Concurrent use of opioids with benzodiazepines or nonbenzodiazepine sedatives among patients with cancer referred to an outpatient palliative care clinic

Abstract

Background The concurrent use of opioids with benzodiazepines (BZD) or nonbenzodiazepine sedatives (S) recently was found to be associated with an increased risk of overdose death compared with the use of opioids alone. In the current study, the authors examined the frequency and trend of concurrent opioid/BZD‐S use and its associated risk factors among patients with cancer. Methods Data regarding the frequency and trend of concurrent opioid/BZD‐S use were extracted for 1500 randomly selected patients referred to the outpatient palliative care clinic at The University of Texas MD Anderson Cancer Center between the calendar years of 2011 and 2016. To explore associated risk factors, the authors compared the demographic and clinical predictors of 418 patients each in the concurrent opioid/BZD‐S group and opioids‐only group. Results In 2011, at the time of referral to the palliative care clinic, 96 of 221 patients with cancer (43%) were prescribed concurrent opioids/BZD‐S. This rate progressively declined to 67 of 217 patients (31%) by 2016 (P = .0008). Patients in the concurrent opioid/BZD‐S group had a higher percentage of females (233 individuals; 55% [P = .007]) and whites (323 individuals; 77% [P = .002]), and patients reported higher scores regarding depression (P = .0001), anxiety (P ≤ .0001), drowsiness (P = .048), and worst feeling of well‐being (P = .001). The morphine equivalent daily dose was significantly higher in concurrent opioid/BZD‐S group (median of 67.5 mg/day [interquartile range (IQR), 30‐135 mg/day] vs 60 mg/day [IQR, 30‐105 mg/day]; P = .034). Multivariate analysis demonstrated that anxiety (P ≤ .0001), white race (P = .0092), and poor Eastern Cooperative Oncology Group performance status (P = .0017) were significantly associated with concurrent use. Conclusions The concurrent use of opioids with BZD‐S has declined but continues to be frequent among patients with cancer. Anxiety, white race, and poor Eastern Cooperative Oncology Group performance status were associated with its use. More research is needed to explore which medications can replace these agents.

The Status and Prescription Patterns of Opioid Utilization in a Large Comprehensive Teaching Hospital in China According to the Anatomical Therapeutic Chemical Classification/Defined Daily Dose Methodology

“…Given that there is no international standard for measuring the level of hospital opioid consumption, comparisons were made between our collected data and existing foreign published studies on drug utilization and opioid consumption evaluations in hospital settings based on the ATC/DDD system. We confirmed the hypothesis of our study, that is, opioid consumption at this hospital was relatively low compared with the consumption rates reported in other studies, which included two hospitals and four databases from Europe, East Asia, and North America (12)(13)(14)(15)(16)(17). One study using the same measurement unit (DDD/100 bed-days), carried out in a hospital in Madrid, Spain, revealed that opioid consumption had a remarkable increasing tendency, from 22.3 DDD/100 bed-days in 2011 to 26.5 DDD/100 beddays in 2015 (16).…”

Safety of opioid prescribing among older cancer survivors

“…59 Our larger, nationally representative sample found a higher rate (25%) of benzodiazepine coprescribing during LTOT among breast cancer survivors, and this elevates concern for this population. A study by Haider et al 60 found that 31% of patients with cancer receiving opioids in a palliative care clinic also received benzodiazepines. Similarly to our findings, Haider et al found higher rates of coprescribing of benzodiazepines and opioids among patients with anxiety and depression, and this reflected the use of benzodiazepines to manage these issues.…”

Optimization of opioid utility in cancer pain populations

“…Note US FDA warning of the risk of serious breathing difficulties in patients taking central nervous system depressants (including opioids) concurrently with gabapentin or pregabalin (34) Concurrent use of gabapentin has been associated with an increased risk of opioid-related death (35) Concurrent use of benzodiazepines has been associated with up to 5-fold increased risk of opioid overdose-association death (36) Strong opioids Co-administration of pregabalin increases the risk of somnolence or dizziness vs. pregabalin alone (37) Morphine Morphine-induced gastrointestinal hypomotility may increase pregabalin absorption (37) Breakthrough pain -Cancer patients who are prescribed a baseline sustained-release opioid may also require an on-demand immediate-release opioid for rescue situations such as breakthrough pain (38,39) Inadequate analgesia and/or drug tolerance -For opioid rotation, consider a two-step dose-reduction and re-titration approach for adjusting to differences in side effects and pharmacokinetics (40,41) authors failed to find clinically relevant sex difference in opioid-induced respiratory depression. However, there were higher rates of respiratory events reported for five opioids in patients ≥70 years, underlining the need for careful dosing in older people.…”

“…The concurrent use of opioids with benzodiazepines, which is still common in cancer patients, has been associated with a risk of overdose-associated death up to 5-fold greater than for opioids alone (36).…”