65 replies to this topic

[ScienceGuy]

Prolonged usage of BENZODIAZEPINES and Z-DRUGS for the medium to long-term is ill advised due to inducing DOWN-REGULATION of the GABA RECEPTORS though GABA RECEPTOR AGONISM mechanism of action, causing TOLERANCE as well as WITHDRAWAL and REBOUND symptoms upon their cessation, as well as ADDICTION.

However, recent research now indicates that ANY usage of BENZODIAZEPINES and Z-DRUGS, even SHORT-TERM or INFREQUENT USAGE is ill advised, due to usage being associated with INCREASED MORTALITY (REDUCED LIFESPAN).

See the following study, published on 27th FEBRUARY 2012:

BMJ Open. 2012 Feb 27. doi:10.1136/bmjopen-2012-000850

Hypnotics' [Benzodiazepines’ and Z-Drugs’] association with mortality or cancer: a matched cohort study

Kripke DF, Langer RD, Kline LE
Source
¹Scripps Clinic Viterbi Family Sleep Center, La Jolla, California, USA
²Jackson Hole Center for Preventive Medicine, Jackson, Wyoming, USA

EXTRACT FROM FULL TEXT

Abstract

Objectives
An estimated 6%–10% of US adults took a hypnotic [Benzodiazepine or Z-Drug] drug for poor sleep in 2010. This study extends previous reports associating hypnotics [Benzodiazepines and Z-Drugs] with excess mortality.

Setting
A large integrated health system in the USA.

Design
Longitudinal electronic medical records were extracted for a one-to-two matched cohort survival analysis.

Subjects
Subjects (mean age 54 years) were 10 529 patients who received hypnotic [Benzodiazepine or Z-Drug] prescriptions and 23 676 matched controls with no hypnotic [Benzodiazepine or Z-Drug] prescriptions, followed for an average of 2.5 years between January 2002 and January 2007.

Main outcome measures
Data were adjusted for age, gender, smoking, body mass index, ethnicity, marital status, alcohol use and prior cancer. Hazard ratios (HRs) for death were computed from Cox proportional hazards models controlled for risk factors and using up to 116 strata, which exactly matched cases and controls by 12 classes of comorbidity.

Results
As predicted, patients prescribed any hypnotic [Benzodiazepine or Z-Drug] had substantially elevated hazards of dying compared to those prescribed no hypnotics. For groups prescribed 0.4–18, 18–132 and >132 doses/year, HRs (95% CIs) were 3.60 (2.92 to 4.44), 4.43 (3.67 to 5.36) and 5.32 (4.50 to 6.30), respectively, demonstrating a dose–response association. HRs were elevated in separate analyses for several common hypnotics, including zolpidem, temazepam, eszopiclone, zaleplon, other benzodiazepines, barbiturates and sedative antihistamines. Hypnotic [Benzodiazepine or Z-Drug] use in the upper third was associated with a significant elevation of incident cancer; HR=1.35 (95% CI 1.18 to 1.55). Results were robust within groups suffering each comorbidity, indicating that the death and cancer hazards associated with hypnotic [Benzodiazepine or Z-Drug] drugs were not attributable to pre-existing disease.

Conclusions
Receiving hypnotic [Benzodiazepine or Z-Drug] prescriptions was associated with greater than threefold increased hazards of death even when prescribed <18 pills/year. This association held in separate analyses for several commonly used hypnotics and for newer shorter-acting drugs. Control of selective prescription of hypnotics for patients in poor health did not explain the observed excess mortality.

Article summary

Article focus
Estimate the mortality risks associated with specific currently popular hypnotics in a matched cohort design, using proportional hazards regression models.

Estimate the cancer risks associated with specific currently popular hypnotics.

Explore what risk associated with hypnotics can be attributed to confounders and comorbidity.

Key messages
Patients receiving prescriptions for zolpidem, temazepam and other hypnotics [Benzodiazepines or Z-Drugs] suffered over four times the mortality as the matched hypnotic-free control patients.

Even patients prescribed fewer than 18 hypnotic [Benzodiazepine or Z-Drug] doses per year experienced increased mortality, with greater mortality associated with greater dosage prescribed.

Among patients prescribed hypnotics [Benzodiazepines or Z-Drugs], cancer incidence was increased for several specific types of cancer, with an overall cancer increase of 35% among those prescribed high doses.

Introduction
Hypnotic [Benzodiazepine or Z-Drug] drugs are among the most widely used treatments in adult medicine. We estimate that approximately 6%–10% of US adults used these drugs in 2010, and the percentages may be higher in parts of Europe. By 1979, the Cancer Prevention Study I of the American Cancer Society had found that both cigarette smoking and hypnotic [Benzodiazepine or Z-Drug] consumption were associated with excessive deaths, but the hypnotic [Benzodiazepine or Z-Drug] findings were discounted since the Cancer Prevention Study I was not designed primarily to study these drugs.

At least 24 published studies have now examined mortality associated with hypnotic [Benzodiazepine or Z-Drug] consumption (supplemental table 1). Of the 24 cited, 18 reported significant (p<0.05) associations of hypnotic [Benzodiazepine or Z-Drug] usage with increased mortality.

