Assessing Pharmacist Awareness of Benzodiazepines’ Long-Term Withdrawal Effects

1. Introduction

Benzodiazepines are a class of medication used to treat anxiety, seizures, muscle spasms, and insomnia. They exert their effects by increasing the frequency of GABA channel opening in the brain. Their use is associated with risks such as cognitive impairment, overdose when used concurrently with other central nervous system depressants, and physiological dependence. They can have both acute and long-term adverse effects, the latter of which are not well understood and can occur after full discontinuation of the drug. The lack of research into benzodiazepines’ long-term side effects can lead to misinformation in prescribing and treatment settings [9]. Because of this, individuals that report continuing symptoms may be met with skepticism in clinical settings.

BIND (benzodiazepine induced neurological dysfunction) is a newly proposed term used to describe the adverse effects of benzodiazepine usage, particularly their long-term withdrawal symptoms. BIND is not yet associated with established diagnostic criteria and should be interpreted as an emerging term. Additionally, the 2023 survey that proposed the term received a 2026 editorial note that identified that the study’s findings were not assessed or questioned as part of the peer-review process [11]. However, assigning a clinical term to these symptoms may aid healthcare practitioners in devising treatment regimens and having productive discussions with their patients.

BIND may present as de novo symptoms that start up to a year after benzodiazepines are discontinued and can last for additional months/years [9]. Examples of long-term side effects post benzodiazepine usage may include symptoms like low energy, myalgia, extreme anxiety, insomnia, and digestive issues. Quality of life is significantly affected (suicidal ideation and negative impacts on work, family, and relationships). Treatment for persistent symptoms would differ from guideline-directed therapy for acute symptoms and should be further investigated.

Evidence regarding withdrawal and deprescribing is evolving. Withdrawal varies significantly between patients, with some experiencing neurologic symptoms for weeks, months, or longer. However, the prevalence and cause of these symptoms in certain individuals is unclear [10]. As supported by contemporary guidelines [8], continued discussion and adopting a patient-centered approach to tapering and deprescribing is crucial [1,4]. The Ashton Manual, a guide for non-health professionals, is a resource that describes the function of benzodiazepines and how to taper off of them after long-term use [2].

The FDA boxed warning for benzodiazepines has been updated [12] to include more specific precautions about the medication. It emphasizes the probability of abuse despite prescribing the lowest effective dose for less than 4 weeks [3], an increased likelihood of misuse and harm when used with opioids and alcohol, and severe withdrawal symptoms without gradual tapering. Recent multidisciplinary guidance draws attention to the dangers of long-term benzodiazepine use and the importance of individual risk-benefit assessment, shared decision making, and avoidance of abrupt discontinuation [8].

Pharmacists have a major role in ensuring medication safety, counseling patients, identifying tapering strategies, and collaborating with providers on preventing inappropriate medication use [5,6]. They are also crucial in reducing harmful prescribing patterns and deprescribing benzodiazepines in older adults [5,6], particularly as this is a population where long-term benzodiazepine use persists [7]. However, data on pharmacist awareness of persistent symptoms following benzodiazepine discontinuation or their confidence counseling patients and prescribers is minimal. The objective of this study was to assess persistent benzodiazepine withdrawal symptoms following discontinuation and whether brief educational exposure would alter pharmacist perceptions and confidence.

Note that patient reported information is not intended to establish prevalence of BIND or establish it as a diagnosis and was primarily used to develop the pharmacist web-survey.

2. Methods

Study Design and Overview: This exploratory study was a two-stage survey conducted from September 2024 to October 2025. Patients with self-identified BIND provided formative data that informed the development of a subsequent survey to Colorado pharmacists. The pharmacist survey assessed baseline awareness of BIND before and after educational exposure without the utilization of a control group.

Stage One: Individuals from the Benzodiazepine Action Work Group were recruited through open invitation. Respondents were de-identified and were invited to provide formative input through a Qualtrics survey on their experiences with benzodiazepine use, discontinuation, withdrawal symptoms, and interactions with healthcare providers.

Eligible participants were those who had discontinued benzodiazepines and were experiencing symptoms consistent with long-term withdrawal. Individuals who were currently taking benzodiazepines or were experiencing acute symptoms from recent discontinuation of benzodiazepines were not eligible for this study. Participants answered a set of qualifying questions upon initiating the survey and were exited out if they did not fit the inclusion criteria.

Results were analyzed descriptively to identify themes (i.e. gaps in care, recurring symptoms) that informed the development of the survey to pharmacists in Stage Two. As survey data was self-reported, not independently verified, and derived from an advocacy group, findings are not intended to establish causality or incidence of BIND and merely serve as perceptions of the respondent.

