Concerns About Long-Term Benzodiazepine Treatment and the State of the Evidence: Reply to Sigler et al

Edward Silberman, MD; Antonio E. Nardi, MD PhD; Vladan Starcevic, MD PhD; Richard Balon, MD; Fiametta Cosci, MD; Giovanni A. Fava, MD; Carl Salzman, MD; Richard Shader, MD; Nicoletta Sonino, MD

J Clin Psychiatry 2024;85(2):24lr15306a

See letter by Sigler et al and commentary by Silberman et al

To the Editor: We thank Sigler et al¹for their interest in the questions about benzodiazepines raised in our recent commentary.²The issues flagged in their letter are a sample of the variety of concerns raised about these medications and the differing degrees to which the extant evidence base addresses them.

While some earlier reports suggested a link between benzodiazepine use and dementia, others found none; more recent studies, with arguably more definitive methodology, failed to confirm the relationship. Dubovsky and Marshall³have summarized this literature. While benzodiazepines have not been proven to cause dementia, future research may modify the present picture.

The evidence base that we described as finding long-term benzodiazepine use to be “stable and unproblematic” consists of at least 7 naturalistic follow up studies,^4–102 double-blind controlled studies,^11,121 small survey study,¹³and more recently, a large national register based study.¹⁴While not as extensive as the topic deserves, these reports are unanimous in finding dose stability and consistent benefits for patients taking benzodiazepines for up to 3 years; we have found no systematic research contradicting these findings, and none has been brought to our attention. Sigler et al correctly point out that prescribing guidelines typically caution against long term use of benzodiazepines, but such recommendations ignore, rather than reflect the extant evidence.

Finally, there are patients who have had severe and/or persistent adverse effects associated with both taking and withdrawing from long-term benzodiazepines. Such outcomes have been the subject of essentially no systematic research,¹⁵and they appear in adverse effect surveys and anecdotally in the withdrawal literature.^16,17We therefore have no basis for understanding the risk factors and mechanisms for such adverse experiences, or the reasons why the efficacy and tolerability literature contains little sign of them.

The question should not be which of these pictures are correct, but which is a likely outcome for whom, under what conditions of treatment and withdrawal. For example, while the withdrawal literature suggests that up to one-third of patients are unable to complete a taper,¹⁷Nardi and others have successfully tapered patients who are personally motivated to come off their medication, using a slow taper, without major difficulty.^18,19There is substantial support for long-term benzodiazepines as safe, effective antianxiety medications for patients with diagnosed anxiety disorders, as well as reason for concern that they may be harmful to other, as yet poorly defined patient groups. Understanding the past treatment and withdrawal histories of people with long-term adverse outcomes to benzodiazepine use would be an important focus of future research.

Article Information

Published Online: May 27, 2024. https://doi.org/10.4088/JCP.24lr15306a
© 2024 Physicians Postgraduate Press, Inc.
J Clin Psychiatry 2024;85(2):24lr15306a
To Cite: Silberman E, Nardi AE, Starcevic V, et al. Concerns about long-term benzodiazepine treatment and the state of the evidence: reply to Sigler et al. J Clin Psychiatry. 2024;85(2):24lr15306a.
Author Affiliations: Tufts University School of Medicine, Boston, Massachusetts (Silberman, Shader); Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (Nardi); University of Sydney, Camperdown, Australia (Starcevic); Wayne State University School of Medicine, Detroit, Michigan (Balon); University of Florence, Florence, Italy (Cosci); State University of New York, Buffalo, New York (Fava); Harvard Medical School, Boston, Massachusetts (Salzman); University of Padova, Padua, Italy (Sonino).
Corresponding Author: Edward Silberman, MD, Tufts University School of Medicine, 800 Washington St, #1007, Boston, MA 02111 ([email protected]).
Relevant Financial Relationships: The authors had no conflicts of interest in preparing the commentary discussed in this letter.
Funding/Support: The authors received no funding for the preparation of this commentary discussed in this letter.
Additional Information: The authors are members of the International Task Force on Benzodiazepines.

Author Affiliations

Tufts University School of Medicine, Boston, Massachusetts
Corresponding Author: Edward Silberman, MD, Tufts University School of Medicine, 800 Washington St, #1007, Boston, MA 02111 ([email protected]).
Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
University of Sydney, Camperdown, Australia
Wayne State University School of Medicine, Detroit, Michigan
University of Florence, Florence, Italy
State University of New York, Buffalo, New York
Harvard Medical School, Boston, Massachusetts
Tufts University School of Medicine, Boston, Massachusetts
University of Padova, Padua, Italy

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