Lack of uniformity of measured elements makes it impossible to incorporate the majority of these studies into a meta-analysis. Nevertheless, of 22 reports from which a risk or hazard ratio (HR) for hypnotic [Benzodiazepine or Z-Drug] associated deaths could be estimated, 21 observed a risk exceeding 1.0 (p<0.001).

One study observed a RR of 1.0 associating total mortality with hypnotics but found hypnotic [Benzodiazepine or Z-Drug] use significantly associated with cancer mortality. Three other studies have reported an association of hypnotics with cancer deaths.

These studies generally failed to report the specific hypnotic [Benzodiazepine or Z-Drug] drugs used by the participants, often confounded hypnotics with tranquilisers not marketed for treatment of insomnia, and usually omitted monitoring of the quantities of hypnotic [Benzodiazepine or Z-Drug] drugs provided participants during the follow-up intervals. Moreover, previous studies had insufficient data on the short-acting benzodiazepine agonists such as zolpidem, zaleplon, and eszopiclone that now dominate the US market because their shorter duration of action is believed to provide improved safety.

Using data from longitudinal electronic medical records maintained by a large integrated US health system, the authors planned a matched cohort study to contrast mortality and cancer associations of zolpidem and other new short-acting hypnotics [Benzodiazepines and Z-Drugs] with controls and with older hypnotics.

Results
Zolpidem was the most frequently prescribed hypnotic [Benzodiazepine or Z-Drug] drug during the study interval from 2002 to 2006, and temazepam was the next most common…

Associations between hypnotic [Benzodiazepine or Z-Drug] use and death
Patients prescribed any hypnotic [Benzodiazepine or Z-Drug] had substantially elevated hazards of dying compared to those with equivalent comorbidity who took no hypnotics. Importantly, the death hazard was evident even in the lowest tertile of use…

For any hypnotic [Benzodiazepine or Z-Drug], or for zolpidem or temazepam specifically, the hazards of death in the middle tertiles of use were four to five times higher in users compared to non-users, and the hazards in the highest tertiles were five- or sixfold greater than those in non-users, indicating dose–response relationships for zolpidem and temazepam specifically and for any hypnotic [Benzodiazepine or Z-Drug].

HRs associated with levels of hypnotic consumption from Cox proportional hazards survival analyses, controlled for age, gender, ethnicity, smoking status, body mass index, marital status and alcohol use and stratified by diagnoses in 12 classes of comorbidity. N: number of patients in each dose group for deaths. Restrictions of stratification produced small differences in N for the cancer analyses. p: probability that HR=1 from Cox proportional hazards models. For each drug, the top p level is for the overall contrast among dosage categories (including the no medication or reference category), and the lower p values are for the significance of each HR referenced to no hypnotic use. HR: hazard ratio for death or cancer (95% CI). Models for zolpidem and temazepam excluded patients receiving other hypnotics. See the supplemental files for additional HRs.

The death HR associated with prescriptions for less commonly prescribed hypnotic [Benzodiazepine or Z-Drug] drugs were likewise elevated, and the confidence limits of death hazards for each other hypnotic [Benzodiazepine or Z-Drug] overlapped that for zolpidem, with the exception of eszopiclone, which was associated with higher mortality (see supplemental files).

Associations between hypnotic [Benzodiazepine or Z-Drug] use and incident major cancer
Since prior studies suggested an association between hypnotics [Benzodiazepines and Z-Drugs] and deaths from major cancers, we constructed Cox models for major cancer incidence (ie, excluding non-melanoma skin cancer incidence) and excluding all patients who had major cancers diagnosed before the period of observation. As shown in table 3, there were modestly increased statistically significant cancer HRs for those prescribed any hypnotic [Benzodiazepine or Z-Drug] compared to non-users, with the middle and highest tertiles having cancer HRs of 1.20 (95% CI 1.03 to 1.40) and 1.35 (95% CI 1.18 to 1.55), respectively. The association with zolpidem was significant for the highest tertile. The HRs for temazepam were significant for the middle tertile and the highest tertile. The cancer HR of 1.99 (95% CI 1.75 to 2.52) for the highest tertile of temazepam was significantly greater than the corresponding HRs for zolpidem or for all hypnotics combined.

Discussion
Patients with prescriptions for hypnotics [Benzodiazepines or Z-Drugs] had approximately 4.6 times the hazard of dying over an average observation period of 2.5 years as compared to non-users. These findings were robust with adjustment for multiple potential confounders and consistent using multiple strategies to address confounding by health status. A dose–response effect was seen. Among users in the highest tertiles of annualised dosages, the HRs for death were 5.3, 5.7 and 6.6, respectively, for all hypnotics [Benzodiazepines and Z-Drugs], zolpidem alone and temazepam alone. This top third of users were prescribed 92.8% of all the prescription doses of hypnotics [Benzodiazepines and Z-Drugs] (supplemental figure 2). Those in the top third were also 35% more likely to develop a new major cancer.

