Concurrent use of benzodiazepines, antidepressants, and opioid analgesics with zolpidem and risk for suicide: a case–control and case–crossover study

Sung, Hi Gin; Li, Junquing; Nam, Jin Hyun; Won, Dae Yeon; Choi, BongKyoo; Shin, Ju‐Young

doi:10.1007/s00127-019-01713-x

Cited by 8 publications

(6 citation statements)

References 44 publications

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“…The result on DDD seems consistent to the rationale that using lower doses of two or more drugs could achieve efficacy with less severe side effects than would be expected from higher dosage of a single drug [37][38][39]. However, there is no evidence that poly-therapy had lower side effects than monotherapy [10][11][12], thus limiting BZD/Z-drugs dose is crucial [25]. Findings on duration of BZD/Z-drug use and on age of first use support current recommendations to limit their prescription, the duration of use, and to delay the beginning of these treatments as much as possible.…”

Section: Et Al / Mono-and Poly-therapy With Benzodiazepines or Z-drugssupporting

confidence: 61%

“…Poly-therapy users are more prevalent than mono-therapy users when the duration of the treatment is longer or the dose is higher [4,6,8,9]. Poly-therapy users have higher rates of adverse events, toxicity, harmful drug-to drug interactions, and increased risk of mortality, including the one due to suicide, than mono-therapy users [10][11][12]. Polytherapy users are highly represented among Substance Use Disorder (SUD) patients, with 34.6% using more than one BZD and 20% using both BZDs and Z-drugs [9].…”

Section: Introductionmentioning

confidence: 99%

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Mono- and poly-therapy with benzodiazepines or Z-drugs: Results from a tertiary-care Addiction Unit study

Mansueto

Lugoboni

Casari

et al. 2021

JRS

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BACKGROUND: Using benzodiazepines (BZDs) or Z-drugs in poly-therapy is a critical issue. OBJECTIVE: Identifying factors influencing the use of BZDs/Z-drugs in poly- vs mono-therapy in patients with or without substance use disorders (SUDs). METHODS: 986 inpatients were analysed. Socio-demographic and clinical variables were collected. BZD/Z-drug doses were compared via the Defined Daily Dose (DDD) and standardized as diazepam dose equivalents. Mann-Whitney, Chi-square, Fisher test, hierarchical multivariate regression analyses were run referring to the whole sample and to subjects with current SUDs, lifetime SUDs, current and lifetime SUDs, non-SUDs. RESULTS: In the whole sample the variance of being mono- vs poly-therapy users was explained by BZD/Z-drug formulation, DDD, duration of treatment, age of first BZDs/Z-drugs use (ΔR2 = 0.141, p < 0.001). Among those with current SUDs (ΔR2 = 0.278, p = 0.332) or current and lifetime SUDs (ΔR2 = 0.154, p = 0.419), no variables explained the variance of being mono-vs poly-therapy users. Among lifetime SUDs subjects, the variance of being mono- vs poly-therapy users was explained by BZD/Z-drug formulation and age of first BZD/Z-drug use (ΔR2 = 0.275, p < 0.001). Among non-SUDs subjects, the variance of being mono- vs poly-therapy users was explained by DDD and duration of treatment (ΔR2 = 0.162, p = 0.001). CONCLUSIONS: Tablets, high drug doses, long duration of treatment, and early age of first use were more likely associated to poly- than mono-therapy. This suggests that patients have different clinical features and a pharmacological prescription should be tailored to them also based on the variables here analysed.

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Section: Et Al / Mono-and Poly-therapy With Benzodiazepines or Z-drugssupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Mono- and poly-therapy with benzodiazepines or Z-drugs: Results from a tertiary-care Addiction Unit study

Mansueto

Lugoboni

Casari

et al. 2021

JRS

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“…Of the 114 included articles, the case‐crossover design was the most common (100, 88%), 18–117 followed by the case‐time‐control (19, 17%), 38,63,67,71,86,118–131 and case‐case‐time‐control (4, 3%) 33,47,48,86 . (Table 1) The most common outcomes measured in these studies were hospitalization (43, 38%), cardiovascular events (22, 19%) and fall‐related injury/fracture (15, 13%).…”

Section: Resultsmentioning

confidence: 99%

“…10 Of 48 articles that used multiple control windows, half of the articles reported no washout period between each control period. 19,24,25,27,28,37,39,41,44,46,53,55,59,66,72,73,77,79,81,84,90,103,104,106,113,114 It is unclear whether these multiple control windows were analyzed as a single large control window or time-dependent control windows.…”

Section: Publication Yearmentioning

confidence: 99%

Evaluating the use of methods to mitigate bias from non‐transient medications in the case‐crossover design: A systematic review

