We thank Prashant Tibrewal and colleagues for their Correspondence, in which they argue that benzodiazepines are an important medication for refractory anxiety disorders. We agree. We wrote our Seminar1Penninx BWJH Pine DS Holmes EA Reif A for a broad clinical readership, and we were particularly careful about treatment recommendations that would apply for general care. Although benzodiazepines might be an option in specialised settings, the risk of inappropriate over-medication potentially leading to long-term use is considerable in primary care, leading to substantial public health problems.We do not question the overall efficacy of benzodiazepines for reducing anxiety symptoms.1Penninx BWJH Pine DS Holmes EA Reif A Large-scale (network) meta-analyses2Slee A Nazareth I Bondaronek P Liu Y Cheng Z Freemantle N Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis., 3Breilmann J Girlanda F Guaiana G et al.Benzodiazepines versus placebo for panic disorder in adults. show that benzodiazepines reduce anxiety symptoms significantly more than placebo in, for example, patients with generalised anxiety disorder or panic disorder. The efficacy of benzodiazepines was similar to that of antidepressants, but the acceptability of benzodiazepines was comparatively poor.2Slee A Nazareth I Bondaronek P Liu Y Cheng Z Freemantle N Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis., 3Breilmann J Girlanda F Guaiana G et al.Benzodiazepines versus placebo for panic disorder in adults. Also, on benzodiazepine withdrawal, anxiety symptoms often recur, leading to long-term benzodiazepine use. In line with pertinent guidelines by the National Institute for Health and Care Excellence,4National Institute for Health and Care Excellence
Anxiety disorders. we therefore do not consider benzodiazepines to be a first-line treatment option due to poor acceptability, their potential for adverse interactions with alcohol and opioids, the potential for addiction and dependence in groups at high risk, and increased risk for falls and cognitive impairment. Our views also consider the announcement from the US Food and Drug Administration in September, 2020, concerning an update to the boxed warning on all benzodiazepines to explicitly “address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions”5US Food and Drug Administration
FDA requiring boxed warning updated to improve safe use of benzodiazepine drug class. among this class of medications. The new prescribing information advises clinicians to warn patients of the risks of benzodiazepines, assess patients' risk of abuse, misuse, and addiction, use caution when co-prescribing benzodiazepines with opioids, and consider alternate therapies first. These were all leading arguments for us to indicate that benzodiazepines should be given cautiously and only after failure of first-line treatments.

We agree with Tibrewal and colleagues that benzodiazepines can be useful treatments in specialised settings, in which more patients might suffer from refractory anxiety disorders. However, detailed psychopharmacological knowledge, high-frequency monitoring to avoid long-term use, and careful assessment of their risk–benefit ratio, including screening for risk factors, are prerequisites for prescription. For patients already prescribed a benzodiazepine, clinicians should regularly re-evaluate the use of benzodiazepines, aiming for the lowest effective dose for the shortest treatment duration possible, and gradually taper off benzodiazepines after adequate remission. Under these specialised conditions, benzodiazepines are clearly valuable in the hands of the expert.

We declare no competing interests.

References1.Penninx BWJH Pine DS Holmes EA Reif A

Anxiety disorders.

Lancet. 397: 914-9272.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. 393: 768-7773.Breilmann J Girlanda F Guaiana G et al.

Benzodiazepines versus placebo for panic disorder in adults.

Cochrane Database Syst Rev. 3CD0106774.National Institute for Health and Care Excellence

Anxiety disorders.

5.US Food and Drug Administration

FDA requiring boxed warning updated to improve safe use of benzodiazepine drug class.

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DOI: https://doi.org/10.1016/S0140-6736(21)00931-4

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© 2021 Elsevier Ltd. All rights reserved.

ScienceDirectAccess this article on ScienceDirect Linked ArticlesAnxiety disorders

Anxiety disorders form the most common group of mental disorders and generally start before or in early adulthood. Core features include excessive fear and anxiety or avoidance of perceived threats that are persistent and impairing. Anxiety disorders involve dysfunction in brain circuits that respond to danger. Risk for anxiety disorders is influenced by genetic factors, environmental factors, and their epigenetic relations. Anxiety disorders are often comorbid with one another and with other mental disorders, especially depression, as well as with somatic disorders.

Full-Text PDF Benzodiazepines for the long-term treatment of anxiety disorders?

In their Seminar, Brenda Penninx and colleagues1 have strongly cautioned against the long-term use of benzodiazepines for anxiety disorders, commenting that these drugs only act acutely, lead to relapse after discontinuation, and are associated with dependency. Penninx and colleagues propose that benzodiazepines should only be administered as a short-term adjunct and never as monotherapy. We believe that this conclusion is not evidence-based and risks biasing clinicians against an important medication for refractory anxiety disorders.

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