Perhaps the most striking finding was that an increased hazard for death was present even in the lowest tertile of hypnotic [Benzodiazepine or Z-Drug] use, such that hypnotic [Benzodiazepine or Z-Drug] drugs were associated with a 3.6-fold increased risk of dying for patients using <18 hypnotic [Benzodiazepine or Z-Drug] pills per year…

Multiple causal pathways by which hypnotics might lead to mortality have been demonstrated…

Conclusions
Rough order-of-magnitude estimates at the end of the supplemental files suggest that in 2010, hypnotics may have been associated with 320 000 to 507 000 excess deaths in the USA alone…

…the consistency of our estimates across a spectrum of health and disease suggests that the mortality effect of hypnotics [Benzodiazepines and Z-Drugs] was substantial.

Excess mortality is associated with hypnotic [Benzodiazepine or Z-Drug] use.

[hooter]

I did 8 months of 1mg clonazepam, whoops

Oh well.

[Ampa-omega]

insomnia without any help from drugs is worse. this study is a bad sign non the less.

Edited by Ampa-omega, 29 February 2012 - 10:27 PM.

[hippocampus]

same here

and I've already said: correlation is not causation. This study don't prove any direct effect, it may be just one more variable which they didn't control for. Any rodents studies at least?
I mean - lack of sleep is also associated with cancer - so it's no wonder that people who use more benzos and z-drugs have worse cancer risk ... did they control for lack of sleep in any similar study? And people with worse lifestyle tend to be more anxious and use more of these drugs ... (controlling for alcohol intake and cigarette smoking and some other variables isn't enough if you want to conclude that benzos are "guilty" for this).
Anyway, I'm surprised about very big ratios, so it may be something on it.

Edited by hippocampus, 01 March 2012 - 02:49 AM.

[ScienceGuy]

and I've already said: correlation is not causation. This study don't prove any direct effect...

I mean - lack of sleep is also associated with cancer - so it's no wonder that people who use more benzos and z-drugs have worse cancer risk ... did they control for lack of sleep in any similar study? And people with worse lifestyle tend to be more anxious and use more of these drugs ... (controlling for alcohol intake and cigarette smoking and some other variables isn't enough if you want to conclude that benzos are "guilty" for this

You need to bear in mind that this is NOT just ONE study that we are talking about here; this study is in fact simply the latest one of MANY studies indicating INCREASED MORTALITY due to BENZODIAZEPINE & Z-DRUG usage; and this study does in fact refer to such other previous studies; for example, please note the following:

"By 1979, the Cancer Prevention Study I of the American Cancer Society had found that both cigarette smoking and hypnotic [Benzodiazepine or Z-Drug] consumption were associated with excessive deaths..."

"At least 24 published studies have now examined mortality associated with hypnotic [Benzodiazepine or Z-Drug] consumption... Of the 24 cited, 18 reported significant (p<0.05) associations of hypnotic [Benzodiazepine or Z-Drug] usage with increased mortality."

"Of 22 [study] reports from which a risk or hazard ratio (HR) for hypnotic [Benzodiazepine or Z-Drug] associated deaths could be estimated, 21 observed a risk..."

"One study [which specifically reviewed cancer mortality as part of the study] found hypnotic [Benzodiazepine or Z-Drug] use significantly associated with cancer mortality..."

"Three other studies have [included reviewing cancer mortality as part of the study and] reported an association of hypnotics with cancer deaths."

"Multiple causal pathways by which hypnotics might lead to mortality have been demonstrated."

You are absolutely correct that ASSOCIATION does not always equal CAUSALITY; however, when all the existing evidence, including both this latest study, and all previous studies and/or research are taken into consideration there does in fact appear to be conclusive substantiated evidence supporting the fact that BENZODIAZEPINE & Z-DRUG use does indeed cause INCREASED MORTALITY

Edited by ScienceGuy, 01 March 2012 - 08:08 AM.

[ScienceGuy]

insomnia without any help from drugs is worse. this study is a bad sign non the less.

Please kindly note that for INSOMNIA SUFFERERS it is NOT a case of choosing between BENZODIAZEPINE & Z-DRUG USAGE and INSOMNIA, in that fortunately there are many other alternative effective treatments for INSOMNIA, which unlike BENZODIAZEPINES & Z-DRUGS are in fact also safe

Furthermore, prolonged usage of BENZODIAZEPINES and Z-DRUGS for the medium to long-term is ill advised due to inducing DOWN-REGULATION of the GABA RECEPTORS though GABA RECEPTOR AGONISM mechanism of action, causing TOLERANCE as well as WITHDRAWAL and REBOUND symptoms upon their cessation, as well as ADDICTION. Therefore, where the INSOMNIA is a MEDICAL CONDITION that requires prolonged treatment for the medium to long-term, usage of BENZODIAZEPINES and Z-DRUGS is ill advised anyway

Edited by ScienceGuy, 01 March 2012 - 08:19 AM.

[hippocampus]

do you have any data speciffically about alprazolam?

[ScienceGuy]

Hi everyone,

Please kindly note that for a variety of reasons I will now be taking a break from this forum for a while.

