Psychotherapy and Psychosomatics

Dubovsky S.L.a,b· Marshall D.a

Author affiliations

aDepartment of Psychiatry, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA
bDepartments of Psychiatry and Medicine, University of Colorado School of Medicine, Denver, CO, USA

Log in to MyKarger to check if you already have access to this content.

Buy FullText & PDF Unlimited re-access via MyKarger Unrestricted printing, no saving restrictions for personal use read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.

Save over 20% compared to the individual article price.

Learn more

Rent/Cloud Rent for 48h to view Buy Cloud Access for unlimited viewing via different devices Synchronizing in the ReadCube Cloud Printing and saving restrictions apply Rental: USD 8.50
Cloud: USD 20.00

Select

Subscribe Access to all articles of the subscribed year(s) guaranteed for 5 years Unlimited re-access via Subscriber Login or MyKarger Unrestricted printing, no saving restrictions for personal use read more

Subcription rates

Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview

Received: December 11, 2021
Accepted: March 29, 2022
Published online: May 03, 2022

Number of Print Pages: 28
Number of Figures: 0
Number of Tables: 3

ISSN: 0033-3190 (Print)
eISSN: 1423-0348 (Online)

For additional information: https://www.karger.com/PPS

Abstract

Benzodiazepines and medications acting on benzodiazepine receptors that do not have a benzodiazepine structure (z-drugs) have been viewed by some experts and regulatory bodies as having limited benefit and significant risks. Data presented in this article support the use of these medications as treatments of choice for acute situational anxiety, chronic anxiety disorders, insomnia, alcohol withdrawal syndromes, and catatonia. They may also be useful adjuncts in the treatment of anxious depression and mania, and for medically ill patients. Tolerance develops to sedation and possibly psychomotor impairment, but not to the anxiolytic effect of benzodiazepines. Sedation can impair cognitive function in some patients, but assertions that benzodiazepines increase the risk of dementia are not supported by recent data. Contrary to popular opinion, benzodiazepines are not frequently misused or conduits to misuse of other substances in patients without substance use disorders who are prescribed these medications for appropriate indications; most benzodiazepine misuse involves medications that are obtained from other people. Benzodiazepines are usually not lethal in overdose except when ingested with other substances, especially alcohol and opioids. Benzodiazepines comprise one of the few classes of psychotropic medication the mechanisms of action of which are clearly delineated, allowing for greater precision in their clinical use. These medications, therefore, belong in the therapeutic armamentarium of the knowledgeable clinician.