Stage Two: Licensed Colorado pharmacists were recruited through convenience sampling (distribution via professional networks and email outreach to the Colorado Pharmacists Society, Children’s Hospital Colorado, UCHealth, Swedish Medical Center, and community pharmacy networks). If pharmacists practiced outside of Colorado, they were not eligible for the study and were exited out of the survey. Duplicate responses were prevented through Qualtrics settings. As distribution denominators are unknown, an overall response rate cannot be calculated.

The pharmacist survey was administered via Qualtrics (Qualtrics, Provo, UT) and consisted of:

• Identifying demographic characteristics and practice settings of the respondent
• Assessing baseline knowledge of BIND and rating the likelihood of long-term benzodiazepine withdrawal as an explanation for a set of presented symptoms using a Likert-type scale (1-5)
• Exposing respondents to brief educational content, which included a definition of BIND, details on long-term withdrawal, and information from individuals from the formative survey in Stage One.
• Follow up questions on the likelihood of the pharmacist recognizing persistent symptoms, knowledge of benzodiazepine tapering, and confidence in educating providers and patients on BIND. The survey concluded with an updated Likert-type scale assessing changes in perceptions.

Outcomes: The primary outcome was the change in the Likert-Type scale rating of pharmacists recognizing benzodiazepine-related withdrawal symptoms and attributing symptoms to the medication before and after education. Secondary outcomes included baseline awareness of BIND, awareness of the updated boxed warning, ability to recognize withdrawal symptoms in practice, self-reported recognition of patients with related symptoms in practice, knowledge of tapering strategies, and confidence in educating patients and providers.

Statistical Analysis: Categorical variables were analyzed through percentages and frequencies, with ordinal data summarized through averages, medians, and distributional frequencies via Excel and Qualtrics. The association between prior knowledge of BIND and self-reported recognition of symptoms in practice was assessed via the Fisher Exact Test. The Wilcoxon Signed Ranks Test was used to compare paired Likert-scale responses before and after educational exposure. Statistical significance was assessed at an alpha level of 0.05.

Ethical Considerations: Individual participation in the study was both voluntary and anonymous and posed minimal risk to respondents. The study was reviewed and approved by the University of Colorado Institutional Review Board (COMIRB Protocol #24-1553).

3. Results

Survey One (Patient Reported Experiences):

32 individuals initiated the survey, and 16 met the inclusion criteria. 13 of the 16 respondents that qualified completed the survey in its entirety. Reported item-level denominators ranged from 13 to 16.

7 respondents of 14 (50%) reported taking benzodiazepines for >5 years, with 9 of 14 (64.3%) being off them for ~1-5 years. Among 13 respondents, all report continuing to experience withdrawal symptoms with either increased or decreased intensity. Respondents attributed these symptoms to benzodiazepine usage based on their relative association with medication discontinuation (with 13 of 14 (92.8%) reporting symptoms beginning immediately after benzodiazepine cessation).

6 of 13 respondents took benzodiazepines for anxiety disorder (46%), and the rest were prescribed the medication for muscle spasms and insomnia. Out of a provided set of symptoms (anxiety, sleep disturbances, muscle weakness, depression, suicidal ideation, and muscle spasms), the most commonly selected were sleep disturbances (12/14, 85.7%), anxiety (11/14, 78.6%), depression (9/14, 64.3%), and muscle spasms (7/14, 50.0%). Participants were permitted to self-report withdrawal symptoms that were not included in an “other” category, and these symptoms were broadly categorized into six groups: balance and motor control issues, hypersensitivity, generalized pain, gastric issues and “benzo belly”, cognition problems, and irritability/hyperactivity. Symptoms that were reported by multiple respondents but did not fall under these categories included neuropathy, joint instability, tinnitus, changes in vision, and blood pressure.

Persistent benzodiazepine withdrawal symptoms were stated to have significant negative impacts, with most citing inability to work, loss of relationships, loss of mobility, and loss of independence as the primary detriments to their quality of life. Coping mechanisms included meditation, yoga, online support, and sensory deprivation.

13 of 13 respondents reported no prescriber elaboration on benzodiazepines’ negative side effects or risk of dependence. 9 out of 14 respondents (64.3%) reported an abrupt discontinuation rather than undergoing a taper. Participants reported being told by providers that they would be able to stay on the medication for an extended period of time, could take additional pills as needed, and would not experience any side effects.