I'd like to say a huge THANK YOU to everyone who has contributed POSITIVELY to my various threads and this forum in general.

I will most certainly endeavour to revisit this forum and takes matters forward if or when I return.

In the interim I wish you all the very best; and for the time being this is ScienceGuy signing out.

[medievil]

Pretty flawed study

[wowser]

Pretty flawed study

lol! which one? you clearly epic failed to read this:

You need to bear in mind that this is NOT just ONE study that we are talking about here; this study is in fact simply the latest one of MANY studies indicating INCREASED MORTALITY due to BENZODIAZEPINE & Z-DRUG usage; and this study does in fact refer to such other previous studies; for example, please note the following:

"By 1979, the Cancer Prevention Study I of the American Cancer Society had found that both cigarette smoking and hypnotic [Benzodiazepine or Z-Drug] consumption were associated with excessive deaths..."

"At least 24 published studies have now examined mortality associated with hypnotic [Benzodiazepine or Z-Drug] consumption... Of the 24 cited, 18 reported significant (p<0.05) associations of hypnotic [Benzodiazepine or Z-Drug] usage with increased mortality."

"Of 22 [study] reports from which a risk or hazard ratio (HR) for hypnotic [Benzodiazepine or Z-Drug] associated deaths could be estimated, 21 observed a risk..."

"One study [which specifically reviewed cancer mortality as part of the study] found hypnotic [Benzodiazepine or Z-Drug] use significantly associated with cancer mortality..."

"Three other studies have [included reviewing cancer mortality as part of the study and] reported an association of hypnotics with cancer deaths."

"Multiple causal pathways by which hypnotics might lead to mortality have been demonstrated."

You are absolutely correct that ASSOCIATION does not always equal CAUSALITY; however, when all the existing evidence, including both this latest study, and all previous studies and/or research are taken into consideration there does in fact appear to be conclusive substantiated evidence supporting the fact that BENZODIAZEPINE & Z-DRUG use does indeed cause INCREASED MORTALITY

[medievil]

Pretty flawed study

lol! which one? you clearly epic failed to read this:

You need to bear in mind that this is NOT just ONE study that we are talking about here; this study is in fact simply the latest one of MANY studies indicating INCREASED MORTALITY due to BENZODIAZEPINE & Z-DRUG usage; and this study does in fact refer to such other previous studies; for example, please note the following:

"By 1979, the Cancer Prevention Study I of the American Cancer Society had found that both cigarette smoking and hypnotic [Benzodiazepine or Z-Drug] consumption were associated with excessive deaths..."

"At least 24 published studies have now examined mortality associated with hypnotic [Benzodiazepine or Z-Drug] consumption... Of the 24 cited, 18 reported significant (p<0.05) associations of hypnotic [Benzodiazepine or Z-Drug] usage with increased mortality."

"Of 22 [study] reports from which a risk or hazard ratio (HR) for hypnotic [Benzodiazepine or Z-Drug] associated deaths could be estimated, 21 observed a risk..."

"One study [which specifically reviewed cancer mortality as part of the study] found hypnotic [Benzodiazepine or Z-Drug] use significantly associated with cancer mortality..."

"Three other studies have [included reviewing cancer mortality as part of the study and] reported an association of hypnotics with cancer deaths."

"Multiple causal pathways by which hypnotics might lead to mortality have been demonstrated."

You are absolutely correct that ASSOCIATION does not always equal CAUSALITY; however, when all the existing evidence, including both this latest study, and all previous studies and/or research are taken into consideration there does in fact appear to be conclusive substantiated evidence supporting the fact that BENZODIAZEPINE & Z-DRUG use does indeed cause INCREASED MORTALITY

Ppl using benzo's are usually in worse health

[wowser]

Pretty flawed study

lol! which one? you clearly epic failed to read this:

You need to bear in mind that this is NOT just ONE study that we are talking about here; this study is in fact simply the latest one of MANY studies indicating INCREASED MORTALITY due to BENZODIAZEPINE & Z-DRUG usage; and this study does in fact refer to such other previous studies; for example, please note the following:

"By 1979, the Cancer Prevention Study I of the American Cancer Society had found that both cigarette smoking and hypnotic [Benzodiazepine or Z-Drug] consumption were associated with excessive deaths..."

"At least 24 published studies have now examined mortality associated with hypnotic [Benzodiazepine or Z-Drug] consumption... Of the 24 cited, 18 reported significant (p<0.05) associations of hypnotic [Benzodiazepine or Z-Drug] usage with increased mortality."

"Of 22 [study] reports from which a risk or hazard ratio (HR) for hypnotic [Benzodiazepine or Z-Drug] associated deaths could be estimated, 21 observed a risk..."

"One study [which specifically reviewed cancer mortality as part of the study] found hypnotic [Benzodiazepine or Z-Drug] use significantly associated with cancer mortality..."

"Three other studies have [included reviewing cancer mortality as part of the study and] reported an association of hypnotics with cancer deaths."

"Multiple causal pathways by which hypnotics might lead to mortality have been demonstrated."