© 2022 S. Karger AG, Basel

References Greenblatt DJ, Shader RI. Meprobamate: a study of irrational drug use. Am J Psychiatry. 1971 Apr;127(10):1297–303. Balon R, Starcevic V, Silberman E, Cosci F, Dubovsky SL, Fava GA, et al. The rise and fall and rise of benzodiazepines: a return of the stigmatized and repressed. Braz J Psychiatry. 2020 May–Jun;42(3):243–4. Greenblatt DJ, Harmatz JS, Shader RI. Diazepam in the elderly: looking back, ahead and at the evidence. J Clin Psychopharmacol. 2020 May–Jun;40(3):215–9. Silberman E, Balon R, Starcevic V, Shader RI, Cosci F, Fava GA, et al. Benzodiazepines: it’s time to return to the evidence. Br J Psychiatry. 2021 Mar;218(3):125–7. Greenblatt DJ, Shader RI. Drug therapy. Benzodiazepines (first of two parts). N Engl J Med. 1974 Nov;291(19):1011–5. Greenblatt DJ, Shader RI. Drug therapy. Benzodiazepines (second of two parts). N Engl J Med. 1974 Dec;291(23):1239–43. Schwartz HI. An empirical review of the impact of triplicate prescription of benzodiazepines. Hosp Community Psychiatry. 1992 Apr;43(4):382–5. Weintraub M, Singh S, Byrne L, Maharaj K, Guttmacher L. Consequences of the 1989 New York State triplicate benzodiazepine prescription regulations. NIDA Res Monogr. 1993;131:279–93. Simoni-Wastila L, Ross-Degnan D, Mah C, Gao X, Brown J, Cosler LE, et al. A retrospective data analysis of the impact of the New York triplicate prescription program on benzodiazepine use in medicaid patients with chronic psychiatric and neurologic disorders. Clin Ther. 2004 Feb;26(2):322–36. Hoffman RS, Wipfler MG, Maddaloni MA, Weisman RS. Has the New York State triplicate benzodiazepine prescription regulation influenced sedative-hypnotic overdoses? N Y State J Med. 1991 Oct;91(10):436–9. American Psychiatric Association. Task Force on Benzodiazepine Toxicity. Benzodiazepine toxicity, dependence, and abuse. Washington, DC: American Psychiatric Association; 1990. American Psychiatric Assocation. Diagnostic and Statistical Manual of Mental Disorders. 3rd ed. Washington, DC: American Psychiatric Press, Inc.; 1980. Huerta C, Abbing-Karahagopian V, Requena G, Oliva B, Alvarez Y, Gardarsdottir H, et al. Exposure to benzodiazepines (anxiolytics, hypnotics and related drugs) in seven European electronic healthcare databases: a cross-national descriptive study from the PROTECT-EU Project. Pharmacoepidemiol Drug Saf. 2016 Mar;25(Suppl 1):56–65. Rosman S, Le Vaillant M, Pelletier-Fleury N. Gaining insight into benzodiazepine prescribing in general practice in France: a data-based study. BMC Fam Pract. 2011 May;12:28. Johansen ME, Niforatos JD. Benzodiazepine use in the USA is driven by long-term users: a repeated cross-sectional study of MEPS 2002–2016. J Gen Intern Med. 2019 Dec;34(12):2717–9. Hirschtritt ME, Olfson M, Kroenke K. Balancing the risks and benefits of benzodiazepines. JAMA. 2021 Jan;325(4):347–8. Sidorchuk A, Isomura K, Molero Y, Hellner C, Lichtenstein P, Chang Z, et al. Benzodiazepine prescribing for children, adolescents, and young adults from 2006 through 2013: a total population register-linkage study. PLoS Med. 2018 Aug;15(8):e1002635. Bushnell GA, Crystal S, Olfson M. Prescription benzodiazepine use in privately insured U.S. children and adolescents. Am J Prev Med. 2019 Dec;57(6):775–85. Nicholson MW, Sweeney A, Pekle E, Alam S, Ali AB, Duchen M, et al. Diazepam-induced loss of inhibitory synapses mediated by PLCδ/Ca2+/calcineurin signalling downstream of GABAA receptors. Mol Psychiatry. 2018 Sep;23(9):1851–67. Dujardin S, Pijpers A, Pevernagie D. Prescription drugs used in insomnia. Sleep Med Clin. 2020 Jun;15(2):133–45. Iorio MT, Vogel FD, Koniuszewski F, Scholze P, Rehman S, Simeone X, et al. GABAA receptor ligands often interact with binding sites in the transmembrane domain and in the extracellular domain- can the promiscuity code be cracked? Int J Mol Sci. 2020 Jan;21(1):334. Rudolph U, Moss SJ. Modulating anxiety and activity. A regulator of inhibitory neurotransmission is essential for benzodiazepine actions. Science. 