When not to prescribe Benzodiazepines Youre getting nervous already, - - PDF document

APNA 30th Annual Conference Session 2025: October 20, 2016 Amberg 1

When not to prescribe Benzodiazepines…

You’re getting nervous already, aren’t you?

Alan “Tony” Amberg, MS MSN APN PMHNP‐BC Northwestern Memorial Hospital (Chicago) Lauren Prasek, MSN APN PMHNP‐BC Ronald Reagan UCLA Medical Center (Los Angeles)

Objectives

• After instruction, the learner will be able to:
• Identify common benzodiazepines and describe their mechanism of action
• Describe common uses vs. indicated uses for benzodiazepines (including

misuses) and side/adverse effects associated with benzodiazepine use medications Recognize appropriate uses of and alternatives to benzodiazepines

• Recognize appropriate uses of and alternatives to benzodiazepines

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A national addiction?

• 2008, Netherlands (pop. 16.3 million) ‐ >10m Rxs for benzos to 1.8 m

individuals

• 2009 stopped reimbursing for PCP Rxs of these meds
• Kollen et al (2012) studied the impact in 2009 and 2010
• Short‐term users slightly reduced # of days of Rx episode
• Long‐term users used as much, however, absolute # decreased 2.3%

A national addiction on both sides of the

• cean?
• 2015: First US national prescription epidemiology study, used 2008

sample to estimate 75 million Rxs

• However, national rate of use for age 65‐80 Men (6.1%) and Women

(10.8%) despite many warnings about use in elderly – mostly from non‐psychiatrist providers

• Highest rate of use (11.9%) observed among 80‐year‐old women

(Olfson, King, & Schoenbaum, 2015)

More fun benzo facts

• In all age groups, roughly 1/4 of pts receiving benzodiazepines

involved long‐acting agents

• Mean tx episode ranged from 224.9 days in young adults to 245.4

days in elderly

• Across all age and sex groups <10% were getting Rx from a

psychiatrist, esp. 65‐80 year olds (3.6%)

(Olfson, King, & Schoenbaum, 2015)

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GABA (γ‐amino butyric acid) Mechanism of action – Benzos, Barbiturates, etc.

GABA‐A ionotropic receptor/ligand‐gated ion channel

Five unit receptor (2 α units, 2 β units & 1 γ unit) with central chloride channel Modulates:

• Chloride ions inhibit neural action potentials (Na & K)
• Sedation
• Seizure
• Anxiety
• Spasm
• Perception of pain

Other GABA receptors

• GABA‐B G‐protein receptors to K channels
• (Baclofen, GHB)
• GABA αδ voltage dependent calcium channel receptors
• Gabapentin, Pregabalin

Modifying GABA receptors – old as civilization?

• Alcohol “v 1.0”– also hits Opioid and Cannabinoid receptors
• Barbiturates “v 2.0” (1864 – Adolf v Baeyer, 1904 1st marketed)
• High abuse/overdose potential (think Marilyn Monroe & Elvis Presley)
• Now for anesthesia induction or seizure
• Benzodiazepines “v 3.0” (1955 – Chlordiazepoxide or Librium, with Diazepam

following in 1963)

• …and then “Z‐drugs”, anti‐spasmodics, neuropathic pain…

9,000-Year-Old Beer Re-Created From Chinese Recipe John Roach for National Geographic News July 18, 2005

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Common Benzos

• Alprazolam (short) 6‐12 hr half‐

life/high‐potency

• Chlordiazepoxide (long‐acting) 30‐

200 hr/low potency

• Clonazepam (intermediate)hrs/high

potency

• Diazepam (long‐acting) 30‐100

hrs/low potency

• Diazepam metabolites

Chlorazepate 30‐200 hrs

• Oxazepam (short) 5‐15 hrs
• Temazepam (intermediate) ‐22 hrs
• Lorazepam (intermediate) 10‐20

hrs/high potency

• Midazolam (short) 1.8‐6

hrs/twilight sedation

This is not new information

“…there is no good evidence for their long term efficacy in the treatment of anxiety and insomnia…” “Adversely effects such as oversedation, tremor, ataxia and confusion are much more common in elderly patients. Ever since the benzodiazepines were first marketed 20 years ago their use has increased rapidly, and it is now estimated that between 12 and 16% of the adult population in developed countries use tranquillisers at some time each year.” (Lader & Petursson, 1983)

This is not new information

“Adverse effects include psychomotor impairment, especially in the elderly, and occasionally paradoxical excitement. With long term use, tolerance, dependence and withdrawal effects can become major

• disadvantages. Unwanted effects can largely be prevented by keeping

dosages minimal and courses short (ideally 4 weeks maximum), and by careful patient selection.” (Ashton, H., 1994)

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Indicated Uses

General

• Sedation Induction
• Seizure Prophylaxis & Treatment
• Muscle Spasm
• Anesthesia

Induction/Maintenance

• Tetanus

Psychiatric

• Alcohol or drug‐induced Seizures
• Anxiety (acute)
• Agitation (in some circumstances)
• Catatonia
• Generalized Anxiety Disorder (GAD)
• Insomnia (acute and sparingly)
• Involuntary Movement Disorders
• Panic Attacks (as a bridge only)

Short‐term use only (2 to 4 weeks)!