You are absolutely correct that ASSOCIATION does not always equal CAUSALITY; however, when all the existing evidence, including both this latest study, and all previous studies and/or research are taken into consideration there does in fact appear to be conclusive substantiated evidence supporting the fact that BENZODIAZEPINE & Z-DRUG use does indeed cause INCREASED MORTALITY

Ppl using benzo's are usually in worse health

you need glasses mate... because u clearly cant read! lol! it makes perfectly clear that these studies eliminated the influencing factor of comorbidity through controls and otherwise... so, despite ur statement being a gross overgeneralisation, it is actually irrelevant and not applicable... are u deliberately being obtuse or what? or are u such a huge fan of benzos despite the fact its proven they kill people that youve got ur head stuck so far up ur arse that u cant see the wood for trees?

imo benzos and z-drugs should be banned! medicine has advanced alot more now and theres much better and safer alternatives including better medical drugs now for treating anxiety and insomnia that dont kill you or make u want to kill yourself!

[hooter]

you need glasses mate... because u clearly cant read! lol! it makes perfectly clear that these studies eliminated the influencing factor of comorbidity through controls and otherwise... so, despite ur statement being a gross overgeneralisation, it is actually irrelevant and not applicable... are u deliberately being obtuse or what? or are u such a huge fan of benzos despite the fact its proven they kill people that youve got ur head stuck so far up ur arse that u cant see the wood for trees?

imo benzos and z-drugs should be banned! medicine has advanced alot more now and theres much better and safer alternatives including better medical drugs now for treating anxiety and insomnia that dont kill you or make u want to kill yourself!

Hope you feel like a real hardened internet toughguy after personally insulting a schizophrenic user instead of politely showing he's wrong.

[wowser]

you need glasses mate... because u clearly cant read! lol! it makes perfectly clear that these studies eliminated the influencing factor of comorbidity through controls and otherwise... so, despite ur statement being a gross overgeneralisation, it is actually irrelevant and not applicable... are u deliberately being obtuse or what? or are u such a huge fan of benzos despite the fact its proven they kill people that youve got ur head stuck so far up ur arse that u cant see the wood for trees?

imo benzos and z-drugs should be banned! medicine has advanced alot more now and theres much better and safer alternatives including better medical drugs now for treating anxiety and insomnia that dont kill you or make u want to kill yourself!

Hope you feel like a real hardened internet toughguy after personally insulting a schizophrenic user instead of politely showing he's wrong.

sorry if i came across a bit harsh... im probably overly sensitive about this subject cos my sister recently tried to kill herself and benzos had a lot to do with it... both why and how... and it annoyed me that this guy seems to think benzos and z-drugs are the best thing since sliced bread despite all the proof that they are the spawn of the devil and should be banned! i think i need to increase my piracetam dosage or something so these things dont irritate me so much! lol!

[medievil]

My reply was oversimplified; i remember a post elaborating more about the flaws in that study.

Besides that there are no alternatives for benzo's that are as effective; banning them leaves many ppl with untreated issues.

[medievil]

you need glasses mate... because u clearly cant read! lol! it makes perfectly clear that these studies eliminated the influencing factor of comorbidity through controls and otherwise... so, despite ur statement being a gross overgeneralisation, it is actually irrelevant and not applicable... are u deliberately being obtuse or what? or are u such a huge fan of benzos despite the fact its proven they kill people that youve got ur head stuck so far up ur arse that u cant see the wood for trees?

imo benzos and z-drugs should be banned! medicine has advanced alot more now and theres much better and safer alternatives including better medical drugs now for treating anxiety and insomnia that dont kill you or make u want to kill yourself!

Hope you feel like a real hardened internet toughguy after personally insulting a schizophrenic user instead of politely showing he's wrong.

sorry if i came across a bit harsh... im probably overly sensitive about this subject cos my sister recently tried to kill herself and benzos had a lot to do with it... both why and how... and it annoyed me that this guy seems to think benzos and z-drugs are the best thing since sliced bread despite all the proof that they are the spawn of the devil and should be banned! i think i need to increase my piracetam dosage or something so these things dont irritate me so much! lol!

Best thing since sliced bread? I just think they are currently still needed for many individuals thats all.

[medievil]

"Zopiclone may be carcinogenic and mutagenic according to rat, mice and hamster studies. It should be noted that, at 100 mg per kg of bodyweight per day, the dosage was considerably higher than the therapeutic dose for humans. The authors of an uncontrolled study of Zopiclone said that it may take decades in immunocompetent people before carcinogenic effects from past zopiclone use develops. It was suggested that further research and monitoring was required into the potential for zopiclone to cause cancer in immunocompetant patients.[1]

