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#+AUTHOR: Armin Moradi
#+TITLE: Benzos in the elderly
#+DATE: 2021-11-12
* Hi there!
Benzos in elderly
#+begin_notes
Welcome to today's QI rounds. Thank you for joining. Today I'll be talking about prescribing benzodiazepines in the elderly as an overarching theme. We'll go over a case study which happens to be a more typical scenario than we'd like to see, point out the odd sights in the medication record, and discuss benzodiazepines as a class of drugs. Hopefully this lecture will make everyone more equipped to deal with cases similar to our scenario here.
Please note that the name and age has been anonymized for this case study.
#+end_notes
* Becky
#+begin_notes
So we have Becky 75yo lady who presented to hospital meeting criteria for MDD with fleeting passive SI. Stressors included covid isolation, recent lymphoma dx, recent passing of brother and sister due to covid complications. She met criteria for MDD, and reported that although she wasn't worried about anything, she "physically" felt anxious. She reported feeling tense, keyed up, and feeling like something bad is going to happen. She was diagnosed with MDD with anxious distress, and admitted.
#+end_notes
* The Past
- Family Physician
- Depression
- Venlafaxine
* Med Trail
- Venlafaxine
- Fluoxetine
- Paroxetine
- Bupropion
- Sertraline
#+begin_notes
She has been suffering from depressive symptoms for some time, so she was trialed by her family physician in the community on venlafaxine for 2 weeks, fluoxetine for 1 week, and paroxetine for 1 week and deemed that none of them were effective. She was also trialed on Bupropion which worsened her anxiety symptoms. Lastly, she was started on Sertraline titrated to 75mg by 25mg/week which improved her depressive symptoms but worsened anxiety.
#+end_notes
* Med Trail 2.0
- Alprazolam 0.5 bid
- Then tid
#+begin_notes
Somewhere along the way, she was started on Alprazolam 0.5mg bid. She has reportedly been on it for more than a year, so we can presume the anxiety symptoms have been present for at least that long and gotten unmanageable by then.
Around the time her sertraline was being titrated and was at 75mg, she presented to hospital with worsening anxiety. She was discharged home with reduction in sertraline to 50 and increasing alprazolam to 0.5 tid.
Note that I'm intentionally presenting the case vaguely. I don't intend to focus on this case as an isolated event and so I'm doing a lot of hand-wavy descriptions of what happened with loose timelines. My intention to consider this scenario as something that can generalized to a fair number of cases we see regarding how benzos are used, and be alert to when and how we can intervene.
With that said, that's pretty much the end of the case presentation. Let's discuss the key points and a bit of background that helps us better analyze this scenario.
#+end_notes
* Benzo
- short
- medium
- long
#+begin_notes
Benzodiazepines are a class of drugs that act on the benzodiazepine receptors at the GABA-A ligand gated chloride channels and allows more chloride to rush through, enhancing GABA activity, which is inhibitory. Presumably work in amygdala fear circuits. That's how it's beneficial in treatment of anxiety.
It's a good short term solution, however, it has unfortunate side effects. Before we get into that, let's talk about the benzos themselves.
#+end_notes
* Benzo - short
Midaz and Triaz
#+begin_notes
The two truly short acting benzos are midazolam and triazolam. Midazolam has a half life of 1.5-2.5 hours and acts within 5 minutes IV, 15min IM, and 20min PO. Triazolam is similar, acting within 20min PO with a half life between 1.5-5.5 hours. I haven't seen triazolam used here, but midazolam is sometimes used in ER for emergencies.
#+end_notes
* Benzo - intermediate
- LOAT
- TALO
- OTLA
#+begin_notes
LOATS is a good mneumonic to know for short-ish term benzos. Generally we recognize these as short acting but they are really intermediate acting as half-lives can be hours! They consist of Lorazepam, Oxazepam, Alprazolam, and Temazepam. The half lives are in the 10-20 hour range.
