Assessing suicide risk in chronic pain management: a narrative review across drug classes.

INTRODUCTION: Chronic pain presents a multifaceted challenge in clinical practice, necessitating a nuanced understanding of pharmacological interventions to optimize treatment outcomes. This review provides an outline of various pharmacological agents commonly used in chronic pain management and highlights their safety considerations, particularly regarding suicide risk. AREAS COVERED: This review discusses the role of antidepressants, anticonvulsants, GABA receptor agonists, NMDA receptor antagonists, corticosteroids, cannabis and cannabinoids, bisphosphonates, calcitonin, and alpha-2 adrenergic receptor agonists in chronic pain management. It assesses their therapeutic benefits, potential for misuse, and psychiatric adverse effects, including the risk of suicide. Each pharmacological class is evaluated in terms of its efficacy, safety profile, and considerations for clinical practice. We searched peer-reviewed English literature on the topic using the MEDLINE database without time restrictions. EXPERT OPINION: While pharmacological interventions offer promise in alleviating chronic pain, healthcare providers must carefully weigh their benefits against potential risks, including the risk of exacerbating psychiatric symptoms and increasing suicide risk. Individualized treatment approaches, close monitoring, and multidisciplinary collaboration are essential for optimizing pain management strategies while mitigating adverse effects. Ongoing research efforts are crucial for advancing our understanding of these pharmacological interventions and refining pain management practices.

The relationship between clinical impairment and blood drug concentration: Comparison between the most prevalent traffic relevant drug groups.

AIM: The aim of the present study was to investigate the relationship between blood concentrations of four different drug classes; ethanol, benzodiazepines, amphetamines and tetrahydrocannabinol (THC) and driver impairment as assessed by a clinical test of impairment (CTI). METHODS: Data was retrieved from a national database on CTI assessments and accompanying blood drug concentrations from apprehended drivers. All drug concentrations in blood were quantified using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS), and compared to the results of the CTI which were categorized as either "not impaired", "mildly impaired", "moderately impaired", or "considerably impaired". RESULTS: A total number of 15 514 individual mono drug-cases collected over 9 years was included. 89 % were men and the median age was 34 years. In addition, 3 684 individual cases with similar age and gender distribution where no drugs were detected, were included as a reference group. For ethanol and benzodiazepines the percentage of clinically impaired cases increased markedly from lower to higher concentration windows, from 60 % to 97 % for ethanol and from 38 % to 76 % for benzodiazepines. The corresponding increase for amphetamines and THC was modest, from 43 % to 58 % for amphetamines and from 41 % to 55 % for THC. The correlation between drug concentration and degree of impairment was high for ethanol (Spearman´s rho=0.548, p<0.001) and relatively high for benzodiazepines (Spearman´s rho=0.377, p<0.001), but low for amphetamines (Spearman´s rho=0.078, p<0.001) and THC (Spearman´s rho=0.100, p<0.001). CONCLUSION: The percentage of impaired drivers increased with increasing blood drug concentration for all four drug classes, most pronounced for ethanol and benzodiazepines and much less for amphetamines and THC. The median blood drug concentration increased with increasing magnitude of impairment for ethanol and benzodiazepines, while this was much less pronounced for amphetamines and THC. The ranges of drug concentrations, however, were wide for all four drug classes in all impairment categories as assessed by individual clinical examination.

Factors associated with hypnotics polypharmacy in the Japanese population.

OBJECTIVE: Insomnia disorder is a global public health issue, commonly treated with hypnotics. However, long-term use of benzodiazepine derivatives (BZDs), especially polypharmacy with this kind of drug, carries risks for dependence and abuse. This study using large-scale medical insurance records investigated the causes of polypharmacy through the treatment of insomnia disorder. METHODS: A cross-sectional study analyzed anonymized medical record data from July 2014 to March 2018 provided by a nationwide Japanese health insurance association covering 405,952 individuals. Outpatients prescribed at least one sleep medication were included. Demographic data, pharmacological classification of the drugs, and comorbidities were assessed using hierarchical logistic regression analysis to explore their associations with polypharmacy. RESULTS: Of the 33,212 outpatients who were prescribed sleep medications, 32.5 % were prescribed multiple types. After adjusting for demographics and type of sleep medications as covariates, hypnotic polypharmacy was significantly associated with younger age, the presence of certain kinds of comorbidities, and using BZD anxiolytics before bedtime with the highest adjusted odds ratios (8.01-9.39) when referenced with BZD hypnotics. On the other hand, usage of orexin receptor antagonists, melatonin receptor agonists, and Z-drugs indicated lower odds ratios (0.74-0.87). CONCLUSIONS: Hypnotic polypharmacy is relatively common in the Japanese general population. With the introduction of non-pharmacological therapy in mind, assessing patients' comorbidities and avoiding the use of benzodiazepines, especially BZD anxiolytics, before bedtime would be recommended to prevent polypharmacy.