2019 Oct;366(6462):185–6. Zorumski CF, Isenberg KE. Insights into the structure and function of GABA-benzodiazepine receptors: ion channels and psychiatry. Am J Psychiatry. 1991 Feb;148(2):162–73. Tonon MC, Vaudry H, Chuquet J, Guillebaud F, Fan J, Masmoudi-Kouki O, et al. Endozepines and their receptors: structure, functions and pathophysiological significance. Pharmacol Ther. 2020 Apr;208:107386. Ravindran LN, Stein MB. The pharmacologic treatment of anxiety disorders: a review of progress. J Clin Psychiatry. 2010 Jul;71(7):839–54. Richey SM, Krystal AD. Pharmacological advances in the treatment of insomnia. Curr Pharm Des. 2011;17(15):1471–5. Moylan S, Staples J, Ward SA, Rogerson J, Stein DJ, Berk M. The efficacy and safety of alprazolam versus other benzodiazepines in the treatment of panic disorder. J Clin Psychopharmacol. 2011 Oct;31(5):647–52. Cosci F, Guidi J, Balon R, Fava GA. Clinical methodology matters in epidemiology: not all benzodiazepines are the same. Psychother Psychosom. 2015 Aug;84(5):262–4. Hill-Taylor B, Sketris IS, Gardner DM, Thompson K. Concordance with a STOPP (Screening Tool of Older Persons’ Potentially Inappropriate Prescriptions) criterion in Nova Scotia, Canada: benzodiazepine and zopiclone prescription claims by older adults with fall-related hospitalizations. J Popul Ther Clin Pharmacol. 2016;23(1):e1–12. Dyer AH, Murphy C, Lawlor B, Kennelly SP. Cognitive outcomes of long-term benzodiazepine and related drug (BZDR) use in people living with mild to moderate Alzheimer’s disease: results from NILVAD. J Am Med Dir Assoc. 2020 Feb;21(2):194–200. Ishibashi Y, Nishitani R, Shimura A, Takeuchi A, Touko M, Kato T, et al. Non-GABA sleep medications, suvorexant, as risk factors for falls: Case-control and case-crossover study. PLoS One. 2020 Sep;15(9):e0238723. Heinemann S, Brockmöller J, Hagmayer Y, Himmel W. Why Z-drugs are used even if doctors and nurses feel unable to judge their benefits and risks-a hospital survey. Eur J Clin Pharmacol. 2020 Feb;76(2):285–90. Aronson JK. Benzodiazepines. In: Aronson JK, editor. Meyler’s side effects of drugs. 16th ed. Amsterdam: Elsevier; 2016. Vol. 1; p. 863. Mihic SJ, Mayfield J, Harris RA. Hypnotics and sedatives. In: Brunton LL, Hilal-Dandan R, Knollmann BC, editors. Goodman & Gilman’s: the pharmacological basis of therapeutics. 13th ed. New York, NY: McGraw-Hill Education; 2017. Nelson LS, Howland MA, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS, editors. Goldfrank’s toxicologic emergencies. 11th ed. New York, NY: McGraw-Hill Education; 2019. Cordovilla-Guardia S, Molina TB, Franco-Antonio C, Santano-Mogena E, Vilar-López R. Association of benzodiazepines, opioids and tricyclic antidepressants use and falls in trauma patients: conditional effect of age. PLoS One. 2020 Jan;15(1):e0227696. Stewart SA. The effects of benzodiazepines on cognition. J Clin Psychiatry. 2005;66(Suppl 2):9–13. Duan Y, Wei J, Geng W, Jiang J, Zhao X, Li T, et al. The effect of short-term use of benzodiazepines on cognitive function of major depressive disorder patients being treated with antidepressants. J Affective Disord. 2019 Sep;256:1–7. Lalwani P, Garrett DD, Polk TA. Dynamic recovery: GAMA agonism restores neural variability in older, poorer performing adults. J Neurosci. 2021 Nov;41(45):9350–60. Wittenborn JR. Effects of benzodiazepines on psychomotor performance. Br J Clin Pharmacol. 1979;7(Suppl 1):61S–7S. Espinoza RT. Clarifying the relationship between benzodiazepines and dementia. J Am Med Dir Assoc. 