Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study

Park, Tae Woo; Saitz, Richard; Ganoczy, Dara; Ilgen, Mark A.; Bohnert, Amy S. B.

doi:10.1136/bmj.h2698

Cited by 487 publications

(417 citation statements)

References 30 publications

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“…For example, half of all opioidrelated deaths also involved a benzodiazepine, 18% involved antihistamines, and 9% involved a tricyclic antidepressant. Not only does this suggest a high level of mental health comorbidity in this population, but given the body of research confirming a clinically important interaction between opioids and CNS depressants 10,11 , these findings are of considerable concern. In particular, this suggests that dangerous combinations of medications contribute frequently to accidental fatal opioid overdoses.…”

Section: Opioid Involvementmentioning

confidence: 95%

Latest trends in opioid-related deaths in Ontario

Gomes¹,

Greaves²,

Martins³

et al. 2017

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Section: Opioid Involvementmentioning

confidence: 95%

Latest trends in opioid-related deaths in Ontario

Gomes¹,

Greaves²,

Martins³

et al. 2017

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“…(2) Consistency is the strongest evidence, with 33 of 34 studies showing a positive association of hypnotic consumption and mortality. (3) Several kinds of specificity of hypnotics-mortality associations have been identified: the excess of deaths at night among hypnotics users [21], the excesses of infection [13], COPD [57], and suicide deaths [50], and the excess of specific cancers such as lung and esophagus [38]. (4) The temporality of hypnotic usage preceding death is consistent with causation.…”

Section: Bradford Hill Criteria Of Causation Are Fulfilledmentioning

confidence: 99%

“…For these applications, the mechanisms by which hypnotics hyperpolarize and inhibit respiratory neurons leading to death are well understood at the molecular, cellular, physiologic and organismic levels. Also reported are thousands of overdose deaths per year attributable to hypnotics, with a larger number of cases in which hypnotics as well as opiates and other sedatives are lethal in combination [50][51][52]. It has been suggested that currently, tens of thousands of yearly self-injury deaths are related to hypnotics and sedative use [53].…”

Section: The Causality Of Hypnotics Effects On Mortalitymentioning

confidence: 99%

Mortality Risk of Hypnotics: Strengths and Limits of Evidence

Kripke

2015

Drug Saf

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Sleeping pills, more formally defined as hypnotics, are sedatives used to induce and maintain sleep. In a review of publications for the past 30 years, descriptive epidemiologic studies were identified that examined the mortality risk of hypnotics and related sedative-anxiolytics. Of the 34 studies estimating risk ratios, odds ratios, or hazard ratios, excess mortality associated with hypnotics was significant (p \ 0.05) in 24 studies including all 14 of the largest, contrasted with no studies at all suggesting that hypnotics ever prolong life. The studies had many limitations: possibly tending to overestimate risk, such as possible confounding by indication with other risk factors; confusing hypnotics with drugs having other indications; possible genetic confounders; and too much heterogeneity of studies for meta-analyses. There were balancing limitations possibly tending towards underestimates of risk such as limited power, excessive follow-up intervals with possible follow-up mixing of participants taking hypnotics with controls, missing dosage data for most studies, and over-adjustment of confounders. Epidemiologic association in itself is not adequate proof of causality, but there is proof that hypnotics cause death in overdoses; there is thorough understanding of how hypnotics euthanize animals and execute humans; and there is proof that hypnotics cause potentially lethal morbidities such as depression, infection, poor driving, suppressed respiration, and possibly cancer. Combining these proofs with consistent evidence of association, the great weight of evidence is that hypnotics cause huge risks of decreasing a patient's duration of survival. Key PointsMost sleeping pills e.g., benzodiazepines and ''Z'' benzodiazepine agonists (like eszopiclone) are associated with early death, and they most probably cause serious increases in mortality.Benzodiazepine agonist sleeping pills and diphenhydramine should not be prescribed for insomnia, except in long-term controlled trials and hospice care.

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“…[9][10][11][12][13][14][15]33 However, concomitant opioids and sedatives have been prescribed in our clinic at a proportion (43.6%) greater than recommended by guidelines, possibly enhancing overdose risk. 10,30,34,35 We presently are modifying these regimens.…”

Section: Discussionmentioning

confidence: 99%