Evidence-Based Reviews

Benzodiazepines: Sensible prescribing in light of the risks

Current Psychiatry. 2018 February;17(2):22-27

References

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12. American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/ocd.pdf. Published July 2007. Accessed May 3, 2017.
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15. Ciccone DS, Just N, Bandilla EB, et al. Psychological correlates of opioid use in patients with chronic nonmalignant pain: a preliminary test of the downhill spiral hypothesis. J Pain Symptom Manage. 2000;20(3):180-192.
16. Vozoris NT, Fischer HD, Wang X, et al. Benzodiazepine drug use and adverse respiratory outcomes among older adults with COPD. Eur Respir J. 2014;44(2):332-340.
17. Obiora E, Hubbard R, Sanders RD, et al. The impact of benzodiazepines on occurrence of pneumonia and mortality from pneumonia: a nested case-control and survival analysis in a population-based cohort. Thorax. 2013;68(2):163-170.
18. Taipale H, Tolppanen AM, Koponen M, et al. Risk of pneumonia associated with incident benzodiazepine use among community-dwelling adults with Alzheimer disease. CMAJ. 2017;189(14):E519-E529.
19. Iqbal MM, Sobhan T, Ryals T. Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant. Psychiatric Serv. 2002;53:39-49.
20. U.S. National Library of Medicine, TOXNET Toxicology Data Network. Lactmed: alprazolam. http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+lactmed:@term+@DOCNO+335. Accessed May 3, 2017.
21. American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2015;63(11):2227-2246.
22. Ray WA, Thapa PB, Gideon P. Benzodiazepines and the risk of falls in nursing home residents. J Am Geriatr Soc. 2000;48(6):682-685.
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26. Lagnaoui R, Tournier M, Moride Y, et al. The risk of cognitive impairment in older community-dwelling women after benzodiazepine use. Age Ageing. 2009;38(2):226-228.
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28. Olfson M, King M, Schoenbaum M. Benzodiazepine use in the United States. JAMA Psychiatry. 2015;72(2):136-142.
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30. Maust DT, Blow FC, Wiechers IR, et al. National trends in antidepressant, benzodiazepine, and other sedative-hypnotic treatment of older adults in psychiatric and primary care. J Clin Psychiatry. 2017;78(4):e363-e371.
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Pregnancy and breastfeeding. Benzodiazepines carry risks for women who are pregnant or breastfeeding. Benzodiazepine use during pregnancy may increase the relative risk of major malformations and oral clefts. It also may result in neonatal lethargy, sedation, and weight loss. Benzodiazepine withdrawal symptoms can occur in the neonate.¹⁹ Benzodiazepines are secreted in breast milk and can result in sedation among breastfed infants.²⁰

Geriatric patients. Older adults may be particularly vulnerable to the adverse effects of benzodiazepines. The Beers Criteria for Potentially Inappropriate Medication Use in Older Adults recommends against prescribing benzodiazepines to geriatric patients.²¹ Benzodiazepine use has been associated with an increased risk for falls among older adults,^22,23 with an increased risk of fractures²⁴ that can be fatal.²⁵ Benzodiazepines also have been associated with an increased risk of cognitive dysfunction and dementia.^26,27 Despite the documented risks of using benzodiazepines in geriatric patients, benzodiazepines continue to be frequently prescribed to this age group.^28,29 One study found that the rate of prescribing benzodiazepines by primary care physicians increased from 2003 to 2012, primarily among older adults with no diagnosis of pain or a psychiatric disorder.³⁰