2020 Feb;21(2):143–5. Boukrina O, Barrett AM. Disruption of the ascending arousal system and cortical attention networks in post-stroke delirium and spatial neglect. Neurosci Biobehav Rev. 2017 Dec;83:1–10. Kok L, Slooter AJ, Hillegers MH, van Dijk D, Veldhuijzen DS. Benzodiazepine use and neuropsychiatric outcomes in the ICU: a systematic review. Crit Care Med. 2018 Oct;46(10):1673–80. Dervan LA, DiGennaro JL, Farris RWD, Watson RS. Delirium in a tertiary PICU: risk factors and outcolmes. Pediatr Crit Care Med. 2020 Jan;21(1):21–32. Mody K, Kaur S, Mauer EA, Gerber LM, Greenwald BM, Silver G, et al. Benzodiazepines and development of delirium in critically ill children: estimating the causal effect. Crit Care Med. 2018 Sep;46(9):1486–91. Smith HAB, Gangopadhyay M, Goben CM, Jacobowski NL, Chestnut MH, Thompson JL, et al. Delirium and benzodiazepines associated with prolonged ICU stay in cricially ill infants and young children. Crit Care Med. 2017 Sep;45(9):1427–35. Duceppe MA, Perreault MM, Frenette AJ, Burry LD, Rico P, Lavoie A, et al. Frequency, risk factors and symptomatology of iatrogenic withdrawal from opioids and benzodiazepines in critically ill neonates, children and adults: a systematic review of clinical studies. J Clin Pharm Ther. 2019 Apr;44(2):148–56. Adams F, Fernandez F, Andersson BS. Emergency pharmacotherapy of delirium in the critically ill cancer patient. Psychosomatics. 1986 Jan;27(Suppl 1):33–8. Lonergan E, Luxenberg J, Areosa Sastre A. Benzodiazepines for delirium. Cochrane Database Syst Rev. 2009 Oct;4:CD006379. Li Y, Ma J, Jin Y, Li N, Zheng R, Mu W, et al. Benzodiazepines for treatment of patients with delirium excluding those who are cared for in an intensive care unit. Cochrane Database Syst Rev. 2020 Feb;2(2):CD012670. Tanimukai H, Tsujimoto H, Matsuda Y, Tokoro A, Kanemura S, Watanabe M, et al. Novel therapeutic strategies for delirium in patients with cancer: a preliminary study. Am J Hosp Palliat Care. 2016 Jun;33(5):456–62. Dubovsky SL. Using electroconvulsive therapy for patients with neurological disease. Hosp Community Psychiatry. 1986 Aug;37(8):819–25. Baek YH, Lee H, Kim WJ, Chung JE, Pratt N, Ellett LK, et al. Uncertain association between benzodiazepine use and the risk of dementia: a cohort study. J Am Med Dir Assoc. 2020 Feb;21(2):201–11. de Gage SB, Moride Y, Ducruet T, Kurth T, Verdoux H, Tournier M, et al. Benzodiazepine use and risk of Alzheimer’s disease: case-control study. BMJ. 2014 Sep;349:g5205. Hafdi M, Hoevenaar-Blom MP, Beishuizen CRL, van Charante EPM, Richard E, van Gool WA. Association of benzodiazepine and anticholinergic drug usage with incident dementia: a prospective cohort study of community-dwelling older adults. J Am Med Dir Assoc. 2020 Feb;21(2):188–93. Nafti M, Sirois C, Kroger E, Carmichael P, Laurin D. Is benzodiazepine use associated with risk of dementia and cognitive impairment-not dementia in older persons? The Canadian Study of Health and Aging. Ann Pharmacother. 2020 Mar;54(3):219–25. Grossi CM, Richardson K, Fox C, Maidment I, Steel N, Loke YK, et al. Anticholinergic and benzodiazepine medication use and risk of incident dementia: a UK cohort study. BMC Geriatr. 2019 Oct;19(1):276. 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 Jun;177(6):497–505. Richardson K, Mattishent K, Loke YK, Steel N, Fox C, Grossi CM, et al. History of benzodiazepine prescriptions and risk of dementia: possible bias due to prevalent users and covariate measurement timing in a nested case-control study. Am J Epidemiol. 2019 Jul;188(7):1228–36. Desmidt T, Delrieu J, Lebouvier T, Robert G, David R, Balageas AC, et al. Benzodiazepine use and brain amyloid load in nondemented older individuals: a florbetapir PET study in the Multidomain Alzheimer Preventive Trial cohort. Neurobiol Aging. 