Comparison of toxicity associated with nonmedical use of benzodiazepines with buprenorphine or methadone

Lee, Samantha C.; Klein‐Schwartz, Wendy; Doyon, Suzanne; Welsh, Christopher

doi:10.1016/j.drugalcdep.2014.02.014

Cited by 36 publications

(30 citation statements)

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“…5 Patients with opioid use disorders have a higher risk of overdose death-both suicide and non-suicide-when taking benzodiazepines. 6,7,35 Senior patients are particularly vulnerable, because benzodiazepines are associated with falls, [36][37][38][39] hip fractures, 12 delirium, 10,11 disability, 13 dementia, 14,15 and motor vehicle accidents. 40 Osteoporosis has been linked to fractures alongside benzodiazepine prescriptions in The referent for odds ratios for diagnoses and other prescriptions is patients who did not have that diagnosis or prescription patients at risk of falls, although no direct relationship between osteoporosis and benzodiazepine prescriptions has been described.…”

Section: Discussionmentioning

confidence: 99%

“…We extracted medical diagnoses defined by the Healthcare Effectiveness Data and Information Set (HEDIS; asthma, COPD, cardiovascular disease, depression, diabetes, hypertension, obesity, osteoporosis, and tobacco use), 30 psychiatric diagnoses for which benzodiazepines are commonly prescribed (anxiety and insomnia), and diagnoses for which benzodiazepines are contraindicated or controversial (alcohol abuse, sleep apnea, and substance abuse). 6,7,9,31 We also extracted data about antidepressant medication prescribing from the EHR, because these are commonly considered first-line agents for depression and anxiety. We included the antidepressants fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, mirtazapine, bupropion, venlafaxine, desvenlafaxine, duloxetine, nefazodone, amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, nortriptyline, protriptyline, trimipramine, phenelzine, tranylcypromine, isocarboxazid, trazodone, and vilazodone.…”

Section: Data Extractionmentioning

confidence: 99%

“…3,4 National registries in Europe and the United States have linked benzodiazepines use to elevated rates of respiratory suppression in patients with chronic obstructive pulmonary disease (COPD) 5 and with overdose death in substance use disorders. 6,7 Benzodiazepines may also be linked to cancer risk and to exacerbation of obstructive sleep apnea (OSA) severity. 8,9 In the elderly, benzodiazepines are associated with delirium in the hospital 10,11 and with hip fractures, 12 disability, 13 and dementia 14,15 in the community.…”

Section: Introductionmentioning

confidence: 99%

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Benzodiazepines are Prescribed More Frequently to Patients Already at Risk for Benzodiazepine-Related Adverse Events in Primary Care

et al. 2016

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BACKGROUND: Benzodiazepine use is associated with adverse drug events and higher mortality. Known risk factors for benzodiazepine-related adverse events include lung disease, substance use, and vulnerability to fracture. OBJECTIVE: To determine whether benzodiazepine prescribing is associated with risk factors for adverse outcomes. DESIGN: Longitudinal cohort study between July 1, 2011, and June 30, 2012. PARTICIPANTS: Patients who visited hospital-and community-based practices in a primary care practicebased research network. MAIN MEASURES:Odds ratio of having a target medical diagnosis for patients who received standard and highdose benzodiazepine prescriptions; rates per 100 patients for outpatient and emergency department visits and hospitalizations. KEY RESULTS: Among 65,912 patients, clinicians prescribed at least one benzodiazepine to 15 % (9821). Of benzodiazepine recipients, 5 % received high doses. Compared to non-recipients, benzodiazepine recipients were more likely to have diagnoses of depression (OR, 2.7; 95 % CI, 2.6-2.9), substance abuse (OR, 2.2; 95 % CI, 1.9-2.5), tobacco use (OR, 1.7; 95 % CI, 1.5-1.8), osteoporosis (OR, 1.6; 95 % CI, 1.5-1.7), chronic obstructive pulmonary disease (OR, 1.6; 95 % CI, 1.5-1.7), alcohol abuse (OR, 1.5; 95 % CI, 1.3-1.7), sleep apnea (OR, 1.5; 95 % CI, 1.3-1.6), and asthma (OR, 1.5; 95 % CI, 1.4-1.5). Compared to low-dose benzodiazepine recipients, high-dose benzodiazepine recipients were even more likely to have certain medical diagnoses: substance abuse (OR, 7.5; 95 % CI, 5.5-10.1), alcohol abuse (OR, 3.2; 95 % CI, 2.2-4.5), tobacco use (OR, 2.7; 95 % CI, 2.1-3.5), and chronic obstructive pulmonary disease (OR, 1.5; 95 % CI, 1.2-1.9).Benzodiazepine recipients had more primary care visits per 100 patients (408 vs. 323), specialist outpatient visits (815 vs. 578), emergency department visits (47 vs. 29), and hospitalizations (26 vs. 15; p < .001 for all comparisons). CONCLUSIONS: Clinicians prescribed benzodiazepines and high-dose benzodiazepines more frequently to patients at higher risk for benzodiazepine-related adverse events. Benzodiazepine prescribing was associated with increased healthcare utilization.

