Association Between Benzodiazepine Use With or Without Opioid Use and All-Cause Mortality in the United States, 1999-2015

Xu, Kevin Y; Hartz, Sarah M.; Borodovsky, Jacob T.; Bierut, Laura J.; Grucza, Richard A.

doi:10.1001/jamanetworkopen.2020.28557

Cited by 65 publications

(43 citation statements)

References 38 publications

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“…Although this approach may be effective for managing anxiety, it is also associated with significant risks of fatal and nonfatal overdoses. 8,[61][62][63] To optimize safety, alternative approaches to treating anxiety and depression-pharmacological or nonpharmacological-should be considered when opioids are also prescribed. The coprescribing of benzodiazepines and opioids, when deemed appropriate, should be carefully monitored.…”

Section: Discussionmentioning

confidence: 99%

Safety of opioid prescribing among older cancer survivors

Salz

Mishra

Gennarelli

et al. 2021

Cancer

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BACKGROUND:Cancer survivors receive more long-term opioid therapy (LTOT) than people without cancer, but the safety of LTOT prescribing is unknown. METHODS: Opioid-naive adults aged ≥66 years who had been diagnosed in 2008-2015 with breast, lung, head and neck, or colorectal cancer were identified with data from Surveillance, Epidemiology, and End Results cancer registries linked with Medicare claims. Survivors with 1 or more LTOT episodes (≥90 consecutive days) occurring ≥1 year after their cancer diagnosis and before censoring at hospice entry, another cancer diagnosis, 6 months before death, or December 2016 were included. The safety of prescribing during the first 90 days of the first LTOT episode was measured during follow-up. As a positive safety indicator, the proportion of survivors with concurrent nonopioid pain management was measured. Indicators of less safe prescribing were the proportion of survivors with a high average daily opioid dose (≥90 morphine milligram equivalents) and the proportion of survivors with concurrent benzodiazepine dispensing. Multivariable logistic regression analyses were conducted to identify clinical predictors of each safety outcome. RESULTS: In all, 3628 cancer survivors received LTOT during follow-up (median duration, 4.9 months; interquartile range, 3.5-8.0 months). Seventy-two percent of the survivors received multimodal pain management concurrently with LTOT. Eight percent of the survivors had high-dose opioid prescriptions; 25% of the survivors received benzodiazepines during LTOT. Multivariable analyses identified variations in safety measures by multiple clinical factors, although none were consistently significant across outcomes. CONCLUSIONS: To improve safe LTOT prescribing for survivors, efforts should focus on increasing multimodal pain management and reducing inappropriate benzodiazepine prescribing. Different clinical predictors of each outcome suggest different drivers of safe prescribing.

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Section: Discussionmentioning

confidence: 99%

Safety of opioid prescribing among older cancer survivors

Salz

Mishra

Gennarelli

et al. 2021

Cancer

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“…We found that 70.9% of new persistent opioid users lled a sedative-hypnotic prescription during the study period as well, while 98.2% of new persistent sedativehypnotic users lled an opioid prescription. Sedative-hypnotics are known to potentiate the respiratory depressive effects of opioids [33], and concomitant opioid and sedative-hypnotic use has been associated with increased rates of long-term opioid use, opioid overdose and all-cause mortality [34][35][36][37]. In particular, pre-operative sedative-hypnotic use among opioid-naïve patients increases the risk of long-term opioid use post-operatively [38].…”

Section: Discussionmentioning

confidence: 99%

New and persistent controlled substance use among patients undergoing mastectomy and reconstructive surgery