Mortality. Benzodiazepine use also carries an increased risk of mortality. Benzodiazepine users are at increased risk of motor vehicle accidents because of difficulty maintaining road position.³¹ Some research has shown that patients with schizophrenia treated with benzodiazepines have an increased risk of death compared with those who are prescribed antipsychotics or antidepressants.³² Another study showed that patients with schizophrenia who were prescribed benzodiazepines had a greater risk of death by suicide and accidental poisoning.³³ Benzodiazepine use has been associated with suicidal ideation and an increased risk of suicide.³⁴ Prescription opioids and benzodiazepines are the top 2 causes of overdose-related deaths (benzodiazepines are involved in approximately 31% of fatal overdoses³⁵), and from 2002 to 2015 there was a 4.3-fold increase in deaths from benzodiazepine overdose in the United States.³⁶ CDC guidelines recommend against co-prescribing opioids and benzodiazepines because of the risk of death by respiratory depression.³⁷ As of August 2016, the FDA required black-box warnings for opioids and benzodiazepines regarding the risk of respiratory depression and death when these agents are used in combination, noting that “If these medicines are prescribed together, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect.”^38,39

A sensible approach to prescribing

Given the risks posed by benzodiazepines, what would constitute a sensible approach to their use? Clearly, there are some patients for whom benzodiazepine use should be minimized or avoided (Table 3). In a patient who is deemed a good candidate for benzodiazepines, a long-acting agent may be preferable because of the increased risk of dependence associated with short-acting compounds. Start with a low dose, and use the lowest dose that adequately treats the patient’s symptoms.⁴⁰ Using scheduled rather than “as-needed” dosing may help reduce behavioral escape patterns that reinforce anxiety and dependence in the long term.

Before starting a patient on a benzodiazepine, discuss with him (her) the risks of use and an exit plan to discontinue the medication. For example, a benzodiazepine may be prescribed at the same time as a selective serotonin reuptake inhibitor (SSRI), with the goal of weaning off the benzodiazepine once the SSRI has achieved efficacy.⁶ Inform the patient that prescribing or treatment may be terminated if it is discovered that the patient is abusing or diverting the medication (regularly reviewing the state prescription monitoring program database can help determine if this has occurred). Strongly consider using non-benzodiazepine treatments for anxiety with (or eventually in place of) benzodiazepines (Table 4⁴¹).

Reducing or stopping benzodiazepines can be challenging.⁴² Patients often are reluctant to stop such medications, and abrupt cessation can cause severe withdrawal. Benzodiazepine withdrawal symptoms can be severe or even fatal. Therefore, a safe and collaborative approach to reducing or stopping benzodiazepines is necessary. A starting point might be to review the risks associated with benzodiazepine use with the patient and ask about the frequency of use. Discuss with the patient a slow taper, perhaps reducing the dose by 10% to 25% increments weekly to biweekly.^43,44 Less motivated patients may require a slower taper, more time, or repeated discussions. When starting a dose reduction, notify the patient that some rebound anxiety or insomnia are to be expected. With any progress the patient makes toward reducing his usage, congratulate him on such progress.

Bottom Line

Benzodiazepines can be useful tools, but they also carry substantial risks. A sensible approach to prescribing these medications can help mitigate some of these risks, as can using non-benzodiazepine treatments for anxiety.

Related Resources

Johns Hopkins Psychiatry Guide. Benzodiazepines. https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_Psychiatry_Guide/787140/all/Benzodiazepines.
Bostwick JR, Casher MI, Yasugi S. Benzodiazepines: a versatile clinical tool. Current Psychiatry. 2012;11(4):54-56,59-63,A.
Casher MI. Benzodiazepines and stimulants for patients with substance use disorders. Current Psychiatry. 2011;10(5):58-62, 64-67.

Drug Brand Names

Alprazolam • Xanax
Buspirone • BuSpar
Chlordiazepoxide • Librium
Clonazepam • Klonopin
Diazepam • Valium
Diphenhydramine • Benadryl
Gabapentin • Neurontin
Hydroxyzine • Vistaril
Lamotrigine • Lamictal
Lorazepam • Ativan
Mirtazapine • Remeron
Oxazepam • Serax
Pregabalin • Lyrica
Propranolol • Inderal
Temazepam • Restoril
Topiramate • Topamax
Triazolam • Halcion

Benzodiazepines: Sensible prescribing in light of the risks

References

A sensible approach to prescribing

Bottom Line

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