[Pharmaceutical Interventions in Benzodiazepine users during the COVID-19 Pandemic]. / Intervenciones farmacéuticas en usuarios de benzodiacepinas durante la pandemia COVID-19.

Introduction: Pharmaceutical Intervention aims to optimize and rationalize the use, effectiveness, and safety of dispensed medications resolving drug-related problems (DRPs) and negative medicine outcomes (NMOs). Objectives: To evaluate Pharmaceutical Interventions in Benzodiazepines users during the COVID-19 pandemic from a Community Pharmacy. Method: Prospective observational, descriptive, and cross-sectional study (AEMPS code: DAA-CLO-2020-01) of Pharmaceutical Interventions offered by the community pharmacy between August 2020 and February 2021. Results: A total of 306 Pharmaceutical Interventions were conducted involving 127 patients. Health education and personalized medication information were the most common Pharmaceutical Interventions after detecting a high level of unfamiliarity with the Benzodiazepines among patients. Pharmaceutical Interventions leading to medical referrals accounted for 37.8% of the total, triggered by the detection of DRPs and/or NMOs or after identifying the patient as candidate for deprescription. These referrals included patients with a very high level of depression according to the Euroqol 5D-3L test. Pharmaceutical Interventions resulting in Medication Review with Follow-up Service were performed in 3.1% of patients. The patient acceptance rate of Pharmaceutical Interventions reached 98.4%. Conclusions: The high acceptance rate of Pharmaceutical Interventions reinforces the value of Community Pharmacy in optimizing and rationalizing Benzodiazepines usage, while strengthening the pharmacist-patient relationship. The COVID-19 pandemic posed challenges to pharmacist-physician collaboration despite of the availability of telecommunication protocols among healthcare professionals.

Pharmacist-Led Deprescribing of Opioids and Benzodiazepines in Older Adults: Examining Implementation and Perceptions.

Background: This study examines the implementation and perceptions of a pharmacist consultant deprescribing program aimed at reducing the risk of falls in older adults using opioids and benzodiazepines. Methods: This qualitative study conducted interviews with healthcare providers. The interviews were conducted from August to December 2021 and analyzed using inductive coding techniques. Results: Five participants, predominantly female MDs or PA-Cs from rural clinics, were interviewed. The participants adopted a pharmacist-led deprescribing program due to their heightened awareness of the opioid crisis, dedication to patient safety, and a desire for opioid deprescribing education. Initially, concerns included patient resistance and provider-driven barriers. However, over time, patient attitudes shifted toward greater openness to the program. The providers emphasized several critical needs for the success of the program: guaranteed access to pharmacists, tailored patient education, resources specific to providers, and financial support, including telehealth options. These factors were deemed essential to overcoming initial barriers and ensuring effective implementation. Conclusion: Integrating pharmacists into primary care settings shows promise for deprescribing opioids and benzodiazepines in older adults. Future research should explore telehealth options for patient-pharmacist consultations and expand the application of these findings to other healthcare settings. The study highlights the importance of awareness, patient education, access to resources (pharmacists), and provider support in addressing deprescribing among older adults.

Risk Characterization in Patients Using Benzodiazepines While Providing Pharmaceutical Care Dispensing Service.

BACKGROUND: Tolerance and dependence stand out as the most relevant risks observed during benzodiazepine (BZD) treatments. OBJECTIVES: To evaluate the degree of dependence of patients on BZD treatments using the Tyrer test; to define a profile of patients at risk of developing BZD dependence; and to discuss the role of the pharmaceutical care offered by the community pharmacy during dispensing. METHODS: Prospective cross-sectional descriptive observational study (August 2020-February 2021) involving 127 patients using BZD. They voluntarily answered a questionnaire during the dispensing pharmaceutical care service. The study was evaluated and codified (code: DAA-CLO-2020-01) by the Spanish Agency for Drugs and Health Products (AEMPS), and statistical analysis was performed with SPSS 25.0. RESULTS: 19.05% of patients using BZD were suspected of suffering from BZD tolerance, and 77.88% of all patients were identified as being at a high risk of BZD dependence. The Tyrer test for dependence indicated a mean score of 5.59 out of 13 points. An 18-fold increased risk of developing dependence was detected in the case of coexistence of high anxiety or depression. CONCLUSIONS: The community pharmacy, through protocolized care practices and supported by tools such as the Tyrer test, can play a decisive role in the detection, prevention, and resolution of the risks associated with BZD treatments.