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Section: Discussionmentioning

confidence: 99%

Section: Data Extractionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Benzodiazepines are Prescribed More Frequently to Patients Already at Risk for Benzodiazepine-Related Adverse Events in Primary Care

et al. 2016

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“…Opioids and benzodiazepines have complex drug interactions and, in combination, can result in synergistic respiratory depression, 6,8 but the exact mechanisms by which benzodiazepines worsen opioidrelated respiratory depression are not fully understood. 9 Other factors may also contribute to the risk of overdose from co-ingestion of these drugs. People who use benzodiazepines in combination with opioids demonstrate patterns and characteristics that differentiate them from opioid users not taking benzodiazepines.…”

mentioning

confidence: 99%

Emergency Department Visits and Overdose Deaths From Combined Use of Opioids and Benzodiazepines

Jones

McAninch

2015

American Journal of Preventive Medicine

318

245

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“…Unfortunately, it is not always clear which medications may be harmful versus beneficial. Benzodiazepines are associated with worse outcomes with buprenorphine: decreased retention in OUD treatment (Fareed et al, 2014; Ferri et al, 2014; Lee et al, 2014); increased risk of emergency room visits (Schuman-Olivier et al, 2013); accidental overdose; and death (Häkkinen et al, 2012; Reynaud et al, 1998; Sansone and Sansone, 2015; Seldén et al, 2012). …”

Section: Introductionmentioning

confidence: 99%

Psychoactive medications and disengagement from office based opioid treatment (obot) with buprenorphine

Weinstein

Cheng

Quinn

et al. 2017

Drug and Alcohol Dependence

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Background The prevalence of psychoactive medications (PAMs) use in patients enrolled in Office Based Opioid Treatment (OBOT) and its association with engagement in this care is largely unknown. Objective To describe the use of PAMs, including those medications with emerging evidence of misuse (“emerging PAMs” - gabapentin, clonidine and promethazine) among patients on buprenorphine, and its association with disengagement from OBOT. Methods This is a retrospective cohort study of adults on buprenorphine from January, 2002 to February, 2014. The association between use of PAMs and 6-month disengagement from OBOT was examined using multivariable logistic regression models. A secondary analysis exploring time-to-disengagement was conducted using Cox regression models. Results At OBOT entry, 43% of patients (562/1308) were prescribed any PAM; including 17% (223/1308) on an emerging PAM. In separate adjusted analyses, neither the presence of any PAM (adjusted odds ratio [AOR] 1.07, 95% CI [0.78, 1.46]) nor an emerging PAM (AOR 1.28 [0.95, 1.74]) was significantly associated with 6-month disengagement. The results were similar for the Cox model (any PAM (adjusted hazard ratio [AHR] 1.16, 95% CI [1.00, 1.36]), emerging PAM (AHR 1.18 [0.98, 1.41])). Exploratory analyses suggested gabapentin (AHR 1.30 [1.05 – 1.62]) and clonidine (AHR 1.33 [1.01 – 1.73]) specifically, may be associated with an overall shorter time to disengagement. Conclusions Psychoactive medication use is common among patients in buprenorphine treatment. No significant association was found between the presence of any psychoactive medications, including medications with emerging evidence of misuse, and 6-month disengagement from buprenorphine treatment.

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Comparison of toxicity associated with nonmedical use of benzodiazepines with buprenorphine or methadone

Cited by 36 publications

References 50 publications

Benzodiazepines are Prescribed More Frequently to Patients Already at Risk for Benzodiazepine-Related Adverse Events in Primary Care

Benzodiazepines are Prescribed More Frequently to Patients Already at Risk for Benzodiazepine-Related Adverse Events in Primary Care

Emergency Department Visits and Overdose Deaths From Combined Use of Opioids and Benzodiazepines

Psychoactive medications and disengagement from office based opioid treatment (obot) with buprenorphine

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