: 10.1007/s11739-020-02339-7.
Hockenhull J, Black JC, Haynes CM, Rockhill K, Dargan PI, Dart RC, Wood DM. [Nonmedical use of benzodiazepines and Z-drugs in the UK]. Br J Clin Pharmacol. 2021; 87(4):1676-1683. doi: 10.1111/bcp.14397.
Lynch T, Ryan C, Hughes CM, Presseau J, van Allen ZM, Bradley CP, Cadogan CA. [Brief interventions targeting long-term benzodiazepine and Z-drug use in primary care: a systematic review and meta-analysis]. Addiction. 2020; 115(9):1618-1639. doi: 10.1111/add.14981.
Curado DF, de Barros VV, Noto AR, Opaleye ES. [Dependence on hypnotics: a comparative study between chronic users of benzodiazepines and Z-drugs]. Braz J Psychiatry. 2022; 44(3):248-256. doi: 10.1590/1516-4446-2020-1651.
Victorri-Vigneau C, Dailly E, Veyrac G, Jolliet P. [Evidence of zolpidem abuse and dependence: results of the French Centre for Evaluation and Information on Pharmacodependence (CEIP) network survey]. Br J Clin Pharmacol. 2007; 64(2):198-209. doi: 10.1111/j.1365-2125.2007.02861.x.
Rush CR. [Behavioral pharmacology of zolpidem relative to benzodiazepines: a review]. Pharmacol Biochem Behav. 1998; 61(3):253-69. doi: 10.1016/s0091-3057(98)00102-6.
Zeichner SB, Zeichner RL, Gogineni K, Shatil S, Ioachimescu O. Cognitive [Behavioral Therapy for Insomnia, Mindfulness, and Yoga in Patients With Breast Cancer with Sleep Disturbance: A Literature Review]. Breast Cancer (Auckl). 2017; 11:1178223417745564. doi: 10.1177/1178223417745564.
Everitt H, McDermott L, Leydon G, Yules H, Baldwin D, Little P. [GPs' management strategies for patients with insomnia: a survey and qualitative interview study]. Br J Gen Pract. 2014; 64(619):e112-9. doi: 10.3399/bjgp14X677176. PMID: 24567616; PMCID: PMC3905408.
MacLeod S, Musich S, Kraemer S, Wicker E. [Practical non-pharmacological intervention approaches for sleep problems among older adults]. Geriatr Nurs. 2018; 39(5):506-512. doi: 10.1016/j.gerinurse.2018.02.002.
Sarris J, Panossian A, Schweitzer I, Stough C, Scholey A. [Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence]. Eur Neuropsychopharmacol. 2011; 21(12):841-60. doi: 10.1016/j.euroneuro.2011.04.002.
Ceuterick M, Christiaens T, Creupelandt H, Bracke P. [And they slept happily ever after: Online interpretive repertoires on the use of benzodiazepines and z-drugs]. Health (London). 2021: 13634593211060770. doi: 10.1177/13634593211060770.
Umbricht, A., Velez, M.L. (2021). [Benzodiazepine and Nonbenzodiazepine Hypnotics (Z-Drugs): The Other Epidemic]. In: el-Guebaly, N., Carrà, G., Galanter, M., Baldacchino, A.M. (eds) Textbook of Addiction Treatment. Springer, Cham. doi: 10.1007/978-3-030-36391-8_11
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Justyna Cabaj, Julia Bargieł, Ewelina Soroka
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 718
Number of citations: 0