ANXIOLYTICS: Origins, drug discovery, and mechanisms.

Anxiety is a part of the human condition and has been managed by psychoactive substances for centuries. The current medical need and societal demand for anxiolytic medicines has not abated. The present overview provides a brief historical introduction to the discovery of modern age anxiolytics that include the benzodiazepines together with a discussion of the continuing medical need for new antianxiety medications. The paper also discusses the use and impact of behavioral pharmacology in the preclinical development of anxiolytics. The review then highlights the diversity of mechanisms for creating a new generation of anxioltyics through mechanisms beyond the potentiation of GABAA receptors and the blockade of monoamine uptake. A discussion then follows on the behavioral specificity of action of anxiolytics that includes the concept of creating an anxioselective drug, one that targets anxiety without producing untoward effects that include sedation and dependence. The use of anxiolytics in the treatment of other conditions such as substance use disorder is also briefly reviewed. Finally, a brief summary of the current status of anxiolytic drug development is provided. The review concludes with the idea that despite a host of anxiolytic drugs, the lack of efficacy in some patients and the side-effects and safety issues associated with some of these medications demands alternative medicines. Current preclinical and clinical research is ongoing with the goal of identifying such compounds.

Risk of falls or fall-related injuries associated with potentially inappropriate medication use among older adults with dementia.

BACKGROUND: Potentially inappropriate medications (PIMs) are prevalent in older adults with dementia and subsequent falls or fall-related injuries. The present study determined the risk of falls or fall-related injuries associated with PIM use in older adults with dementia. METHODS: The National Health Insurance Service-Elderly Cohort Database 2.0 (NHIS-ECDB 2.0) was used for this self-controlled case series (SCCS) study. This study included 1430 participants who went through exposure and non-exposure periods of PIM application among patients with dementia and experienced outcome events of falls or fall-related injuries between January 2016 and December 2019. The incidence of falls or fall-related injuries during the exposure and post-exposure periods was compared with that during the non-exposure period. Beers Criteria were used to define PIMs in patients with dementia. Negative binomial regression was conducted. The incidence rate ratio (IRR) was used to determine the risk of falls or fall-related injuries. RESULTS: During the exposure periods in which falls or fall-related injuries occurred, the mean number of PIMs among patients with dementia was 3.76 (SD = 2.99), and the most commonly used PIMs among patients with dementia were first-generation antihistamines (n = 283; 59.1%). Compared to the non-exposure period, the adjusted IRR during the exposure period was 1.57 (95% CI = 1.39-1.76). The risk of falls or fall-related injuries was increased when PIM use in patients with dementia was initiated (1-14 days: IRR = 2.76, 95% CI = 2.31-3.28; 15-28 days: IRR = 1.95, 95% CI = 1.48-2.56; ≥ 29 days: IRR = 1.17, 95% CI = 1.01-1.35). Especially, an increased risk of falls or fall-related injuries was associated with greater PIM use among patients with dementia. CONCLUSION: Among older adults with dementia, PIMs significantly increase the risk of falls and fall-related injuries. Therefore, strategies should be developed to manage PIM prescriptions in patients with dementia to prevent falls.

Retrospective comparison of the effects of remimazolam and dexmedetomidine on postoperative delirium in elderly patients undergoing orthopedic surgery of the lower extremities under spinal anesthesia.