2019 Dec;84:61–9. Chung JK, Nakajima S, Shinagawa S, Pitman E, Chakravarty MM, Iwata Y, et al. Benzodiazepine use attenuates cortical beta-amloid and is not associated with progressive cognitive decline in nondemented elderly adults: a pilot study using F18-florbetapir positron emission tomography. Am J Geriatr Psychiatry. 2016 Nov;24(11):1028–39. van der Sluiszen NNJJM, Vermeeren A, Verster JC, van de Loo AJAE, van Dijken JH, Veldstra JL, et al. Driving performance and neurocognitive skills of long-term users of benzodiazepine anxiolytics and hypnotics. Hum Psychopharmacol. 2019 Nov;34(6):e2715. Hoiseth G, Austdal LE, Wilk E, Bogstrand ST, Morland J. Prevalence and concentrations of drugs in older suspected drugged drivers. Traffic Injury Prevention. 2017 Apr;18(3):231–6. Meuleners LB, Duke J, Lee AH, Palamara P, Hildebrand J, Ng JQ. Psychoactive medications and crash involvement requiring hospitalization for holder drivers: a population-based study. J Am Geriatr Soc. 2011 Sep;59(9):1575–80. Orriols L, Philip P, Moore N, Castot A, Gadegbeku B, Delorme B, et al. Benzodiazepine-like hypnotics and the associated risk of road traffic accidents. Clin Pharmacol Ther. 2011 Apr;89(4):595–601. Hoiseth G, Hjelmeland K, Morland J. A comparison of driving related skills impaired by ethanol and zopiclone. Traffic Inj Prev. 2021;22(1):26–31. Dassanayake T, Michie P, Carter G, Jones A. Effects of benzodiazepines, antidepressants and opioids on driving: a systematic review and meta-analysis of epidemiological and experimental evidence. Drug Saf. 2011 Feb;34(2):125–56. Maxwell HG, Dubois S, Weaver B, Bédard M. The additive effects of alcohol and benzodiazepines on driving. Can J Public Health. 2010 Sep-Oct;101(5):353–7. Saias T, Gallarda T. Paradoxical aggressive reactions to benzodiazepine use: a review. Encephale. 2008 Sep;34(4):330–6. Rothschild AJ. Disinhibition, amnestic reactions, and other adverse reactions secondary to triazolam: a review of the literature. J Clin Psychiatry. 1992 Dec;53 Suppl:69–79. Mancuso CE, Tanzi MG, Gabay M. Paradoxical reactions to benzodiazepines: literature review and treatment options. Pharmacotherapy. 2004 Sep;24(9):1177–85. American Society of Health-System Pharmacists. AHFS drug information 2021. Bethesda, MD: American Society of Health-System Pharmacists; 2021. Yasui N, Kondo T, Furukori H, Kaneko S, Ohkubo T, Uno T, et al. Effects of repeated ingestion of grapefruit juice on the single and multiple oral-dose pharmacokinetics and pharmacodynamics of alprazolam. Psychopharmacology. 2000 Jun;150(2):185–90. Stoehr GP, Kroboth PD, Juhl RP, Wender DB, Phillips JP, Smith RB. Effect of oral contraceptives on triazolam, temazepam, alprazolam, and lorazepam kinetics. Clin Pharmacol Ther. 1984 Nov;36(5):683–90. Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. 2015 Aug;56(8):1246–51. Yang BR, Oh IS, Li J, Jeon HL, Shin JY. Association between opioid analgesic plus benzodiazepine use and death: a case-crossover study. J Psychosom Res. 2020 Aug;135:110153. Khan NF, Bykov K, Glynn RJ, Barnett ML, Gagne JJ. Coprescription of opioids with other medications and risk of opioid overdose. Clin Pharmacol Ther. 2021 Oct;110(4):1011–7. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. DSM-5. 5th ed. Arlington, VA: American Psychiatric Association; 2013. Hackett TP, Cassem NH. Reduction of anxiety in the coronary-care unit. A controlled double-blind comparison of chlordiazepoxide and amobarbital. Curr Ther Res Clin Exp. 1972 Oct;14(10):649–56. Kuang H, Johnson JA, Mulqueen JM, Bloch MH. The efficacy of benzodiazepines as acute anxiolytics in children: a meta-analysis. Depress Anxiety. 2017 Oct;34(10):888–96. Bromfalk A, Myrberg T, Wallden J, Hultin M. Preoperative anxiety in preschool children: a randomized clinical trial comparing midazolam, clonidine and demetomidine. Paediatr Anaesth. 2021 Nov;31(11):1225–33. Offidani E, Guidi J, Tomba E, Fava GA. Efficacy and tolerability of benzodiazepines versus antidepressants in anxiety disorders: a systematic review and meta-analysis. Psychother Psychosom. 