See reply by Silberman et al and commentary by Silberman et al
To the Editor: Benzodiazepine exposure has resulted in considerable long-term harms to some patients1 and benefits to others. The problem with benzodiazepine prescribing is that we have no way of knowing to which group a prospective patient belongs.
“Resolving the Paradox of Long Term Benzodiazepine Treatment: Toward Evidence-Based Practice Guidelines” by Silberman et al2 published recently in JCP recommends greater guidance in benzodiazepine prescribing, which we wholeheartedly endorse. However, we must first resolve the paradox of harm/benefit among seemingly comparable benzodiazepine patient groups and the implications of long-term use.
This paradox manifests itself in conflicting literature about benzodiazepines. For example, the authors state that there is no confirmed relationship between benzodiazepine use and dementia, citing a single study. However, 2 independent 2018 systematic reviews have previously suggested the opposite.3,4 The authors state that benzodiazepines are unproblematic and do not lose their therapeutic effect, but this was challenged by the US Food and Drug Administration (FDA) medication guide for each of the 4 most commonly prescribed benzodiazepines. The FDA reviewed the existing evidence for efficacy and duration of use, concluding that these medications have not been demonstrated to be effective for long-term use beyond 4 months (and only 9 weeks for clonazepam). In addition, these FDA guides state, “The continued use of benzodiazepines … may lead to clinically significant physical dependence.”5
We agree with the authors that patients should be thoroughly informed before consenting to initiate or discontinue benzodiazepines, so they can make an evidence-based decision for themselves.6 We would like to thank the authors for acknowledging the recent reviews that have shown that both benzodiazepines and antidepressants can have persistent and problematic withdrawal symptoms and life impacts when used long term.7–9
The potential harms of benzodiazepine use are real and substantial, even if they impact only a subpopulation of benzodiazepine users. It is urgent that we study why these long-term symptoms occur and in whom, with the goal of identifying potential risk factors. The ability of clinicians to risk-stratify prospective patients would greatly reduce benzodiazepine injury while at the same time affording confidence to clinicians in making prescribing choices.
Ritvo AD, Foster DE, Huff C, et al. Long-term consequences of benzodiazepine-induced neurological dysfunction: a survey. PLoS One. 2023;18(6):e0285584. PubMedCrossRef
Silberman E, Nardi AE, Starcevic V, et al. Resolving the paradox of long-term benzodiazepine treatment: toward evidence-based practice guidelines. J Clin Psychiatry. 2023;84(6):23com14959. PubMedCrossRef
Lucchetta RC, da Mata BPM, de Carvalho Mastroianni P. Association between development of dementia and use of benzodiazepines: a systematic review and meta-analysis. Pharmacotherapy. 2018;38(10):1010–1020. PubMedCrossRef
Penninkilampi R, Eslick GD. A systematic review and meta-analysis of the risk of dementia associated with benzodiazepine use, after controlling for protopathic bias. CNS Drugs. 2018;32(6):485–497. PubMedCrossRef
Nielsen M, Hansen EH, Gøtzsche PC. What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors. Addiction. 2012;107(5):900–908. PubMedCrossRef
Cosci F, Chouinard G. Acute and persistent withdrawal syndromes following discontinuation of psychotropic medications. Psychother Psychosom. 2020;89(5):283–306. PubMedCrossRef
Jauhar S, Hayes J, Goodwin GM, et al. Antidepressants, withdrawal, and addiction; where are we now? J Psychopharmacol. 2019;33(6):655–659. PubMedCrossRef