PURPOSE: Remimazolam is often used for perioperative sedation due to its rapid onset and offset. However, the possible association between remimazolam and postoperative delirium (POD) remains undetermined. The present study evaluated whether remimazolam increased the incidence of POD compared with dexmedetomidine in elderly patients undergoing orthopedic surgery of the lower extremities. METHODS: This retrospective study included patients aged ≥ 65 years who had undergone orthopedic surgery of the lower extremities under spinal anesthesia from January 2020 to November 2022 and were sedated with continuous intravenous infusion of dexmedetomidine or remimazolam. The incidence of POD was assessed through a validated comprehensive review process of each patient's medical records. The effect of remimazolam on the occurrence of POD compared with dexmedetomidine was evaluated by propensity score weighted multivariable logistic models. RESULTS: A total of 447 patients were included in the final analysis. The crude incidence of POD within 3 days after surgery was 7.5% (17/226) in the dexmedetomidine group and 11.8% (26/221) in the remimazolam group, increasing to 9.7% (22/226) and 15.8% (35/221), respectively (p = 0.073), within 5 days. The multivariable models showed that, compared with dexmedetomidine, intraoperative sedation with remimazolam significantly increased the occurrence of POD within 3 days (odds ratio [OR] 2.21, 95% confidence interval [CI] 1.31 to 3.82, p = 0.003) and 5 days (OR 2.10, 95% CI 1.32 to 3.40, p = 0.002). CONCLUSION: Compared with dexmedetomidine, remimazolam infusion may be associated with a higher risk of POD in elderly patients undergoing orthopedic surgery of the lower extremities under spinal anesthesia.

Deaths involving novel benzodiazepines in Victoria, Australia from 2018-2022.

Novel benzodiazepine (NBz) detections in Victorian coronial cases started early in 2018 and have continued to increase in number and type up to December 2022. The eleven different NBz detections included etizolam (n=82), flualprazolam (n=43), clonazolam or 8-aminoclonazolam (n=30), bromazolam (n=15), clobromazolam (n=13), phenazepam (n=13), flubromazolam (n=12), flubromazepam (n=8), desalkylflurazepam (n=6), diclazepam (n=2), and estazolam (n=1). The pattern of detections varied over the 5-year period, with different compounds appearing over different time frames. The most recent NBz to appear were bromazolam, clobromazolam, flubromazepam and phenazepam; whereas etizolam had been seen regularly in case work since 2018. Of the total 133 deaths, 95 were considered drug related deaths by forensic pathologists with at least one additional CNS depressant also present capable of contributing to death. All deaths involved other (non-benzodiazepine) CNS active drugs, although many involved multiple NBz, with five or more different benzodiazepines detected in eight cases.

Bromazolam in Impaired Driving Investigations.

The designer benzodiazepine bromazolam is increasingly encountered in forensic casework, including impaired driving investigations. A series of suspected impaired driving cases that tested positive for bromazolam are described herein along with information about driving performance, driver appearance and observed behavior. Bromazolam was indicated in casework either through screening by liquid chromatography time of flight mass spectrometry (LC-TOF/MS) and/or a positive benzodiazepine immunoassay screen. Blood samples were forwarded for quantitative confirmatory analysis using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method with a reporting limit of 2.0 ng/mL. Bromazolam was reported in 98 impaired driving cases from samples reported between January 2021 and December 2023, with the earliest detection from September 2020. Mean and median blood concentrations were 125 ± 145 ng/mL and 84 ng/mL respectively, with a range of 4.2 - 990 ng/mL. Additional positive findings were reported in almost all cases, with the highest result (990 ng/mL) being the only case in which bromazolam was the only finding. Fentanyl was the most frequent drug found in combination with bromazolam. Driving behaviors reported in these cases included erratic driving, errors in Standardized Field Sobriety Tests (SFSTs), and symptoms consistent with Central Nervous System (CNS) depressants, including slurred speech, incoordination, and lethargic behavior. Based on its prevalence and demonstrated impairing effects, bromazolam should be included in the scope of impaired driving testing as long as it continues to be prevalent in the drug supply.

Increased Pneumonia Risk Associated with Concomitant Use of Inhaled Corticosteroids and Benzodiazepines: A Pharmacovigilance Analysis.

BACKGROUND: Inhaled corticosteroids (ICS) are effective in managing asthma and chronic obstructive pulmonary disease (COPD) but increase the risk of pneumonia. Benzodiazepines (BZD), commonly prescribed for comorbid psychiatric disorders in asthma or COPD patients, are also associated with pneumonia. This study investigates the risk of pneumonia associated with the concomitant use of ICS and BZD. METHODS: Data from the FDA Adverse Event Reporting System from Q4 2013 to Q3 2023 were extracted. Reports involving asthma or COPD patients were included. Disproportionality analysis and logistic regression analysis were performed to assess the risk of pneumonia associated with the combined use of ICS and BZD. Additive and multiplicative models were used to further confirm the results. Additionally, subgroup analyses were conducted based on gender, age, and disease type. RESULTS: A total of 238,411 reports were included. The combined use of ICS and BZD was associated with a higher reporting of pneumonia (ROR: 2.41, 95% CI 2.25-2.58). Using additive and multiplicative methods, the results remained significant. The strongest risk signals were observed in specific drug combinations, such as mometasone with clonazepam, budesonide with temazepam, and mometasone with zopiclone. Subgroup analyses showed higher pneumonia risks in females, patients over 60 years old, and those with asthma. CONCLUSION: Our findings identified a significantly elevated pneumonia risk with the combined use of ICS and BZD. These results highlighted the necessity for cautious co-prescription of ICS and BZD and suggested the need for more comprehensive clinical studies to assess this interaction.