Common Misuses

• ANYTHING over 4 weeks
• Delirium (which is around ½ of general inpatient agitation cases)
• Geriatric (see Beers Criteria)
• GAD (indicated, but don’t do it)
• Insomnia
• PTSD (doesn’t work…really!)
• Panic Attacks

Adverse Effects

10 20 30 40 50 60 70 80 90 Respiratory Depression Memory Impairment Menstrual Irregularity Dysarthia Dizziness Drowsiness Alprazolam Diazepam Clonazepam Lorazepam

Tannenbaum, C., Martin, P., Tamblyn, R., Benedetti, A., & Ahmed, S. (2014)

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Alprazolam= Addictive

• High potency:

1 mg Alprazolam = 20 mg Diazepam

• Short to Intermediate half‐life

6‐12 hrs ‐ If given for sleep, there may be a hangover

• Quick onset/Abrupt termination – like a light switch so every 12 hrs

your patient will want more

• Unique mechanism of action: Triazolo – ring structure= unique

properties‐ antidepressant and antipanic‐ may cause mood cycling in Bipolar (mania)

• Mood disinhibition may emerge in Alprazolam
• (Keltner & Folks, 2005)

Benzo Withdrawal Symptoms

Psychiatric Effects

• Depression
• Insomnia
• Irritability
• Rebound Anxiety

Physiologic Effects

• Autonomic Instability
• Gastrointestinal
• Musculoskeletal
• Neurologic
• Tolerance

Benzodiazepine Use Disorder Treatment

• Prevention! ‐ Stick to the guidelines 2‐4 weeks use only and as a bridge to

longer acting non‐dependence forming agents (Ashton, H. 2005)

• Taper dose by 25% q 2‐3 weeks. Determine if the patient needs a longer

acting or low potency alternative. Substitute with Diazepam – also consider Pregabalin

• Let patients guide the taper – do not pressure the patient
• (Ashton, C.H. 2013)
• CBT has moderate evidence of efficacy with benzo taper at 3 months

(Cochrane, 2015)

• A Spanish study showed that training the PCPs in dose reduction with

either written information or face‐to‐face follow produced 45% discontinuation at 12 mos vs 15% with TAU. (Vicens, Bejarano et al, 2014)

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Reminder…

In the elderly

• Impairment to cognitive function
• Risk of falls
• MVA
• Increased risk of dependence
• Increased risk of dementia and death

(Olfson, King, & Schoenbaum, 2015)

Less is more…. In individuals with Schizophrenia

Antipsychotic, antidepressant and benzodiazepine polypharmacy –

• aggressive and impulsive behavior
• 283% suicidal deaths and 60%

non‐suicidal deaths

• Unfortunately, too often given

long term, so when you see a psych patient…

(Tiihonen, J et al, 2012)

Less is more….

Common Uses & Alternatives

Common Responses to…

Anxiety Disorders

What is usually used? Alprazolam/Clonazepam Lorazepam/Diazepam What are the alternatives? SSRIs/SNRIs Buspirone (Buspar)

Non‐pharmacologic Responses…

Attention to environment Psychotherapy – e.g. CBT Exercise Yoga/Relaxation Training Mindfulness‐Based Stress Reduction Emotional response to illness Family needs Financial implications Addressing adequate sleep Nutrition Endocrine

Common Uses & Alternatives

Common Responses to…

Insomnia

What is usually used? Alprazolam/Clonazepam/ Lorazepam Z‐drugs (Ambien, Lunesta, Sonata) Low‐dose Quetiapine (Seroquel) What is often ignored in the environment? No definite light/dark cycle Disturbances in sleep Lack of ambulation Failing to address patient anxiety

Preferred Responses…

Attention to environment Attention to patient/family emotional state Delirium? Possible low dose antipsychotics No benzos or anticholinergics Melatonin Agonists Hypnotic Antidepressants Alpha 2 agonists/Alpha 1 antagonists Remove medications that disturb sleep architecture LIKE EtOH or most benzos

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Common Uses & Alternatives

Common Responses to…

Withdrawal

What is usually used? Lorazepam: ½ life 12 hrs, safer for liver Diazepam: ½ life 30‐100 hrs, self‐ taper Chlordiazepoxide – ½ life 3‐200 hrs, less sedating What are the alternatives? Scheduled taper & Symptom triggered dosing with CIWA OR Benzo‐sparing regimens