A recent analysis of FDA and clinical trial data shows that nonbenzodiazepine Z-drugs at prescribed doses cause cancer in humans. The data shows that trial subjects receiving hypnotic drugs had an increased the risk of developing cancer and malignancies. There have been 15 epidemiologic studies which have shown that hypnotic drugs cause increased mortality, mainly due to increased cancer deaths. The cancers included, cancer of the brain, lung, bowel, breast, and bladder, and neoplasms. Initially FDA reviewers did not want to approve the drugs due to concerns of cancer but ultimately changed their mind and approved the drugs despite the concerns. FDA data has shown that zolpidem, zaleplon and eszopiclone are clastogenic and cause cancer in rodents. Benzodiazepine agonists are associated with an increased risk of ovarian cancer in humans. Zopiclone was reportedly refused a product license by the FDA in the USA due to indications that zopiclone caused cancer. Development of a malignant neoplasm has been associated with zolpidem usage but the rate of incidence of neoplasm in zolpidem users is as yet unknown. The rates, in clinical trials for the nonbenzodiazepine Z drugs, of malignancies and neoplasms are significantly higher in hypnotic groups than in placebo groups. Also the analysis of clinical trials and FDA data showed that eszopiclone, zaleplon, and zolpidem appeared to have an adverse effect on the immune system causing an increased rate of infections and colds in hypnotic users. Suppression of immune function might be the cause of the increased rate of cancer in nonbenzodiazepine hypnotic users. Indiplon has also shown an increased rate of cancers in clinical trials. The review author concluded saying; "the likelihood of cancer causation is sufficiently strong now that physicians and patients should be warned that hypnotics possibly place patients at higher risk for cancer".[2]"

Most ppl inthis study took the z drug ambien; argument 1 against this study; this shouldnt be generalised to normal benzo's

ill post more later

[medievil]

Pretty flawed study

lol! which one? you clearly epic failed to read this:

You need to bear in mind that this is NOT just ONE study that we are talking about here; this study is in fact simply the latest one of MANY studies indicating INCREASED MORTALITY due to BENZODIAZEPINE & Z-DRUG usage; and this study does in fact refer to such other previous studies; for example, please note the following:

"By 1979, the Cancer Prevention Study I of the American Cancer Society had found that both cigarette smoking and hypnotic [Benzodiazepine or Z-Drug] consumption were associated with excessive deaths..."

"At least 24 published studies have now examined mortality associated with hypnotic [Benzodiazepine or Z-Drug] consumption... Of the 24 cited, 18 reported significant (p<0.05) associations of hypnotic [Benzodiazepine or Z-Drug] usage with increased mortality."

"Of 22 [study] reports from which a risk or hazard ratio (HR) for hypnotic [Benzodiazepine or Z-Drug] associated deaths could be estimated, 21 observed a risk..."

"One study [which specifically reviewed cancer mortality as part of the study] found hypnotic [Benzodiazepine or Z-Drug] use significantly associated with cancer mortality..."

"Three other studies have [included reviewing cancer mortality as part of the study and] reported an association of hypnotics with cancer deaths."

"Multiple causal pathways by which hypnotics might lead to mortality have been demonstrated."

You are absolutely correct that ASSOCIATION does not always equal CAUSALITY; however, when all the existing evidence, including both this latest study, and all previous studies and/or research are taken into consideration there does in fact appear to be conclusive substantiated evidence supporting the fact that BENZODIAZEPINE & Z-DRUG use does indeed cause INCREASED MORTALITY

Ppl using benzo's are usually in worse health

Elaboratio

Comorbidity of insomnia and depression.

Staner L.

Source

Sleep Laboratory, Forenap, Centre Hospitalier de Rouffach, 27 rue du 4ème R.S.M. F-68250 Rouffach, France. luc.staner@forenap.com

Abstract

During the last decade, several studies have shown that insomnia, rather than a symptom of depression, could be a medical condition on its own, showing high comorbidity with depression. Epidemiological research indicates that insomnia could lead to depression and/or that common causalities underlie the two disorders. Neurobiological and sleep EEG studies suggest that a heightened level of arousal may play a common role in both conditions and that signs of REM sleep disinhibition may appear in individuals prone to depression. The effects of antidepressant drugs on non-REM and REM sleep are discussed in relation to their use in insomnia comorbid with depression. Empirical treatment approaches are behavioral management of sleep combined with prescription of a sedative antidepressant alone, co-prescription of two antidepressants, or of an antidepressant with a hypnotic drug.

Insomnia in Selected Anxiety Disorders

The anxiety disorders include generalized anxiety disorder, panic disorder, PTSD, obsessive compulsive disorder, and phobic disorders. Their central feature is anxiety, which is persistent, maladaptively triggered, and of sufficient intensity to disrupt function. Insomnia, as a symptom, is a core feature of both PTSD and generalized anxiety disorder (GAD). It is also commonly seen in panic disorder. The most commonly represented group of disorders in populations of people with insomnia is the group of anxiety disorders.

^[1]

Background: Depressive and anxiety disorders
commonly occur together

http://www.psycard.com/down/gbjl01.pdf

Excess mortality in depression: a meta-analysis of community studies.

Cuijpers P, Smit F.

