The Other "O" in Prescription Safety: Benz-O-diazepines (Threlfall, 12/2/2020)

Many thanks to psychiatrist Dr. Alex Threlfall for a compelling and important Grand Rounds this week on Benzodiazepine Use Disorder, or as he aptly put it, The Other "O" in Prescription Safety. This is SUCH an important topic and one that hasn't gotten enough of our attention over the last decade of opiate deprescribing. 

TAKE HOME POINT #1 Do NOT prescribe benzodiazepines. . .unless they are absolutely indicated. BZD role is limited, but there are some reasonable indications.

Reasonable indications for a short course of BZD are very limited. They include: 

1. crisis situations
2. acute bipolar mania (for induction of sleep)
3. alcohol withdrawal (maybe. . .but consider BZD sparing options) 
4. seizure disorders 
5. procedures 
6. some phobias (e.g. VERY limited amount for airplane, not to be combined with alcohol)

And if you do prescribe in any of the above scenarios:

• Use the lowest effective dose
• Avoid alprazolam
• Restrict prescription to 2 weeks or less

Here is why:

• After opioids, BZD are the drug class most commonly involved in intentional and unintentional pharmaceutical overdoses (29.4%)
• The overdose death rate involving BZD from 2011 to 2014 has increased five fold with opioids involved in 75% of these deaths (see diagram below from the NIH):

Dr. Threlfall outlined for us SIX areas of high risk with regards to BZD prescription

1. Mental health conditions associated with trauma (e.g. PTSD but also depression, anxiety, etc)
2. History of substance use disorder
3. Elderly
4. Compromised pulmonary function (e.g. moderate to severe COPD)
5. Women of child-bearing age
6. Patients suffering from chronic pain with or w/o opioid use

TAKE HOME POINT #2: Don't start any new prescriptions for BZD in anyone who meets any of the above criteria. 

Trauma is an integral part of our daily interaction with patients.

• physical or sexual abuse in childhood is reported by 20-50% of adults
• up to 70% of patients with depression, IBS, chronic pain, substance use report childhood physical or sexual abuse

There is NO evidence supporting the use of benzodiazepines in trauma. 

• not only are they ineffective, but they can lead to adverse outcomes in PTSD
• reducing efficacy of therapy
• prone to misuse and development of substance use disorder
• dangerous with substance use disorder often associated with trauma (ETOH, opioids)

Physical and psychological dependence can establish itself rapidly, especially in vulnerable patient populations. 

We should be very cautious and thoughtful about our use of BZD in the elderly-- in fact, we should really NOT be prescribing benzodiazepines

• in one study of elderly patients on BZD , fewer than 1% had been referred for psychotherapy despite carrying mental health diagnoses
• anxiety and insomnia are commonly diagnoses 
• there has been a 32% increase in continuing BZD prescriptions for elderly

BZD are associated with significant risks in the elderly

• falls
• hip fractures
• sedation
• cognitive impairment
• motor vehicle crashes

Department of Veteran Affairs- Benzodiazepine Educational Guide

Anxiety and insomnia are the two principal indications for prescribing benzodiazepines, but BZD are NOT first line for either of these conditions. 

Studies show that BZD are not effective for generalized anxiety disorder (GAD)

• 1st line: SSRI/SNRI +/- psychotherapy, buspirone
• 2nd line:  gabapentin, pregabalin, propranolol, clonidine*, amitriptyline/nortriptyline*, hydroxyzine, diphenhydramine (*indicates not for elderly)
• BZD are THIRD line for anxiety.

All professional organizations recommend against the use of benzodiazepines as first line therapy for insomnia

All recommend Cognitive Behavioral Therapy for Insomnia (CBTi) as first line

2nd line: melatonin, prazosin (if nightmare), trazodone>mirtazapine (at lower doses more effective for insomnia)>doxepin>amitriptyline/nortriptyline

3rd line: hydroxyzine/diphenhydramine, non-benzo (zolpidem/Ambien)> ezoplicone>zalaplon

BZD are FOURTH line for insomnia

If you ARE going to start a bzd:

• should be VERY rare
• only for short term relief of acute anxiety/panic (2-4 weeks) and chronic insomnia (1-2 weeks)
• get psychiatry consult to review chart
• have explicit conversation with patient that this is very short term, discuss exit strategies
• review risks with patient, including risk of dependence
• only one prescriber, urine tox screen, CURES, contract
• Recommended meds: lorazepam 2mg TDD, clonazepam 1.5mg TDD, diazepam 15mg TDD, temazepam 30mg TDD

Dr. Threlfall didn't have time to to talk about the specifics of BZD tapering, but please contact me if you want those slides.

He ended on the notion that direct patient education works. The 2014 EMPOWER study by Tennenbaum et al showed that simply informing patients of the risks of BZD motivates a significant percentage to initiate conversations about taper with their doctors AND successfully discontinue BZDs at 6 months (so cool!)

TAKE HOME POINT #3: So, yes, final take home point: talk to your patients about the risks of BZD. Maybe they will even be able to convince YOU they want to stop them.