Case Report of Retarded Catatonia: Always Consider Catatonia as a Differential Diagnosis of Altered Mental Status.

BACKGROUND: Catatonia is a rare neuropsychiatric condition; it is estimated that around 10% of patients with mood disorders present signs and symptoms of catatonia. A catatonic syndrome is characterised by mutism, negativism, rigidity, and stupor. CASE REPORT: We report the case of a 59-year-old patient with a medical history of bipolar disorder who was admitted to the internal medicine service due to a seizure episode. During hospitalisation, the patient presented significant worsening of her clinical condition, showing marked symptoms of stupor and catatonia. Once the neurological and metabolic etiologies of altered mental status had been ruled out, pharmacological treatment with high doses of lorazepam was started. The patient had a complete clinical remission, and her evolution was favourable without any complications. Electroconvulsive therapy was recommended as a definitive treatment. CONCLUSIONS: The diagnosis of catatonia is a challenge for both hospitalists and psychiatrists due to the clinical presentation of catatonia. In reporting this clinical case, we want to emphasise the importance of taking into account the catatonic syndrome in our differential diagnoses in patients with altered mental status.

'We need more support and doctors that understand the process of tapering ': A content analysis of free-text responses to a questionnaire on discontinuing long-term benzodiazepine receptor agonist use.

BACKGROUND: Many individuals worldwide continue to take benzodiazepine receptor agonists (BZRAs) long term (≥3 months). The aim of this study was to conduct a content analysis of the views and experiences of discontinuing long-term BZRA use as documented in the free-text responses of respondents to an online questionnaire examining mediators of behaviour change relating to the discontinuation of long-term BZRA use. DESIGN: The questionnaire was disseminated via online BZRA support groups to community-based adults with either current or previous experience of long-term BZRA use. The four free-text questions focused on (1) barriers and (2) facilitators to discontinuing BZRA use; (3) additional supports required to discontinue BZRA use; and (4) additional comments regarding BZRA use. Response data were analysed using summative content analysis. RESULTS: The most commonly reported barrier to BZRA discontinuation related to the consequences of stopping the medication, including withdrawal symptoms and the possibility of return of the original symptoms. The most common facilitator that respondents reported would help them in discontinuing BZRA use was support, primarily from medical professionals. Many respondents reported having been harmed or negatively affected in some way because of BZRA use. Several respondents expressed regret over ever taking BZRAs and/or reported that, with the benefit of hindsight, they should never have taken BZRAs in the first instance. CONCLUSION: The findings highlight the range of barriers faced by those attempting BZRA discontinuation and the importance of additional supports. Holistic and person-centred approaches are needed to support discontinuation of long-term BZRA use that considers an individual's personal circumstances and wider social context. PATIENT OR PUBLIC CONTRIBUTION: 'Experts by experience' with previous experience of long-term BZRA use were involved in developing the questionnaire and writing the manuscript as collaborators. Individuals with lived experience of taking BZRAs completed the questionnaire.

Brief Report: A population-based study of the impact of the COVID-19 pandemic on benzodiazepine use among children and young adults.

The COVID-19 pandemic was associated with increases in the prevalence of depression and anxiety among children and young adults. We studied whether the pandemic was associated with changes in prescription benzodiazepine use. We conducted a population-based study of benzodiazepine dispensing to children and young adults ≤ 24 years old between January 1, 2013, and June 30, 2022. We used structural break analyses to identify the pandemic month(s) when changes in prescription benzodiazepine dispensing occurred, and interrupted time series models to quantify changes in dispensing following the structural break and compare observed and expected benzodiazepine use. A structural break occurs where there is a sudden change in the trend of a time series. We observed an immediate decline in benzodiazepine dispensing of 23.6 per 100,000 (95% confidence interval [CI]: -33.6 to -21.2) associated with a structural break in April 2020, followed by a monthly decrease in the trend of 0.3 per 100,000 (95% CI: -0.74 to 0.14). Lower than expected benzodiazepine dispensing rates were observed each month of the pandemic from April 2020 onward, with relative percent differences ranging from - 7.4% (95% CI: -10.1% to - 4.7%) to -20.9% (95% CI: -23.2% to -18.6%). Results were generally similar in analyses stratified by sex, age, neighbourhood income quintile, and urban versus rural residence. Further research is required to understand the clinical implications of these findings and whether these trends were sustained with further follow-up.