Source

Netherlands Institute of Mental Health and Addiction, Trimbos Institute, PO Box 725, 3500 AS, Utrecht, The Netherlands. pcuijpers@trimbos.nl

Abstract

BACKGROUND:

Although most studies examining the relationship between depression and mortality indicate that there is excess mortality in depressed subjects, this is not confirmed in all studies. Furthermore, it has been hypothesized that mortality rates in depressed men are higher than in depressed women. Finally, it is not clear if the increased mortality rates exist only in major depression or also in subclinical depression.
METHODS:

A meta-analysis was conducted to examine these questions. A total of 25 studies with 106,628 subjects, of whom 6416 were depressed, were examined. Both univariate and multivariate analyses were conducted.
RESULTS:

The overall relative risk (RR) of dying in depressed subjects was 1.81 (95% CI: 1.58-2.07) compared to non-depressed subjects. No major differences were found between men and women, although the RR was somewhat larger in men. The RR in subclinical depression was no smaller than the RR in clinical depression.
LIMITATIONS:

Only RRs of mortality were examined, which were not corrected for important confounding variables, such as chronic illnesses, or life-style. In the selected studies important differences existed between study characteristics and populations. The number of comparisons was relatively small.
CONCLUSIONS:

There is an increased risk of mortality in depression. An important finding of this study is that the increased risk not only exists in major depression, but also in subclinical forms of depression. In many cases, depression should be considered as a life-threatening disorder.

Im sure you guys ca

n i

nterpret this correctly.

Benzo's are used for insomnia and anxiety wich in many cases are comorbid with depression; and depression causes excessive mortality.

Please show some skeptism with this kind of study's instead of taking it as ultimate proof; while there may be some truth to it; this study has major flaws

Edited by medievil, 11 March 2012 - 11:55 AM.

[hooter]

My reply was oversimplified; i remember a post elaborating more about the flaws in that study.

Besides that there are no alternatives for benzo's that are as effective; banning them leaves many ppl with untreated issues.

Ok now you're actually being a piece of shit.

[wowser]

Im sure you guys ca

n i

nterpret this correctly.

Benzo's are used for insomnia and anxiety wich in many cases are comorbid with depression; and depression causes excessive mortality.

Please show some skeptism with this kind of study's instead of taking it as ultimate proof; while there may be some truth to it; this study has major flaws

theres a couple of huge gaping holes in ur argument:

1 - you keep referring to "this study" when in fact we are talking about dozens and dozens of studies all of which show increased mortality with use of benzos and z-drugs... i already corrected u regarding this but this seems to keep falling on deaf ears... lol!

2 - as i have already pointed out to you it makes perfectly clear that these studies eliminated the influencing factor of comorbidity through controls and otherwise... so ur so called flaws dont exist... lol!

3 - there are also dozens and dozens of studies showing many other reasons why taking benzos and z-drugs is a really bad idea... they cause depression, suicide and other psycological problems for starters... so ur simply replacing one problem with others caused by the benzo or z-drug

[medievil]

My reply was oversimplified; i remember a post elaborating more about the flaws in that study.

Besides that there are no alternatives for benzo's that are as effective; banning them leaves many ppl with untreated issues.

Ok now you're actually being a piece of shit.

Why then?

[wowser]

My reply was oversimplified; i remember a post elaborating more about the flaws in that study.

Besides that there are no alternatives for benzo's that are as effective; banning them leaves many ppl with untreated issues.

Ok now you're actually being a piece of shit.

im totally agreeing this hooter... ur being deliberately obtuse and talking out ur arse... i suggest u need to admit urself into clinic for psycological medical treatment immediately... hope u and ur benzos are very happy together... for ur limited lifespan due to being killed by them that is! lol!

[medievil]

Im sure you guys ca

n i

nterpret this correctly.

Benzo's are used for insomnia and anxiety wich in many cases are comorbid with depression; and depression causes excessive mortality.

Please show some skeptism with this kind of study's instead of taking it as ultimate proof; while there may be some truth to it; this study has major flaws

theres a couple of huge gaping holes in ur argument:

1 - you keep referring to "this study" when in fact we are talking about dozens and dozens of studies all of which show increased mortality with use of benzos and z-drugs... i already corrected u regarding this but this seems to keep falling on deaf ears... lol!

2 - as i have already pointed out to you it makes perfectly clear that these studies eliminated the influencing factor of comorbidity through controls and otherwise... so ur so called flaws dont exist... lol!

3 - there are also dozens and dozens of studies showing many other reasons why taking benzos and z-drugs is a really bad idea... they cause depression, suicide and other psycological problems for starters... so ur simply replacing one problem with others caused by the benzo or z-drug

If you did im srry; i sometimes read over stuff with my ADHD; ill look into those study's.

For point 2 i didnt read that in the article ive read about this study; i will recheck this again.

For the last point; take in mind that while they are able to cause depression; a ton of are def helped by them; dont ignore this.

[medievil]

My reply was oversimplified; i remember a post elaborating more about the flaws in that study.

Besides that there are no alternatives for benzo's that are as effective; banning them leaves many ppl with untreated issues.

Ok now you're actually being a piece of shit.

im totally agreeing this hooter... ur being deliberately obtuse and talking out ur arse... i suggest u need to admit urself into clinic for psycological medical treatment immediately... hope u and ur benzos are very happy together... for ur limited lifespan due to being killed by them that is! lol!

