Experiences with benzodiazepine use, tapering, and discontinuation: an Internet survey

Finlayson, A. J. Reid; Macoubrie, Jane; Huff, Christy; Foster, D. E.; Martin, Peter R.

doi:10.1177/20451253221082386

Cited by 17 publications

(31 citation statements)

References 28 publications

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“…Therefore, increases in anxiety during and after BZD withdrawal may lead to unsuccessful discontinuation or relapse. As anxiety is one of the most common symptoms occurring during BZD withdrawal [ 36 ], it is paramount to determine whether flumazenil produces an anxiogenic response, as worsening of anxiety may result in poorer outcomes.…”

Section: Discussionmentioning

confidence: 99%

Is the Precipitation of Anxiety Symptoms Associated with Bolus Doses of Flumazenil a Barrier to Its Use at Low Continuous Doses in Benzodiazepine Withdrawal?

Gallo

MacDonald

Bennett

et al. 2022

JCM

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Introduction: Benzodiazepines (BZDs) are used in the management of anxiety and sleep disorders; however, chronic use is associated with tolerance and dependence. During withdrawal, symptoms of anxiety are often severe and problematic for patients and may lead to relapse or maintenance on low doses of BZDs. Low, continuous doses of flumazenil reduce BZD withdrawal symptoms in several studies; however, bolus doses are known to induce anxiety and precipitate panic. Accordingly, this study aimed to determine whether continuous low-dose flumazenil is anxiogenic like bolus doses. Method: In a randomised control cross over design, participants received a continuous low-dose flumazenil infusion for eight days at an approximate rate of 4 mg/24 h or placebo before crossing over to the alternate study arm. Participants were able to request diazepam as needed. The primary outcome was the change in state anxiety levels. Trait anxiety was also recorded at baseline and one month after the flumazenil/placebo infusion period. Results: BZD use was significantly reduced in both groups. There were no significant differences between state anxiety and the 95% confidence interval showed no evidence of a clinically significant anxiogenic effect from low-dose flumazenil. Trait anxiety was significantly reduced one month after the infusion period. Conclusion: There is no evidence that continuous low-dose flumazenil infusion significantly increases state anxiety levels to a clinically significant level. Interestingly, flumazenil may decrease state anxiety during BZD withdrawal, unlike bolus doses of flumazenil. Flumazenil may have an anxiolytic effect on trait anxiety, which was evident one month after treatment.

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Section: Discussionmentioning

confidence: 99%

Is the Precipitation of Anxiety Symptoms Associated with Bolus Doses of Flumazenil a Barrier to Its Use at Low Continuous Doses in Benzodiazepine Withdrawal?

Gallo

MacDonald

Bennett

et al. 2022

JCM

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show abstract

“…In 2020, FDA issued a requirement to update the Boxed Warning on BDZs, indicating that following chronic use of BDZs over several days or weeks, abrupt cessation or dose reduction of BDZs can cause severe withdrawal symptoms, including seizures ( 1 ). Indeed, studies indicate that withdrawal symptoms can continue for months, even years ( 55 ). In a recent Internet study, 60–85% of individuals reported having moderate to very severe symptoms in different life domains while tapering off BDZs, with 54% of them reporting suicidal thoughts ( 55 ).…”

Section: Benzodiazepine Abuse and Misusementioning

confidence: 99%

“…Indeed, studies indicate that withdrawal symptoms can continue for months, even years ( 55 ). In a recent Internet study, 60–85% of individuals reported having moderate to very severe symptoms in different life domains while tapering off BDZs, with 54% of them reporting suicidal thoughts ( 55 ). The challenges involved in discontinuing BDZs were present even when tapering was done in a clinical setting where the withdrawal symptoms were closely managed ( 56 , 57 ).…”

