Study, May/20: Effects of Chronic Benzodiazepine Use in Depression...

The full title of this Canadian study is "Understanding the Effects of Chronic Benzodiazepine Use in Depression: A Focus on Neuropharmacology ".

 

Note: I tried unsuccessfully to find the full study for this one, since the topic is likely of interest to many around here. If anyone is able to track it down, please share it! Thanks.

 

https://pubmed.ncbi.nlm.nih.gov/32459725/

 

 

Abstract

 

Benzodiazepines are frequently prescribed on an ongoing basis to individuals with depression, mainly to alleviate anxiety or insomnia, despite current guideline recommendations that continuous use should not exceed 4 weeks. Currently, there are no efficacy trials published beyond 8 weeks. Several antidepressant trials demonstrate that the concomitant use of a benzodiazepine is associated with poorer depressive outcomes and functional status; however, it is unclear why this is the case. Patients with depression receiving a benzodiazepine may reflect a more ill or high anxiety group, although even within anxiety disorders, the use of a benzodiazepine is associated with poorer outcomes. The neuroadaptive consequences of long-term benzodiazepine use may be a factor underlying these findings. Chronic benzodiazepine use results in decreased gamma-aminobutyric acid and monoaminergic function, as well as interference with neurogenesis, which are all purported to play a role in antidepressant efficacy. This review will discuss the oppositional neuropharmacological interactions between chronic benzodiazepine use and antidepressant mechanism of action, which could result in reduced antidepressant efficacy and function in depression.

Yet another great find and share, Lapis2.  Thank you!

 

I’ve looked for the full paper as well with no success.  Let’s hope another member can find it.  The following quote from the abstract is intriguing:

 

“The neuroadaptive consequences of long-term benzodiazepine use may be a factor underlying these findings. Chronic benzodiazepine use results in decreased gamma-aminobutyric acid and monoaminergic function, as well as interference with neurogenesis ...”

 

 

You're welcome, Libertas! Yes, definitely intriguing. I should have shared the definition of "monoaminergic" too.

 

Here it is, from Wikipedia:

 

Monoaminergic means "working on monoamine neurotransmitters", which include serotonin, dopamine, norepinephrine, epinephrine, and histamine.

 

A monoaminergic, or monoaminergic drug, is a chemical which functions to directly modulate the serotonin, dopamine, norepinephrine, epinephrine, and/or histamine neurotransmitter systems in the brain. Monoaminergics include catecholaminergics (which can be further divided into adrenergics and dopaminergics), serotonergics, and histaminergics. An example of a class of monoaminergic drugs is monoamine oxidase inhibitors (MAOIs).

 

https://en.wikipedia.org/wiki/Monoaminergic

 

 

Is “mind-reader” on your long list of talents, Lapis2? How did you know that my next action item was to look up the definition of “monoaminergic”?

Is “mind-reader” on your long list of talents, Lapis2? How did you know that my next action item was to look up the definition of “monoaminergic”?

 

Well, my dear Libertas, I would say that you and I are the curious type and, as they say, "Curious minds wanna know!"

 

Do "they" say that?! I can't remember if they do, but someone says that.

Is “mind-reader” on your long list of talents, Lapis2? How did you know that my next action item was to look up the definition of “monoaminergic”?

 

Well, my dear Libertas, I would say that you and I are the curious type and, as they say, "Curious minds wanna know!"

 

Do "they" say that?! I can't remember if they do, but someone says that.

 

Well, I went looking for more info and found this:

 

https://www.quora.com/Where-did-the-phrase-inquiring-minds-want-to-know-come-from

 

;D

I agree with you, Lapis2 — you and I are indeed the curious type. I too searched for the origins of the phrase “Inquiring minds want to know.” after your last post.   Libertas

I agree with you, Lapis2 — you and I are indeed the curious type. I too searched for the origins of the phrase “Inquiring minds want to know.” after your last post.   Libertas

 

Well, according to that quora thing I found, it should read "Enquiring minds want to know", which comes from an ad for the National Enquirer. 