2013;82(6):355–62. Guaiana G, Barbui C, Abouhassan R. Antidepressants versus placebo for generalised anxiety disorder (GAD). Cochrane Database Syst Rev. 2018 Feb;2018(2):CD012942. Corfdir C, Pelissolo A. Bon usage des traitements medicamenteux dans les troubles anxieux. Rev Prat. 2019 Nov;69(9):981–8. Rickels K, Moeller HJ. Benzodiazepines in anxiety disorders: reassessment of usefulness and safety. World J Biol Psychiatry. 2019 Sep;20(7):514–8. Chen TR, Huang HC, Hsu JH, Ouyang WC, Lin KC. Pharmacological and psychological interventions for generalized anxiety disorder in adults: a network meta-analysis. J Psychiatr Res. 2019 Nov;118:73–83. Slee A, Nazareth I, Bondaronek P, Liu Y, Cheng Z, Freemantle N. Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis. Lancet. 2019 Feb;393(10173):768–77. Gupta AK, Bhattacharya G, Farheen SA, Funaro M, Balasubramaniam M, Young J, et al. Systematic review of benzodiazepines for anxiety disorders in late life. Ann Clin Psychiatry. 2020 May;32(2):114–27. Reinhold JA, Rickels K. Pharmacological treatment for generalized anxiety disorder in adults: an update. Expert Opin Pharmacother. 2015;16(11):1669–81. Breilmann J, Girlanda F, Guaiana G, Barbui C, Cipriani A, Castellazzi M, et al. Benzodiazepines versus placebo for panic disorder in adults. Cochrane Database Syst Rev. 2019 Mar;3(3):CD010677. Bighelli I, Castellazzi M, Cipriani A, Girlanda F, Guaiana G, Koesters M, et al. Antidepressants versus placebo for panic disorder in adults. Cochrane Database Syst Rev. 2018 Apr;4(4):CD010676. Rickels K, Schweizer E. Panic disorder: long-term pharmacotherapy and discontinuation. J Clin Psychopharmacol. 1998 Dec;18(6 Suppl 2):12S–8S. Moylan S, Giorlando F, Nordfjærn T, Berk M. The role of alprazolam for the treatment of panic disorder in Australia. Aust N Z J Psychiatry. 2012 Mar;46(3):212–24. Sheikh JI, Swales PJ. Treatment of panic disorder in older adults: a pilot study comparison of alprazolam, imipramine, and placebo. Int J Psychiatry Med. 1999 Mar;29(1):107–17. Nardi AE, Valenca AM, Freire RC, Amerin R, Levitan MN, Nacimento I, et al. Randomized, open naturalistic, acute treatment of panic disorder with clonazepam or paroxetine. J Clin Psychopharmacol. 2011 Apr;31(2):259–61. Wilkinson G, Balestrieri M, Ruggeri M, Bellantuono C. Meta-analysis of double-blind placebo-controlled trials of antidepressants and benzodiazepines for patients with panic disorders. Psychol Med. 1991 Nov;21(4):991–8. Du Y, Du B, Diao Y, Yin Z, Li J, Shu Y, et al. Comparative efficacy and acceptability of antidepressants and benzodiazepines for the treatment of panic disorder: a systematic review and network meta-analysis. Asian J Psychiatr. 2021 Jun;60:102664. Quagliato LA, Cocsi F, Shader RI, Silberman E, Starcevic V, Balon R, et al. Selective serotonin reuptake inhibitors and benzodiazepines in panic disorder: a meta-analysis of common side effects in acute treatment. J Psychopharmacol. 2019 Nov;33(11):1340–51. Gomez AF, Barthel AL, Hofmann SG. Comparing the efficacy of benzodiazepines and serotonergic anti-depressants for adults with generalized anxiety disorder: a meta-analytic review. Expert Opin Pharmacother. 2018 Jun;19(8):883–94. Shinfuku M, Kishimoto T, Uchida H, Suzuki T, Mimura M, Kikuchi T. Effectiveness and safety of long-term benzodiazepine use in anxiety disorders: a systematic review and meta-analysis. Int Clin Psychopharmacol. 2019 Sep;34(5):211–21. Nardi AE, Freire RC, Mochcovitch MD, Amrein R, Levitan MN, King AL, et al. A randomized, naturalistic, parallel-group study for the long-term treatment of panic disorder with clonazepam or paroxetine. J Clin Psychopharmacol. 