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Study, Mar/19: Trajectories in hypnotic use and approaching death


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Journal: Sleep Medicine


Full title: Trajectories in hypnotic use and approaching death: a register linked case-control study.






Whether the association between hypnotic and increased mortality risk is created by causation or confounding, has been long debated. We further examined the possibility of confounding by indication with a comprehensive approach.



The National FINRISK Study cohorts of 1997, 2002, and 2007 (25,436 participants aged 25-74) were followed up until July 2012. There were 1822 deaths, and at least one gender, baseline age and cohort matched 'control' was found for 1728 'cases' yielding a final analytical sample of 3955 individuals. An index age, equivalent to the age at death of their respective cases' was set for each control. Hypnotic drug purchases were followed from the Finnish nationwide register during a 36-month run-up period before the date of death/index date. The prevalence and incidence of hypnotic purchases were compared between cases and matched controls. Moreover, latent developmental trajectories of purchases were modelled and their relations with specific and all-cause death risks were analysed.



An increasing difference between cases and controls was observed as regards the use of hypnotic drugs. During the last 30 months before the date of death/index date, the rate ratio of incident purchases between cases and controls was 2.37 (95% CL, 1.79-3.12) among older and 3.61 (95% CL, 2.37-5.89) among younger individuals. The developmental trajectories of hypnotic drug purchases were differently and by interpretation plausibly associated with specific mortality risks.



In most cases the association between hypnotics and mortality risk is created by symptomatic treatment when death is approaching.




There is an accompanying editorial but it's behind a pay-wall.  It's an interesting read.  The gist is that any relationship between mortality and BZD use is confounded by indication.


Here's the link to that editorial information.  https://www.ncbi.nlm.nih.gov/pubmed/30772197

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Yeah, I think it's basically saying that the benzos aren't hastening death. They're just treating the symptoms that are common as people approach death. They do acknowledge that benzos can be problematic in the last paragraph.
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I'm not clear on this editorial.  I agree with the fact that the association is confounded by indication.  But they explain that because the mortality and use association is not disease specific and use varies based on disease trajectory, this is evidence they don't cause death?  I don't see how that conclusion necessarily follows.


Here they state:

"Neutel and Johansen showed that BZD use increases with nearness of death. Kronholm et al., showed progress in BZD use was not uniform but differed according to the course of the terminal disease from which that patient suffered. We must conclude that the association of BZD and mortality is not due to a causal relation between BZD and mortality."


I think that they would need to look at use versus no use in those with a particular disease and look how that progresses over time and compare not only mortality but time to onset of particular symptoms.


They also state:

We would agree with Kripke that BZD use should be decreased but not because the drugs themselves hasten all cause mortality or cause mortality from cancer or heart disease. BZD should be available for symptom control as appropriate, without worrying that BZD use will hasten death.


This seems a little contradictory to what they stated above?  Wording seems funny.  Maybe I'm just not following how they're explaining?

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I, too, found it hard to follow. And, of course, I disagree with the basic idea, based on what I've read and experienced. I think it's quite possible to argue this point and find studies to back up one's claim, but it's not conclusive at all. I remain skeptical.
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