I finally found the full study for this one here on SciHub:

 

https://sci-hub.tw/https://www.researchgate.net/publication/341688809_Understanding_the_effects_of_chronic_benzodiazepine_use_in_depression_a_focus_on_neuropharmacology

 

I'm just reading it now, and I do think others would be very interested in it as well. There's excellent information on long-term benzodiazepine use. Check out Figure 1 and Table 1.

 

Introduction

 

Benzodiazepines  are  sedative  anxiolytics  that  are  prescribed  for  the  treatment  of  anxiety,  insomnia,  pain,  or  as  anesthetic  or  anticonvulsant  agents.  Prescribing  benzodiazepines  for  chronic  use  is  not  recommended  due  to  their  addictive  potential,  negative  cognitive  effects,  increased  risk  of  dementia  and  injurious  falls,  and  lack  of demonstrated efficacy beyond 4 weeks in prospective trials (Lader, 2011; Federico et al., 2017; Islam et al., 2016; Picton et  al.,  2018;  He  et  al.,  2019).  Importantly,  in  the  treatment of major depressive disorder (MDD), there is a consensus among international guidelines that there is a limited role for benzodiazepines. Prominent guidelines caution  against  long-term  benzodiazepine  use,  and  recommend  that  benzodiazepines  only  be  used  short-term  (~4  weeks)  with  an  antidepressant  if  symptoms  of  anxiety,  insomnia,  or  agitation  are  present  (Davidson,  2010;  Higuchi, 2010; Kennedy et al., 2016). Nonetheless, long-term  benzodiazepine  prescription  accounts  for  up  to  one-third  of  all  benzodiazepine  prescriptions  for  elderly  individuals  (Zhang,  2010;  Lai  et  al.,  2011;  Olfson  et  al., 2015; Bushnell et al., 2017; Zhong et al., 2019), and have increased over time (Kaufmann et al., 2018).

 

Data  from  the  Canadian  National  Population  Health  Survey revealed that 2–3% of individuals in the general community  are  receiving  benzodiazepine  (Patten  et  al., of whom 80% received prescriptions for more than 1 year  (Esposito et al., 2009). In Canada and Brazil, among those  who  have  had  a  major  depressive  episode  in  the  last 12 months, 50% are prescribed concomitant benzodiazepine therapy (Sanyal et al., 2011; Fulone et al., 2018). Estimates from European countries reveal 14–16% of the adult population reported receiving at least one benzodiazepine  prescription  annually,  with  the  majority  considered  to  be  long-term  users  (Petitjean  et  al.,  2007;  Cloos  et al., 2015). In the USA, the number of benzodiazepine prescriptions has increased three or more fold in the past decade,  driven  mainly  by  long-term  users  (Bachhuber  et  al.,  2016;  Agarwal  and  Landon,  2019;  Johansen  and  Niforatos, 2019). Predictors of long-term benzodiazepine use  include  older  age,  female  sex,  presence  of  MDD  or  an  anxiety  disorder,  antidepressant  initiation  and  pain  (Liu et al., 2010; Patten et al., 2010; Manthey et al., 2011; Préville et al., 2011; Hawkins et al., 2012; ).

 

Given  that  benzodiazepines  and  antidepressants  are  frequently  co-prescribed,  it  is  important  to  evaluate  the  potential pharmacologic interactions of benzodiazepines with common antidepressants prescribed for depression; especially considering evidence that long-term benzodiazepine use is associated with treatment resistance (Rizvi et  al.,  2014;  Parker  and  Graham,  2015).  The  aim  of  this  narrative  review  is  to  elucidate  the  potential  interaction  of  long-term  benzodiazepine  use  with  antidepressant  treatment outcomes, the neuropharmacological and neurobiological  effects  of  long-term  benzodiazepine  use,  efficacy,  and  the  clinical  implications  of  continued  benzodiazepine use.

And now it looks like that SciHub link to the full study is no longer working. Very frustrating. It was a really interesting study. If anyone does, indeed, have access to a medical library and can track this one down, it would be great if they could share it here.