2012 Feb;32(1):120–6. Gupta D, Prabhakar V, Radhakrishnan M. 5HT3 receptors: targets for new antidepressant drugs. Neurosci Biobehav Rev. 2016 May;64:311–25. Rickels K, Moeller HJ. Benzodiazepines in anxiety disorders: reassessment of usefulness and safety. World J Biol Psychiatry. 2019 Sep;20(7):514–8. Kleykamp BA, Griffiths RR, McCann UD, Smith MT, Mintzer MZ. Acute effects of zolpidem extended-release on cognitive performance and sleep in healthy males after repeated nightly use. Exp Clin Psychopharmacol. 2012 Feb;20(1):28–39. Krystal AD, Erman M, Zammit G, Soubrane C, Roth T, Group ZS. Long-term efficacy and safety of zolpidem extended-release 12.5 mg, administered 3–7 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 Jan;31(1):79–90. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. 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 Feb;13(2):307–49. Riemann D, Baglioni C, Bassetti C, Bjorvatn B, Dolenc Groselj L, Ellis JG, et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017 Dec;26(6):675–700. Rios P, Cardoso R, Morra D, Nincic V, Goodarzi Z, Farah B, et al. Comparative effectiveness and safety of pharmacological and non-pharmacological interventions for insomnia: an overview of reviews. Syst Rev. 2019 Nov;8(1):281. Carter SG, Carberry JC, Grunstein RR, Eckert DJ. Randomized trial on the effects of high-dose zopiclone on OSA severity, upper airway physiology, and alertness. Chest. 2020 Jul;158(1):374–85. Cosci F, Fava GA. When anxiety and depression coexist: the role of differential diagnosis using clinimetric criteria. Psychother Psychosom. 2021;90(5):308–17. Benasi G, Guidi J, Offidani E, Balon R, Rickels K, Fava GA. Benzodiazepines as a monotherapy in depressive disorders: a systematic review. Psychother Psychosom. 2018;87(2):65–74. Ogawa Y, Takeshima N, Hayasaka Y, Tajika A, Watanabe N, Streiner D, et al. Antidepressants plus benzodiazepines for adults with major depression. Cochrane Database Syst Rev. 2019 Jun;6(6):CD001026. Altmann H, Stahl ST, Gebara MA, Lenze EJ, Mulsant BH, Blumberger DM, et al. Coprescribed benzodiazepines in older adults receiving antidepressants for anxiety and depressive disorders: association with treatment outcomes. J Clin Psychiatry. 2020 Sep;81(6):20m13283. Furukawa TA, Streiner DL, Young LT. Antidepressant and benzodiazepine for major depression. Cochrane Database Syst Rev. 2002;1:CD001026. Dold M, Bartova L, Mendlewicz J, Souery D, Porcelli S, Zohar J, et al. Clinical correlates of augmentaion/combination treatment strategies in major depressive disorder. Acta Psychiatr Scan. 2018 May;137(5):401–12. Dold M, Bartova L, Fugger G, Mitschek MMM, Kautzky A, Frey R, et al. Add-on benzodiazepine treatment in patients with major depressive disorder – results from a European cross-sectional multicenter study. Eur Neuropsychopharmacol. 2020 Dec;41:70–80. Busch FN, Miller FT, Weiden PJ. A comparison of two adjunctive treatment strategies in acute mania. J Clin Psychiatry. 1989 Dec;50(12):453–5. Lenox RH, Newhouse PA, Creelman WL, Whitaker TM. Adjunctive treatment of manic agitation with lorazepam versus haloperidol: a double-blind study. J Clin Psychiatry. 1992 Feb;53(2):47–52. Chang CM, Wu CS, Huang YW, Chau YL, Tsai HJ. Utilization of psychopharmacological treatment among patients with newly diagnosed bipolar disorder from 2001 to 2010. J Clin Psychopharmacol. 2016 Feb;36(1):32–44. Rakofsky JJ, Dunlop BW. Treating nonspecific anxiety and anxiety disorders in patients with bipolar disorder: a review. J Clin Psychiatry. 2011 Jan;72(1):81–90. Pecknold JC, Fleury D. Alprazolam-induced manic episode in two patients with panic disorder. Am J Psychiatry. 1986 May;143(5):652–3. Perlis RH, Ostacher MJ, Miklowitz DJ, Smoller JW, Dennehy EB, Cowperthwait C, et al. Benzodiazepine use and risk of recurrence in bipolar disorder: a STEP-BD report. J Clin Psychiatry. 