Prevalence and clinical correlates of benzodiazepine use in the patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a serious and disabling condition characterized by abnormal mood changes. Clinical guidelines for depression treatment recommend antidepressant medications, with benzodiazepines acting as short-term synergists. However, little is currently known about the prevalence and associated clinical risk factors of benzodiazepine use among Chinese patients with MDD. This study aimed to explore the prevalence and clinical risk factors associated with benzodiazepine use in this population. METHODS: A total of 2742 patients with MDD (males/females = 816/1926, aged 14-60 years) participated in this cross-sectional observational study. General information and psychosis assessments were collected online. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), anxiety symptoms using the Generalized Anxiety Disorder-7 (GAD-7), and sleep problems and suicidal tendencies using the third and ninth items of the PHQ-9. Multivariable logistic regression analysis models were employed to identify factors associated with benzodiazepine use. RESULTS: The prevalence of benzodiazepine use among patients with MDD was 42.9 %. Among these patients, 99.6 % used a single benzodiazepine, with oxazepam being the most frequently prescribed. Age, severity of sleep problems, depressive symptoms, and anxiety symptoms were significantly correlated with benzodiazepine use (all P < 0.001). LIMITATIONS: The cross-sectional design of this study precludes establishing causal relationships. CONCLUSION: Our findings indicate a high prevalence of benzodiazepine use among Chinese patients with MDD. Factors such as severe depressive symptoms, anxiety symptoms, age, and sleep problems appear to be associated with benzodiazepine use. These results underscore the importance of vigilance regarding benzodiazepine use in patients with MDD.

Barriers to, and Facilitators of, Checking Drugs for Adulterants in the Era of Fentanyl and Xylazine: Qualitative Study.

BACKGROUND: Overdose deaths continue to reach new records in New York City and nationwide, largely driven by adulterants such as fentanyl and xylazine in the illicit drug supply. Unknowingly consuming adulterated substances dramatically increases risks of overdose and other health problems, especially when individuals consume multiple adulterants and are exposed to a combination of drugs they did not intend to take. Although test strips and more sophisticated devices enable people to check drugs for adulterants including fentanyl and xylazine prior to consumption and are often available free of charge, many people who use drugs decline to use them. OBJECTIVE: We sought to better understand why people in the New York City area do or do not check drugs before use. We plan to use study findings to inform the development of technology-based interventions to encourage consistent drug checking. METHODS: In summer 2023, team members who have experience working with people who use drugs conducted 22 semistructured qualitative interviews with a convenience sample of people who reported illicit drug use within the past 90 days. An interview guide examined participants' knowledge of and experience with adulterants including fentanyl, xylazine, and benzodiazepines; using drug testing strips; and whether they had ever received harm reduction services. All interviews were audio recorded, transcribed, and analyzed for emerging themes. RESULTS: Most participants lacked knowledge of adulterants, and only a few reported regularly checking drugs. Reasons for not checking included lacking convenient access to test supplies, or a place to check samples out of the public's view, as well as time considerations. Some participants also reported a strong belief that they were not at risk from fentanyl, xylazine, or other adulterants because they exclusively used cocaine or crack, or that they were confident the people they bought drugs from would not sell them adulterated substances. Those who did report testing their drugs described positive interactions with harm reduction agency staff. CONCLUSIONS: New forms of outreach are needed not only to increase people's knowledge of adulterated substances and awareness of the increasing risks they pose but also to encourage people who use drugs to regularly check their substances prior to use. This includes new intervention messages that highlight the importance of drug checking in the context of a rapidly changing and volatile drug supply. This messaging can potentially help normalize drug checking as an easily enacted behavior that benefits public health. To increase effectiveness, messages can be developed with, and outreach can be conducted by, trusted community members including people who use drugs and, potentially, people who sell drugs. Pairing this messaging with access to no-cost drug-checking supplies and equipment may help address the ongoing spiral of increased overdose deaths nationwide.