Wow wtf! all i did was use arguments against this study; and im open to counterarguments and will accept the facts; besides that i only use benzo's till i have lmethylfolate; im not really a fan of them tbh just atm helps ritalin anxiety; you arent being very nice when i just wanted to discuss this study

[medievil]

Again from what im reading they controlled for poor health and not for comorbid depression; but please correct me if im wrong.

[wowser]

My reply was oversimplified; i remember a post elaborating more about the flaws in that study.

Besides that there are no alternatives for benzo's that are as effective; banning them leaves many ppl with untreated issues.

Ok now you're actually being a piece of shit.

im totally agreeing this hooter... ur being deliberately obtuse and talking out ur arse... i suggest u need to admit urself into clinic for psycological medical treatment immediately... hope u and ur benzos are very happy together... for ur limited lifespan due to being killed by them that is! lol!

Wow wtf! all i did was use arguments against this study; and im open to counterarguments and will accept the facts; besides that i only use benzo's till i have lmethylfolate; im not really a fan of them tbh just atm helps ritalin anxiety; you arent being very nice when i just wanted to discuss this study

well u arent being very nice either by making light of just how freakin' dangerous benzos and z-drugs actually are! and thanks for confirming u take benzos urself... i had guessed as much! ur in denial mate... the sooner u wake up and see the wood for trees about how bad these things are for u the better for u!

for the record my sister is lucky to still be alive after taking benzos... they made her suicidal and she tried to kill herself! also a friend of mine whose been fit as a fiddle all his life, doesnt smoke or drink and is practically ocd bout eating healthy, was diagnosed with cancer after being on benzos for 2 years... makes perfect sense now having found out about all these studies... just sayin

[medievil]

I just posted my opinion and my arguments; there's nothing not nice about that; i never insulted anyone here.




I only take diazepam because i ran out of lmethylfolate;but again i need to do more research to make come conclusions about this as to me it still seems they controlled for health issues and not depression but i may be wrong; i also havent looked into the other study's yet.

The big issue here is that for some people they are the only solution for insomnia or anxiety; there are alternatives but those dont work for everyone; or what is your opinion on this?


Benzo's also gave many with SA a life; doesnt that count? i do however agree that the risk should be warned about.

[hooter]

I just posted my opinion and my arguments; there's nothing not nice about that; i never insulted anyone here.

You didn't say it was your opinion. You stated it as if it were a fact. Not only that but you posted like 4-5 posts in a row with quotes, this is really tiresome to dig through for anyone reading the thread.

Benzo's also gave many with SA a life; doesnt that count? i do however agree that the risk should be warned about.

Once these people get off benzos, they either get permanently worse than they've ever been in their lives or even possibly die. I don't think some temporary anxiolysis counts when you consider the considerable brain damage that goes along with it.

Edited by hooter, 11 March 2012 - 12:48 PM.

[medievil]

I agree that the protracted withdrawals are horrid; i

never said i love them; but i do think some ppl benefit of them long term. They do cause cognitive decline over time wich is bad.

Also i looked benzodiazepine mortality on pubmed and after this study; the next one i found is this one

Mortality associated with benzodiazepines and benzodiazepine-related drugs among community-dwelling older people in Finland: a population-based retrospective cohort study.

Gisev N, Hartikainen S, Chen TF, Korhonen M, Bell JS.

Source

Faculty of Pharmacy, The University of Sydney, New South Wales, Australia. natasa.gisev@sydney.edu.au

Abstract

OBJECTIVE:

To investigate the association between the use of benzodiazepines (BDZs) and BDZ-related drugs and mortality among community-dwelling people aged 65 years and older in Finland.
METHOD:

This was a population-based retrospective cohort study. Records of all reimbursed drugs purchased by all 2224 residents of Leppävirta, Finland, aged 65 years and older in 2000 were extracted from the Finnish National Prescription Register. Diagnostic data were extracted from the Special Reimbursement Register. All-cause mortality was assessed after 9 years using national registers. Cox proportional hazards models were used to compute unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals for mortality among prevalent users of BDZs and BDZ-related drugs in 2000 (n = 325), compared with nonusers of BDZs and BDZ-related drugs between 2000 and 2008 (n = 1520).
RESULTS:

BDZs and BDZ-related drugs were used by 325 out of the 2224 residents (14.6%) in 2000. The 9-year mortality was 50.2% among BDZ and BDZ-related drug users in 2000 and 36.3% among BDZ and BDZ-related drug nonusers between 2000 and 2008 (HR 1.53; 95% CI 1.28 to 1.82). After adjusting for baseline age, sex, antipsychotic drug use, and diagnostic confounders, the HR was 1.01 (95% CI 0.84 to 1.21).
CONCLUSIONS:

Use of BDZs and BDZ-related drugs was associated with an increased

mortality

hazard in unadjusted analyses. However, after adjusting for age, sex, antipsychotic drug use, and diagnostic confounders, the use of BDZs and BDZ-related drugs was not associated with excess

mortality

.

Please point me to all those other study's showing increased mortality; and i would like a full text confirming they controlled for depression and not just poor health

Edited by medievil, 11 March 2012 - 01:23 PM.