5 of 6 participants who asked a pharmacist about benzodiazepines stated that they did not question the prescription or counsel them on the medication. With strict regulations on controlled substances, individuals reported they were called drug seekers. However, one individual reported that their pharmacist was the only provider that counseled them on the intended short-term use of benzodiazepines.

Various barriers to effective care were reported as a lack of time to interact with patients, insufficient FDA studies, and preconceived notions towards patients on benzodiazepines. Advice to pharmacists included prioritizing the patient, listening to lived experiences, remaining curious, and initiating conversations. Due to the variety of adverse effects that can result from benzodiazepines, patient-reported symptoms may not correlate with those that are documented in literature. Prescription length and signs of cognitive impairment and iatrogenic harm should also be evaluated.

These findings informed the development of the survey administered to pharmacists, which focused on improving communication, management, and recognizing symptoms. As findings were derived from a benzodiazepine advocacy group and self-reported, they should not be used to establish causality or proof of diagnosis.

Stage Two: Pharmacist Survey

100 pharmacists initiated the survey, and 62 met the inclusion criteria. 52 of the 62 respondents that qualified completed the survey in its entirety and were included in the primary analysis. For certain questions, analyses were conducted using all available responses, resulting in varying sample sizes due to nonresponse.

Among the 62 pharmacists that answered questions on demographic background, 32 (51.6%) practiced in an inpatient hospital, 18 (29%) in a hospital/health-system outpatient setting, 9 (14.5%) in a chain community pharmacy, and 7 (11.3%) in an independent community pharmacy (respondents could select more than one area of practice). 10 of 62 (16.1%) pharmacists were a part of a Health Professional Shortage Area (HPSA). Respondents had an even distribution of practice experience among the provided categories (0-5 years, 6-10 years, 11-15 years, and 20+ years; a 16-19 years category was absent in error).

58 pharmacists completed questions that assessed baseline awareness of benzodiazepines and BIND. Pharmacists’ baseline awareness of BIND was limited, along with knowledge of the updated FDA boxed warning. 16 of 58 (28%) reported reading the benzodiazepine boxed warning, and 22 of 58 (38%) were familiar with BIND or its associated symptoms prior to taking the survey. 38 of 58 (65.5%) respondents believe they have encountered one or more patients experiencing BIND.

A Fisher’s exact test reported a statistically significant association between prior knowledge of BIND and recognition of the term in practice (Effect Size/Cramér’s V=0.343, P=0.011). 55 respondents entered rankings for the pre/post Likert-Type perception scores. Of these, 30 had non-zero differences and were accounted for in the Wilcoxon signed-rank analysis. Educational exposure resulted in a modest change in rankings (average change of 3.42 to 3.47), but his difference was not found to be statistically significant (Wilcoxon Signed Ranks Test, W = 208.5, p=0.6039; median rankings equaled 4 before and 4 after education).

The withdrawal symptoms selected to be likely attributable to benzodiazepines were cognition changes (57 of 62 respondents (91.9%)), irritability/hyperactivity (57 of 62 respondents (91.9%), balance and motor issues (49 of 62 respondents (79%)), high blood pressure (37 of 62 respondents (59.7%), and vision changes (33 of 62 respondents (53.2%)). Pain (30 of 62 respondents (48.4%)), hypersensitivity (29 of 62 respondents (46.8%)), and gastric issues or bloating (17 of 62 respondents (27.4%)), the three other broad categories of symptoms reported in survey one, were not as commonly selected. Other symptoms provided were neuropathy (20 of 62 respondents (32.3%), tinnitus (13 of 62 respondents (21%)), and joint instability (5 of 62 respondents (8.1%)).

After being exposed to brief education, 48 of 58 respondents (82.8%) stated they would advise patients to talk with their prescriber about their symptoms, 42 of 58 (72.4%) would suggest strategies to help with withdrawal, and 37 of 58 (63.8%) would suggest consulting a BIND or benzodiazepine-tapering specialist. Among 55 respondents, common strategies selected to help prevent BIND were to assess whether patients had an appropriate indication for long-term therapy (43 respondents, 78.2%), counsel on risks of long-term therapy (41 respondents, 74.5%), contact the prescriber to discuss long-term use (40 respondents, 72.7%), and discuss tapering options with the patient when appropriate (39 respondents, 70.9%). The most selected reason pharmacists would not take preventative measures for BIND was a lack of knowledge (20 respondents, 36.4%).

Though pharmacists agreed they have specialized knowledge in benzodiazepines, most were only modestly comfortable discussing benzodiazepine tapering strategies (40 of 55 respondents (73%) selecting a ranking of 3 or below on a 0-5 Likert Type Scale ranging from not comfortable to very comfortable).