2010 Feb;71(2):194–200. Dold M, Li C, Tardy M, Khorsand V, Gillies D, Leucht S. Benzodiazepines for schizophrenia. Cochrane Database Syst Rev. 2012 Nov;11(11):CD006391. Dold M, Li C, Gillies D, Leucht S. Benzodiazepine augmentation of antipsychotic drugs in schizophrenia: a meta-analysis and Cochrane review of randomized controlled trials. Eur Neuropsychopharmacol. 2013 Sep;23(9):1023–33. Kishi T, Inada K, Matsui Y, Iwata N. Z-drug for schizophrenia: a systematic review and meta-analysis. Psychiatry Res. 2017 Oct;256:365–70. Medda P, Toni C, Luchini F, Mariani MG, Mauri M, Perugi G. Catatonia in 26 patients with bipolar disorder: clinical features and response to electroconvulsive therapy. Bipolar Disord. 2015 Dec;17(8):892–901. Wijemanne S, Jankovic J. Movement disorders in catatonia. J Neurol Neurosurg Psychiatry. 2015 Aug;86(8):825–32. Thamizh JS, Harshini M, Selvakumar N, Bharadwaj B, Menon V. Maintenance lorazepam for treatment of catatonic states: a case series and implications (ltr). Asian J Psychiatr. 2016 Aug;22:147–9. Oldham MA, Lee HB. Catatonia vis-a-vis delirium: the significance of recognizing catatonia in altered mental status. Gen Hosp Psychiatry. 2015 Nov–Dec;37(6):554–9. Fink M, Kellner CH, McCall WV. Optimizing ECT technique in treating catatonia. J ECT. 2016 Sep;32(3):149–50. Ungvari GS, Chiu HF, Chow LY, Lau BS, Tang WK. Lorazepam for chronic catatonia: a randomized, double-blind, placebo-controlled cross-over study. Psychopharmacology. 1999 Mar;142(4):393–8. Lin CC, Hung YY, Tsai MC, Huang TL. Relapses and recurrences of catatonia: 30-case analysis and literature review. Compr Psychiatry. 2016 Apr;66:157–65. Tuerlings JH, van Waarde JA, Verwey B. A retrospective study of 34 catatonic patients: analysis of clinical care and treatment. Gen Hosp Psychiatry. 2010 Nov–Dec;32(6):631–5. Lahutte B, Cornic F, Bonnot O, Consoli A, An-Gourfinkel I, Amoura Z, et al. Multidisciplinary approach to organic catatonia in children and adolescents may improve treatment decision making. Progr Neuropsychopharmacol Biol Psychiatry. 2008 Aug;32(6):1393–8. Dhossche DM, Wachtel LE. Catatonia is hidden in plain sight among different pediatric disorders: a review article. Pediatr Neurol. 2010 Nov;43(5):307–15. Kakooza-Mwesige A, Wachtel LE, Dhossche DM. Catatonia in autism: implications across the life span. Eur Child Adolesc Psychiatry. 2008 Sep;17(6):327–35. Ohi K, Kuwata A, Shimada T, Yasuyama T, Nitta Y, Uehara T, et al. Response to benzodiazepines and the clinical course in malignant catatonia associated with schizophrenia: a case report. Medicine. 2017 Apr;96(16):e6566. Narayanaswamy JC, Tibrewal P, Zutshi A, Srinivasaraju R, Math SB. Clinical predictors of response to treatment in catatonia. Gen Hosp Psychiatry. 2012 May–Jun;34(3):312–6. Beach SR, Gomez-Bernal F, Huffman JC, Fricchione GL. Alternative treatment strategies for catatonia: a systematic review. Gen Hosp Psychiatry. 2017 Sep;48:1–19. Balon R, Sonino N, Rafanelli C. Benzodiazepines’ role in managing gastrointestinal disorders. Psychother Psychosom. 2021;90(2):81–4. Jambrek MJ, Auteri M, Serio R, Vlainic J. GABAergic system in action: connection to gastrointestinal stress-related disorders. Curr Pharm Des. 2017;23(27):4003–11. Balon R, Rafanelli C, Sonino N. Benzodiazepines: a valuable tool in the management of cardiovascular conditions. Psychother Psychosom. 2018;87(6):327–30. Fiore M, Torretta G, Passavanti MB, Sansone P, Pace MC, Alfieri A, et al. Dexmedetomidine as adjunctive therapy for the treatment of alcohol withdrawal syndrome: a systematic review protocol. JBL Database System Rev Implement Rep. 2019 Oct;17(10):2159–64. Smith DE, Wesson DR. Phenobarbital technique for treatment of barbiturate dependence. Arch Gen Psychiatry. 1971 Jan;24(1):56–60. Amato L, Minozzi S, Vecchi S, Davoli M. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev. 2010 Mar;3:CD005063.