Preferred Responses…

High risk for DTs or seizure – use scheduled benzo taper or Diazepam Lond Mitigate other symptoms (e.g. nausea, abdominal cramping) Benzo withdrawal done over months & outpatient Gabapentin Clonidine/Dexmadetomidine Topiramate/ Deapkote Don’t forget at discharge: Naltrexone – hepatic metabolism Acamprosate – renal metabolism

Other Uses

Seizures

• Should be used for acute

situations only

• Long‐term use for prophylaxis

should be managed by a neurologist

Acute Sedation

• Agitation in non‐demented, non‐

delirious patient

• If patient is actively psychotic – give

with an antipsychotic (except Olanzapine) for synergistic effect. Do not give benzodiazepine by itself

• Do not give to patient just because

they are angry or anxious – patients have a right to their feelings

• The exception is Procedures (e.g. MRI)

In Summary

• Powerful medications with high dependence & abuse potential
• Seductive to both patient & provider; they appear to provide an easy

solution

• Work by enhancing GABA – body’s major inhibitory neurotransmitter
• Short‐term use ONLY
• Common long‐term misuse causes major adverse effects
• Easy to start, tough to stop – talk to psychiatry for safer alternatives

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References

• Ashton, C.H. (2013). Benzodiazepines: how they work and how to withdraw. http://benzo.org.uk/manual/. Retrieved September 8, 2015.
• Ashton, H. (2005). The diagnosis and management of benzodiazepine dependence. Curr Opin Psychiatry, 18(3), 249‐55. Retrieved September 8, 2015.
• Dunlop, B., & Davis, P. (2008). Combination treatment with benzodiazepines and SSRIs for comorbid anxiety and depression: a review. Primary Care Companion To

The Journal Of Clinical Psychiatry, 10(3), 222‐228.

• Keltner, N., & Folks, D. (2005). Psychotropic Drugs (4th ed.). Philadephia, PA: Elsevier.
• Kollen, B., van der Veen, W. J., Groenjhof, F., Donker, G. A., & ven der Meer, K. (2012). Discontinuation of reimbursement of Benzodiazepines in the Netherlands:

does it make a difference? BMC Family Practice, 13(1), 111‐117. doi:10.1186/1471‐2296‐13‐111.

• Longo, L., & Johnson, B. (2000). Addiction: part I. Benzodiazepines ‐‐ side effects, abuse risk and alternatives. American Family Physician, 61(7), 2121.
• McCall C, Winkelman J. The Use of Hypnotics to Treat Sleep Problems in the Elderly. Psychiatr Ann. 2015; 45: 342‐347. doi: 10.3928/00485713‐20150626‐05.
• Olfson M, King M, Schoenbaum M. Benzodiazepine Use in the United States. JAMA Psychiatry. 2015; 72(2):136‐142. doi:10.1001/jamapsychiatry.2014.1763.
• NRHA Drug Newsletter, April 1985 and Benzodiazepines: How they Work & How to Withdraw (The Ashton Manual), 2002.
• Pimlott, N. J. G., Hux, J. E., Wilson, L. M., Kahan, M., Li, C., & Rosser, W. (2003). Educating physicians to reduce benzodiazepine use by elderly patients: a randomized

controlled trial. CMAJ: Canadian Medical Association Journal, 168(7), 835‐839.

• Rossat, A., Fantino, B., Bongue, B., Colvez, A., Nitenberg, C., Annweiler, C., & Beauchet, O. (2011). Association between benzodiazepines and recurrent falls: A cross‐

sectional elderly population‐based study. Journal Of Nutrition, Health & Aging, 15(1), 72‐77. doi:10.1007/s12603‐011‐0015‐7.

• Sirdifield, C., Anthierens, S., Creupelandt, H., Chipchase, S. Y., Christiaens, T., & Siriwardena, A. N. (2013). General practitioners' experiences and perceptions of

benzodiazepine prescribing: Systematic review and meta‐synthesis. BMC Family Practice, 14(1),191‐215. doi:10.1186/1471‐2296‐14‐191.

• Tannenbaum, C., Martin, P., Tamblyn, R., Benedetti, A., & Ahmed, S. (2014). Reduction of Inappropriate Benzodiazepine Prescriptions Among Older Adults Through

Direct Patient Education: The EMPOWER Cluster Randomized Trial. JAMA Internal Medicine, 174(6), 890‐898. doi:10.1001/jamainternmed.2014.949.

• Tiihonen, J., Suokas, J., Suvisaari, J., Haukka, J., & Korhonen, P. (2012). Polypharmacy with antipsychotics, antidepressants, or benzodiazepines and mortality in

schizophrenia. Archives Of General Psychiatry, 69(5), 476‐483.

• Vicens, C., Bejarano, F., Sempere, E., Mateu, C., Fiol, F., Socias, I., & ... Leiva, A. (2014). Comparative efficacy of two interventions to discontinue long‐term

benzodiazepine use: cluster randomised controlled trial in primary care. British Journal Of Psychiatry, 204(6), 471‐479. doi:10.1192/bjp.bp.113.134650.