Insofar as half-lives are concerned, alprazolam has a half life of 12-15 hours, lorazepam 10-20 hours, oxazepam 3-21, and temazepam 8-15. So really it should be TALO rather than LOAT if you want to consider the upper limit of half-life and put them in order. Or lower limit arrangement would be OTLA.
Generally the reason these are called short acting is how they compare to actual long acting benzos.
#+end_notes
* Benzo - long
Everything else
#+begin_notes
If it's not in the above list, it's fair to say it's long acting. This includes clonazepam, diazepam, nitrazepam, chlordiazepoxide, flurazepam, etc. Just for the sake of equivalence in slides, clonazepam has a half-life of 30-40 hours and diazepam has a half-life of 20-50 hours, so a little wider range for diazepam. Clonazepam may be a bit more predictable that way.
#+end_notes
* Benzo in the elderly
Avoid
#+begin_notes
What about the elderly specifically. This lady is 75 years old, does that make a difference in terms of how we go about her management?
We'll refer to AGS's Beers Criteria which is intended for people 65+ and not in palliative or hospice situation. On page 7 of the 2019 publication, Beers criteria states Avoid use of benzos with strong recommendation with moderate quality of evidence. It mentions increased risk of cognitive impairment, delirium, falls, fractures, and MVAs. The recommendation applies to short and intermediate acting benzos. There are two situations that Beers criteria strongly recommends to avoid benzos with "high" quality evidence: history of falls or 2 or more drugs acting on CNS.
Beers criteria also notes continued use of benzos in elderly despite evidence of harms.
So why are they bad?
#+end_notes
* Why?
- increased sensitivity
- decreased metabolism
#+begin_notes
These are the reasons given in beers criteria for avoiding benzos in elderly specifically which leads us to its complications.
#+end_notes
* It's bad
- dependence
- falls and fractures
- cognitive decline
#+begin_notes
Long-term use is a red flag for dependence. There is also rebound anxiety, insomnia, strong desire to use benzos, use despite falls, in addition to other hypnotics, and use despite physician's recommendation. These are all things that needs to be considered as tingling spidey senses when a patient is on benzos as cues for dependence.
Falls happens through a number of mechanisms, including increased reaction time, disrupted balance and gait, and sedation. The risk of falls is dose-dependent as all the factors I mentioned are also dose-dependent. In some studies it has been estimated that risk of fall increases by 50%. They are also strongly associated with hip fractures, which then relates to studies demonstrating that 1/3 of patients with hip fractures die within one year. Most importantly, decreasing the dose appears to reduce the risk of falls.
Benzodiazepine use has also been associated with short-term cognitive deficits including memory, learning, attention, and visuospatial ability. Interestingly, in two studies, one RCT and a meta-analysis, it has been shown that in long-term users cognitive deficits remain and can potentially be irreversible. Although they didn't make any definitive conclusions and there was a lot of vague-ness in their conclusion. But it's something to keep in mind.
#+end_notes
* Really bad
/mortality/
#+begin_notes
And the worst of all, benzos have been independently associated with increase in all-cause mortality risk of 1.2-3.7 times higher rate per year compared to unexposed individuals. The caveat being it's unclear whether benzos are prescribed in that patient population or there is causal linkage.
#+end_notes
* Going back
- clonazepam
- tapered lorazepam
- supportive psychotherapy
#+begin_notes
Going back to the our patient. She was admitted, alprazolam was switched to clonazepam 0.5 bid keeping dose equivalence and PRN lorazepam 0.5 qid was started. She was continuously encouraged to stay away from lorazepam. Initially she was requesting lorazepam twice a day and was hyperfocused on lorazepam and clonazepam as the cure (red flag), but firm boundaries were set in combination with supportive psychotherapy and she eventually stopped requesting lorazepam, started engaging in activities, and partly due to the effect of time, she improved and was able to manage her anxiety without intermediate-acting benzos. She remains on clonazepam and continues to improve.
#+end_notes
* Discussion
#+begin_notes
And that's the story of our patient. Is there anything anyone would do differently?
#+end_notes
* Thank you