Section: Benzodiazepine Abuse and Misusementioning

confidence: 99%

GABAA receptor subtypes and benzodiazepine use, misuse, and abuse

Engin

2023

Front. Psychiatry

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Benzodiazepines have been in use for over half a century. While they remain highly prescribed, their unfavorable side-effect profile and abuse liability motivated a search for alternatives. Most of these efforts focused on the development of benzodiazepine-like drugs that are selective for specific GABAA receptor subtypes. While there is ample evidence that subtype-selective GABAA receptor ligands have great potential for providing symptom relief without typical benzodiazepine side-effects, it is less clear whether subtype-selective targeting strategies can also reduce misuse and abuse potential. This review focuses on the three benzodiazepine properties that are relevant to the DSM-5-TR criteria for Sedative, Hypnotic, or Anxiolytic Use Disorder, namely, reinforcing properties of benzodiazepines, maladaptive behaviors related to benzodiazepine use, and benzodiazepine tolerance and dependence. We review existing evidence regarding the involvement of different GABAA receptor subtypes in each of these areas. The reviewed studies suggest that α1-containing GABAA receptors play an integral role in benzodiazepine-induced plasticity in reward-related brain areas and might be involved in the development of tolerance and dependence to benzodiazepines. However, a systematic comparison of the contributions of all benzodiazepine-sensitive GABAA receptors to these processes, a mechanistic understanding of how the positive modulation of each receptor subtype might contribute to the brain mechanisms underlying each of these processes, and a definitive answer to the question of whether specific chronic modulation of any given subtype would result in some or all of the benzodiazepine effects are currently lacking from the literature. Moreover, how non-selective benzodiazepines might lead to the maladaptive behaviors listed in DSM and how different GABAA receptor subtypes might be involved in the development of these behaviors remains unexplored. Considering the increasing burden of benzodiazepine abuse, the common practice of benzodiazepine misuse that leads to severe dependence, and the current efforts to generate side-effect free benzodiazepine alternatives, there is an urgent need for systematic, mechanistic research that provides a better understanding of the brain mechanisms of benzodiazepine misuse and abuse, including the involvement of specific GABAA receptor subtypes in these processes, to establish an informed foundation for preclinical and clinical efforts.

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“…Due to their rapid effectiveness and low toxicity, BDZs often represent the first treatment administered by general practitioners and other specialists, also outside of psychiatric setting [ 6 , 7 ]. However, in the last decades, physicians’ enthusiasm has been curbed by emerging concerns about abuse, dependence, higher risk of falls, and possible cognitive disturbances [ 6 , 8 , 9 , 10 , 11 ]. Both chronic and inappropriate benzodiazepine (BDZ) intake represent, indeed, an important health and social concern worldwide [ 7 ], leading to an increased risk of oversedation, cognitive and psychomotor impairment, and physical injuries [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Add-On Treatment with Passiflora incarnata L., herba, during Benzodiazepine Tapering in Patients with Depression and Anxiety: A Real-World Study

et al. 2023

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Chronic and inappropriate benzodiazepine intake represents an important health and social concern worldwide. The aim of our study was to investigate the effectiveness of P. incarnata L., herba, in reducing benzodiazepine misuse in a real-world population of depressed and anxious patients in a long-term treatment with benzodiazepines. We conducted a retrospective naturalistic study on 186 patients undergoing benzodiazepine downtitration, 93 with the addition of a dry extract of P. incarnata L., herba (Group A), and 93 without any add-on treatment (Group B). Regarding the benzodiazepine dosage variation in the two groups, a repeated measure ANOVA showed a significant effect of time (p < 0.001), group (p = 0.018), and time x group interaction (p = 0.011). We found a significantly higher rate, i.e., of 50%, reduction in Group A vs. Group B at 1 month (p < 0.001) and at 3 months (p < 0.001) and complete benzodiazepine discontinuation at 1 month (p = 0.002) and at 3 months (p = 0.016). Our findings suggest the role of P. incarnata as an effective add-on treatment during benzodiazepine tapering. These findings highlight the need for further studies to better investigate the promising properties of P. incarnata in the management of such a relevant clinical and social issue.

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Experiences with benzodiazepine use, tapering, and discontinuation: an Internet survey

Cited by 17 publications

References 28 publications

Is the Precipitation of Anxiety Symptoms Associated with Bolus Doses of Flumazenil a Barrier to Its Use at Low Continuous Doses in Benzodiazepine Withdrawal?

Is the Precipitation of Anxiety Symptoms Associated with Bolus Doses of Flumazenil a Barrier to Its Use at Low Continuous Doses in Benzodiazepine Withdrawal?

GABAA receptor subtypes and benzodiazepine use, misuse, and abuse

Add-On Treatment with Passiflora incarnata L., herba, during Benzodiazepine Tapering in Patients with Depression and Anxiety: A Real-World Study

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