Evidence-Based Reviews

Benzodiazepines: Sensible prescribing in light of the risks

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Understand the risks and consider alternative treatments, especially in high-risk patients


 

References

As a group, anxiety disorders are the most common mental illness in the Unites States, affecting 40 million adults. There is a nearly 30% lifetime prevalence of anxiety disorders in the general population.1 DSM-5 anxiety disorders include generalized anxiety disorder, social anxiety disorder (social phobia), panic disorder, specific phobia, and separation anxiety disorder. Although DSM-IV-TR also classified obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) as anxiety disorders, these diagnoses were reclassified in DSM-5. Anxiety also is a frequent symptom of many other psychiatric disorders, especially major depressive disorder.

For many years, benzodiazepines have been a mainstay in the treatment of anxiety.2 They work by enhancing the effect of γ-aminobutyric acid (GABA) by positive allosteric modulation of the GABAA receptor, which decreases neuronal excitability and produces a calming effect. Most benzodiazepines have a rapid onset of action, but their duration of action varies (Table 13). Benzodiazepines also are used to treat several nonpsychiatric conditions (Table 2).


Although benzodiazepines have many potential uses, they also carry risks that prescribers should recognize. This article reviews some of the risks of benzodiazepine use, identifies patients with higher risks of adverse effects, and presents a practical approach to prescribing these medications.

A wide range of risks

Abuse and addiction. Perhaps the most commonly recognized risk associated with benzodiazepine use is the potential for abuse and addiction.4 Prolonged benzodiazepine use typically results in physiologic tolerance, requiring higher dosing to achieve the same initial effect.5 American Psychiatric Association practice guidelines recognize the potential for benzodiazepine use to result in symptoms of dependence, including cravings and withdrawal, stating that “with ongoing use, all benzodiazepines will produce physiological dependence in most patients.”6 High-potency, short-acting compounds such as alprazolam have a higher risk for dependence, toxicity, and abuse.7 However, long-acting benzodiazepines (such as clonazepam) also can be habit-forming.8 Because of these properties, it is generally advisable to avoid prescribing benzo­diazepines (and short-acting compounds in particular) when treating patients with current or past substance use disorders, except when treating withdrawal.9

Limited efficacy for other disorders. Although benzodiazepines can help reduce anxiety in patients with anxiety disorders, they have shown less promise in treating other disorders in which anxiety is a common symptom. Treating PTSD with benzodiazepines does not appear to offer any advantage over placebo, and may even result in increased symptoms over time.10,11 There is limited evidence supporting the use of benzodiazepines to treat OCD.12,13 Patients with borderline personality disorder who are treated with benzodiazepines may experience an increase in behavioral dysregulation.14

Physical ailments. Benzodiazepines can affect comorbid physical ailments. One study found that long-term benzodiazepine use among patients with comorbid pain disorders was correlated with high utilization of medical services and high disability levels.15 Benzodiazepine use also has been associated with an increased risk of exacerbating respiratory conditions, such as chronic obstructive pulmonary disease,16 and increased risk of pneumonia.17,18

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