Cogan

Raghunathan

Beauchemin

et al. 2021

Breast Cancer Res Treat

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Prolonged use of controlled substances can place patients at increased risk of dependence and complications. Women who have mastectomy and reconstructive surgery (M+R) may be vulnerable to becoming new persistent users (NPUs) of opioid and sedative-hypnotic medications. MethodsUsing the MarketScan health care claims database, we identi ed opioid-and sedative-hypnotic-naïve women who had M+R from 2008-2017. Women who lled ≥1 peri-operative prescription and ≥2 post-operative prescriptions within one year after surgery were classi ed as NPUs. Univariate and multivariable logistic regression analyses were used to estimate rates of new persistent use and predictive factors. Risk summary scores were created based on the sum of associated factors. ResultsWe evaluated 25,270 opioid-naïve women and 27,651 sedative-hypnotic-naïve women.We found that 18,931 opioid-naïve women lled a peri-operative opioid prescription, and of those, 3,315 (17.5%) became opioid NPUs postoperatively. Additionally, 10,781 sedative-hypnotic-naïve women lled a peri-operative sedative-hypnotic prescription, and of those, 1,837 (17.0%) became sedative-hypnotic NPUs. Development of new persistent sedative-hypnotic use was associated with age ≤49 (OR 1.79 [95% CI 1.43-2.25]) and age 50-64 (1.65 [1.31-2.07]) compared to age ≥65; Medicaid insurance (1.92 [1.23-2.98]); southern residence (1.38 [1.20-1.59]); breast cancer diagnosis (1.78 [1.09-2.91]); and chemotherapy (2.24 [2.02-2.49]). Risk of NPU increased with higher risk score. Women with ≥3 of these risk factors were three times more likely to become sedative-hypnotic NPUs than patients with 0 or 1 factors (3.03 [2.60-3.53]). Comparable ndings were seen regarding new persistent opioid use. ConclusionWomen who have M+R are at risk of developing both new persistent opioid and new persistent sedative-hypnotic use. A patient's risk of becoming an NPU increases as their number of risk factors increases. Non-pharmacologic strategies are needed to manage pain and anxiety following cancer-related surgery.

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“…The fact that patients in plans with PA were much less likely to be co-prescribed benzodiazepines may reflect algorithms to identify co-prescribing of benzodiazepines and buprenorphine-naloxone and programs to reduce such co-prescribing [20]. Co-prescribing of opioids with benzodiazepines is associated with a higher mortality risk [21,22]. The label for buprenorphine-naloxone (brand name Suboxone) states that prescribers should '[u]se caution in prescribing SUBOXONE sublingual tablet for patients receiving benzodiazepines or other CNS depressants and warn patients against concomitant selfadministration/misuse'.…”

Section: Discussionmentioning

confidence: 99%

The association of Medicare Part D prior authorization for buprenorphine–naloxone with adherence to opioid use disorder treatment guidelines in the United States

et al. 2021

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Aims To assess differences in the quality of opioid use disorder (OUD) treatment received by Medicare beneficiaries enrolled in health plans that used prior authorization (PA) for buprenorphine–naloxone compared with those enrolled in plans that did not use PA. Design, Setting and Participants Cross‐sectional observational study, United States. Continuously enrolled beneficiaries (71 294) with an OUD who filled at least one prescription for buprenorphine–naloxone between March 2012 and July 2017. Measurements Percentage of patients tested for hepatis B, hepatis C, HIV and liver functioning; percentage of patients with urine drug screens and number of urine drug screens; continuous use of buprenorphine–naloxone for at least 180 days; co‐use of benzodiazepines; number of outpatient visits with and without an OUD diagnosis. Findings PA was significantly associated with a lower likelihood of testing for hepatitis B [−3.5, 95% confidence interval (CI) = −4.4, −2.7] and C (−5.9, 95% CI = −6.9, −4.9), but the findings were inconclusive as to whether or not there was a difference in HIV (−1.1, 95% CI = −2.5, 0.4) or liver function testing (1.3, 95% CI = −0.1, 2.7). PA was associated with a lower likelihood of urine drug screening (−25.5, 95% CI = −26.8, −24.1) and with fewer drug screens (−2.5, 95% CI = −3.0, −2.1). Findings were inconclusive as to whether or not there was a difference in continuous use of buprenorphine–naloxone (0.3, 95% CI = −1.2, 1.8). PA was associated with fewer outpatient visits (−2.1, 95% CI = −3.0, −1.2) and fewer outpatient visits with an OUD diagnosis (−1.7, 95% CI = −2.1, −1.3). PA was associated with a lower likelihood of filling benzodiazepine prescriptions before and after buprenorphine–naloxone induction (−28.9, 95% CI = −29.6, −28.3) but a greater likelihood of only using benzodiazepines after buprenorphine–naloxone induction (10.6, 95% CI = 9.3, 11.8). Conclusions US Medicare patients subject to prior authorization for buprenorphine–naloxone are not more likely to receive high‐quality treatment for opioid use disorder than patients not subject to prior authorization.

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Association Between Benzodiazepine Use With or Without Opioid Use and All-Cause Mortality in the United States, 1999-2015

Cited by 65 publications

References 38 publications

Safety of opioid prescribing among older cancer survivors

Safety of opioid prescribing among older cancer survivors

New and persistent controlled substance use among patients undergoing mastectomy and reconstructive surgery

The association of Medicare Part D prior authorization for buprenorphine–naloxone with adherence to opioid use disorder treatment guidelines in the United States

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