Evidence-Based Reviews

Benzodiazepines: A versatile clinical tool

Current Psychiatry. 2012 April;11(4):54-64

References

1. Mihic SJ, Harris RA. Hypnotics and sedatives. In: Brunton LL Chabner BA, Knollmann BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. New York, NY: McGraw Hill and Company; 2011:457-480.

2. Facts and comparisons Web site. 2011 Wolters Kluwer Health Inc. http://online.factsandcomparisons.com. Accessed August 16, 2011.

3. DuPont RL, Greene W, Lydiard RB. Sedatives and hypnotics: pharmacology and epidemiology. In: Gold MS Hermann R, eds. UpToDate. http://www.uptodate.com/contents/sedatives-and-hypnotics-abuse-and-dependence-pharmacology-and-epidemiology. Accessed August 16, 2011.

4. U.S. Food and Drug Administration. Orange book: approved drug products with therapeutic equivalence evaluations. http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm. Accessed August 16, 2011.

5. Chouinard G. Issues in the clinical use of benzodiazepines: potency withdrawal, and rebound. J Clin Psychiatry. 2004;65(suppl 5):7-12.

6. Shader RI, Greenblatt DJ. Can you provide a table of equivalencies for benzodiazepines and other marketed benzodiazepine receptor agonists? J Clin Psychopharmacol. 1997;17(4):331.-

7. Amato L, Minozzi S, Davoli M. Efficacy and safety of pharmacologic interventions for the treatment of the alcohol withdrawal syndrome. Cochrane Database Syst Rev. 2011;15(6):CD008537.-

8. Schutte-Rodin S, Broch L, Buysse D, et al. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2008;4(5):487-504.

9. Foral P, Dewan N, Malesker M. Insomnia: a therapeutic review for pharmacists. Consult Pharm. 2011;26(5):332-341.

10. Riemann D, Perlis ML. The treatments of chronic insomnia: a review of benzodiazepine receptor agonists and psychological and behavioral therapies. Sleep Med Rev. 2009;13(3):205-214.

11. Hidalgo RB, Tupler LA, Davidson JR. An effect-size analysis of pharmacologic treatments of generalized anxiety disorder. J Psychopharmacol. 2007;21(8):864-872.

12. Davidson JR, Zhang W, Connor KM, et al. A psychopharmacological treatment algorithm for generalised anxiety disorder (GAD). J Psychopharmacol. 2010;24(1):3-26.

13. Bandelow B, Zohar J, Hollander E, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders - first revision. World J Biol Psychiatry. 2008;9(4):248-312.

14. American Psychiatric Association. Practice guideline for the treatment of patients with panic disorder. 2nd ed. Arlington VA: American Psychiatric Publishing, Inc.; 2009.

15. Pollack MH, Simon NM, Worthington JJ, et al. Combined paroxetine and clonazepam treatment strategies compared to paroxetine monotherapy for panic disorder. J Psychopharmacol. 2003;17(3):276-282.

16. Watanabe N, Churchill R, Furukawa TA. Combined psychotherapy plus benzodiazepines for panic disorder. Cochrane Database Syst Rev. 2009;(1):CD005335.-

17. Otto MW, McHugh RK, Simon NM, et al. Efficacy of CBT for benzodiazepine discontinuation in patients with panic disorder: further evaluation. Behav Res Ther. 2010;48(8):720-727.

18. Davidson JR. Use of benzodiazepines in social anxiety disorder generalized anxiety disorder, and posttraumatic stress disorder. J Clin Psychiatry. 2004;65(suppl 5):29-33.

19. Argyropoulos SV, Sandford JJ, Nutt DJ. The psychobiology of anxiolytic drugs Part 2: pharmacological treatments of anxiety. Pharmacol Ther. 2000;88(3):213-227.

20. Connor KM, Davidson JR, Potts NL, et al. Discontinuation of clonazepam in the treatment of social phobia. J Clin Psychopharmacol. 1998;18(5):373-378.

21. Miller CH, Fleischhacker WW. Managing antipsychotic-induced acute and chronic akathisia. Drug Saf. 2000;22(1):73-81.

22. Rodnitzky RL. Drug-induced movement disorders. Clin Neuropharmacol. 2002;25(3):142-151.

23. Arbaizar B, Gómez-Acebo I, Llorca J. Postural induced tremor in psychiatry. Psychiatry Clin Neurosci. 2008;62(6):638-645.

24. Casher MI, Bess JD. Manual of inpatient psychiatry. New York NY: Cambridge University Press; 2010.

25. Battaglia J. Pharmacological management of acute agitation. Drugs. 2005;65(9):1207-1222.

26. Physicians’ desk reference. Montvale NJ: PDR Network, LLC; 2010.

27. Rosebush PI, Mazurek MF. Catatonia and its treatment. Schizophr Bull. 2010;36(2):239-242.

28. Ungvari GS, Kau LS, Wai-Kwong T, et al. The pharmacological treatment of catatonia: an overview. Eur Arch Psychiatry Clin Neurosci. 2001;251(suppl 1):I31-I34.