Huang

Tadrous

et al. 2023

Pharmacoepidemiology and Drug

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Purpose The case‐crossover design is a self‐controlled study design used to compare exposure immediately preceding an event occurrence with exposure in earlier control periods. The design is most suitable for transient exposures in order to avoid biases that can be problematic when using the case‐crossover design for non‐transient (i.e., chronic) exposures. Our goal was to conduct a systematic review of case‐crossover studies and its variants (case‐time‐control and case‐case‐time‐control) in order to compare design and analysis choices by medication type. Methods We conducted a systematic search to identify recent case‐crossover, case‐time‐control, and case‐case‐time‐control studies focused on medication exposures. Articles indexed in MEDLINE and EMBASE using these study designs that were published between January 2015 and December 2021 in the English language were identified. Reviews, methodological studies, commentaries, articles without medications as the exposure of interest, and articles with no available full text were excluded. Study characteristics including study design, outcome, risk window, control window, reporting of discordant pairs, and inclusion of sensitivity analyses were summarized overall and by medication type. We further evaluated the implementation of recommended methods to account for biases introduced by non‐transient exposures among articles that used the case‐crossover design on a non‐transient exposure. Results Of the 2036 articles initially identified, 114 articles were included. The case‐crossover was the most common study design (88%), followed by the case‐time‐control (17%), and case‐case‐time‐control (3%). Fifty‐three percent of the articles included only transient medications, 35% included only non‐transient medications, and 12% included both. Across years, the proportion of case‐crossover articles evaluating a non‐transient medication ranged from 30% in 2018 to 69% in 2017. We found that 41% of the articles that evaluated a non‐transient medication did not apply any of the recommended methods to account for biases and more than half of which were conducted by authors with no previous publication history of case‐crossover studies. Conclusion Using the case‐crossover design to evaluate a non‐transient medication remains common in pharmacoepidemiology. Researchers should apply appropriate design and analysis choices when opting to use a case‐crossover design with non‐transient medication exposures.

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“…To account for the fact that sicker individuals have a higher risk of opioid-related events, the Charlson Comorbidity Index was used 27. Benzodiazepines,28 muscle relaxants,29 hypnotics,30 antidepressants,31 and gabapentinoids32 have been shown to increase the risk of opioid-related adverse outcomes and were used in the adjusted analyses. Mental health disorders are strongly correlated with substance use disorders and opioid overdose 33.…”

Section: Methodsmentioning

confidence: 99%

Comparative Study of Opioid Initiation With Tramadol, Short-acting Hydrocodone, or Short-acting Oxycodone on Opioid-related Adverse Outcomes Among Chronic Noncancer Pain Patients

Acharya

Hayes

et al. 2022

The Clinical Journal of Pain

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Objective: To compare the safety profiles of low and high-dose tramadol, short-acting hydrocodone, and short-acting oxycodone therapies among chronic noncancer pain individuals. Materials and Methods:A retrospective cohort study of individuals with back/neck pain/osteoarthritis with an initial opioid prescription for tramadol, hydrocodone, or oxycodone was conducted using IQVIA PharMetrics Plus claims for Academics database (2006 to 2020). Two cohorts were created for separately studying opioid-related adverse events (overdoses, accidents, self-inflicted injuries, and violence-related injuries) and substance use disorders (opioid and nonopioid). Patients were followed from the index date until an outcome event, end of enrollment, or data end. Time-varying exposure groups were constructed and Cox regression models were estimated.Results: A total of 1,062,167 (tramadol [16.5%], hydrocodone [61.1%], and oxycodone [22.4%]) and 986,809 (tramadol [16.5%], hydrocodone [61.3%], and oxycodone [22.2%]) individuals were in the adverse event and substance use disorder cohorts. All high-dose groups had elevated risk of nearly all outcomes, compared with low-dose hydrocodone. Compared with low-dose hydrocodone, low-dose oxycodone was associated with a higher risk of opioid overdose (hazard ratio: 1.79 [1.37 to 2.33]). No difference in risk was observed between low-dose tramadol and low-dose hydrocodone (hazard ratio: 0.85 [0.64 to 1.13]). Low-dose oxycodone had higher risks of an opioid use disorder, and low-dose tramadol had a lower risk of accidents, self-inflicted injuries, and opioid use disorder compared with low-dose hydrocodone.Discussion: Low-dose oxycodone had a higher risk of opioid-related adverse outcomes compared with low-dose tramadol and hydrocodone. This should be interpreted in conjunction with the benefits of pain control and functioning associated with oxycodone use in future research.

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Concurrent use of benzodiazepines, antidepressants, and opioid analgesics with zolpidem and risk for suicide: a case–control and case–crossover study

Cited by 8 publications

References 44 publications

Mono- and poly-therapy with benzodiazepines or Z-drugs: Results from a tertiary-care Addiction Unit study

Mono- and poly-therapy with benzodiazepines or Z-drugs: Results from a tertiary-care Addiction Unit study

Evaluating the use of methods to mitigate bias from non‐transient medications in the case‐crossover design: A systematic review

Comparative Study of Opioid Initiation With Tramadol, Short-acting Hydrocodone, or Short-acting Oxycodone on Opioid-related Adverse Outcomes Among Chronic Noncancer Pain Patients

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