4. Discussion

This exploratory study assessed 1) long-term symptoms of individuals with self-reported BIND and 2) evaluated pharmacist awareness of benzodiazepine-related withdrawal symptoms and confidence in their management before and after education. Findings suggest that pharmacist awareness of BIND is limited, and that brief education may not bring about a significant change in perception scores. However, there is a significant association between prior knowledge of benzodiazepine withdrawal and recognition of associated symptoms in practice. Confidence in educating providers and patients on tapering was modest.

As BIND is a non-standardized term, findings should be interpreted with caution. These findings do not indicate the incidence or clinical validity of BIND. Though persistent symptoms following benzodiazepine discontinuation have been documented in literature, the mechanism of this mode of withdrawal remains uncertain [10].

Direct testimonials from individuals with self-reported BIND shed light on common symptoms, potential management strategies, and gaps in treatment. Patients described providers having difficulty understanding their condition, which further highlights the need for education and patient-centered care. Respondents suggested that pharmacists could improve their practice by assessing the length of prescriptions and noting signs of cognitive impairment and iatrogenic harm. Due to the novelty of BIND as a term, providers solely relying on existing studies of benzodiazepine withdrawal may not capture the range of patient experience.

Pharmacists were able to recognize major symptoms associated with long-term withdrawal, but pain, hypersensitivity, and gastric issues, common symptoms reported by individuals with BIND, were not commonly recognized. This is notable, as the term “benzo belly” was a term that appeared frequently in survey one. Additionally, only around one quarter of respondents reported reading the updated benzodiazepine boxed warning, and less than 4 in 10 reported prior familiarity with BIND or its associated symptoms.

The educational intervention was brief and was insufficient to produce a significant change in perception scores. This may also indicate the need for a standardized course and a more thorough assessment of baseline knowledge, which is consistent with broader literature suggesting that sustained educational approaches are often necessary to produce notable changes in practice. Other explanations for non-significance include limited statistical power and the use of a non-validated instrument.

These findings indicate potential gaps in pharmacy education. Given the complicated nature of benzodiazepine discontinuation and withdrawal, pharmacists may benefit from additional training in tapering strategies, patient communication, and interprofessional collaboration. Pharmacists play a prime role in ensuring appropriate prescribing practices [5] and preventing medication misuse. More assurance in tapering and provider education may allow pharmacists to further contribute to benzodiazepine safety.

Limitations: This study has several limitations. The sample sizes were small, and recruitment through convenience sampling in Colorado limits generalizability. Survey responses were self-reported and consisted of retrospective data, which could have led to response and recall bias. The survey instrument was not formally validated.

The first, formative survey did not include variables like age, concurrent medications, or comorbid conditions. Recruitment was from an advocacy group and was prone to selection bias. Data was self-reported, and potential confounders like concomitant medications and comorbid conditions were not documented. This sample does not represent the broader population of patients who have taken benzodiazepines. For these reasons, these findings should not be used to establish causality or incidence of BIND and should remain secondary.

As recruitment for both surveys occurred through multiple professional networks, an overall invitation denominator and response rate are not available. Item-level nonresponse produced varying denominators, but participants were not permitted to submit a duplicate response after initiating the survey.

As the pre and post Likert-Type scales in the pharmacist survey did not involve a control group and the educational intervention was brief, causality may not be effectively derived from these findings. The post-exposure survey may have also been susceptible to priming. The Wilcoxon Signed Ranks Test was performed after the 55 pre/post Likert-Type rankings were paired at the respondent level.

Future Directions: Future trials should focus on increasing sample size and interviewing pharmacists and patients from different regions and backgrounds. A standardized educational intervention (i.e. courses, modules) with comparison groups should be implemented to better assess a change in perception and confidence. Furthermore, pharmacy education should emphasize benzodiazepine tapering and withdrawal symptom management to build confidence in counseling patients and providers. BIND is not an official term, and more research is needed to establish diagnostic criteria, management strategies, and to potentially compare adverse effects and median time to onset between benzodiazepines.

5. Conclusion

This exploratory study found variability in pharmacist awareness of long-term benzodiazepine withdrawal effects and potential gaps in knowledge of tapering strategies and provider/patient education. Prior knowledge of BIND was reported to be significantly associated with recognition of related presentations in practice. Brief educational exposure may not be sufficient to significantly alter awareness and perception scores. Larger studies with more representative samples, validated instruments, and standardized education modules are needed to further support the findings in this study.