29. Fink M, Taylor MA. Catatonia: a clinician’s guide to diagnosis and treatment. New York NY: Cambridge University Press; 2003.

30. Naguib N, Koorn R. Interactions between psychotropics anaesthetics and electroconvulsive therapy: implications for drug choice and patient management. CNS Drugs. 2002;16(4):229-247.

31. Boylan LS, Haskett RF, Mulsant BH, et al. Determinants of seizure threshold in ECT: benzodiazepine use, anesthetic dosage, and other factors. J ECT. 2000;16(1):3-18.

32. Krystal AD, Watts BV, Weiner RD, et al. The use of flumazenil in the anxious and benzodiazepine-dependent ECT patient. J ECT. 1998;14(1):5-14.

33. Melton ST, Kirkwood CK. Anxiety disorders I: generalized anxiety panic, and social anxiety disorders. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: a pathophysiologic approach. New York, NY: McGraw-Hill Companies; 2011:1209-1228.

34. Benzodiazepine toolkit. The Pharmacist’s Letter/Prescriber’s Letter. 2011;27(4):270406.-

35. Lader M. Benzodiazepines revisited – will we ever learn? Addiction. 2011;106(12):2086-2109.

36. Toblin RL, Paulozzi LJ, Logan JE, et al. Mental illness and psychotropic drug use among prescription drug overdose deaths: a medical examiner chart review. J Clin Psychiatry. 2010;71(4):491-496.

37. Ashton H. The diagnosis and management of benzodiazepine dependence. Curr Opin Psychiatry. 2005;18(3):249-255.

38. Menon SJ. Psychotropic medication during pregnancy and lactation. Arch Gynecol Obstet. 2008;277(1):1-13.

Risks of benzodiazepine use

Clinical Point

Agents with shorter half-lives such as lorazepam and oxazepam are preferred for older patients

For most indications, benzodiazepine therapy should be short-term.³⁵ Use exceeding 2 to 4 weeks increases the risk for dependence and withdrawal. Tell patients to avoid alcohol while taking a benzodiazepine because this combination is potentially lethal. Benzodiazepines are commonly abused and abuse can lead to unintentional drug overdose. Benzodiazepines accounted for 37% of unintentional drug overdose deaths in West Virginia in 2006; in 46% of these cases, benzodiazepines were used for nonmedical purposes. Clinicians can help reduce the risk of diversion by limiting prescriptions to 30 days with no refills.³⁶

Clinical Point

Benzodiazepine use should be short-term; use exceeding 2 to 4 weeks increases the risk for dependence and withdrawal

Older patients taking benzodiazepines are at increased risk of falls and hip fractures.³⁷ Lorazepam, oxazepam, and temazepam—agents with shorter half-lives that are not greatly affected by pharmacokinetic changes associated with aging—are preferred for these patients.³⁴ Patients with dementia or other CNS-compromising conditions may become confused or delirious with regular benzodiazepine dosing. Educate patients to whom you prescribe benzodiazepines about the importance of gauging their level of sedation before driving or engaging in other tasks for which sedation could compromise their safety. Benzodiazepine use during pregnancy requires a careful discussion of risks and benefits (Box 2).³⁸

Box 2

Using benzodiazepines during pregnancy

Benzodiazepine use during pregnancy has been associated with cleft palate and urogenital and neurologic malformations in the fetus.³⁸ Although data are conflicting—particularly among recent meta-analyses that fail to demonstrate an association—some experts advise against benzodiazepine use in the first trimester. Participate in shared decision making with your patients and educate them about the potential risks and benefits of benzodiazepine use during the first trimester and throughout pregnancy. After delivery, newborns may develop “floppy baby syndrome”—which is associated with lethargy, difficulty eating, and respiratory depression—or withdrawal.³⁸ To minimize this risk, consider tapering the benzodiazepine as the patient approaches delivery.

Related Resources

Substance Abuse and Mental Health Services Administration. www.samhsa.gov.
National Institute on Drug Abuse resources for medical and health professionals. www.drugabuse.gov/medical-health-professionals.
American Academy of Sleep Medicine. www.aasmnet.org.

Drug Brand Names

Alprazolam • Xanax
Chlordiazepoxide • Librium, Limbitrol
Clonazepam • Klonopin
Clorazepate • Tranxene
Diazepam • Valium
Diphenhydramine • Benadryl, others
Estazolam • ProSom
Flumazenil • Romazicon
Flurazepam • Dalmane
Haloperidol • Haldol
Lithium • Lithobid
Lorazepam • Ativan
Olanzapine • Zyprexa
Oxazepam • Serax
Paroxetine • Paxil
Pregabalin • Lyrica
Propranolol • Inderal, InnoPran XL, others
Quazepam • Doral
Ramelteon • Rozerem
Sertraline • Zoloft
Temazepam • Restoril
Triazolam • Halcion
Valproic acid • Depakene, Stavzor, others

Disclosures

Drs. Bostwick and Yasugi report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Casher is a speaker for AstraZeneca and Sunovion Pharmaceuticals.

Clinical Point

Benzodiazepine use during pregnancy has been associated with cleft palate and urogenital and neurologic malformations