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Discontinuing Benzo’sThe Holy Grail of De-prescribing

Moataz DaoudPharm D. StudentAugust 18, 2014

+Learning Objectives

To explore the impact of the overuse benzodiazepines

To evaluate the different strategies for benzodiazepine discontinuation

To apply the current evidence to a real patient case

+Why Do We Care?

Promoted as a “safe” alternative to barbiturates and other hypnotics Very high therapeutic index Thought to have lower abuse potential

Now use is prevalent 19% of 65-74 YO’s and 25% >85 YO are on benzos (CIHI

2010) 4 million scripts for benzos are filled in Ontario each year

Benzo’s identified as a significant cause of morbidity in the elderly Study by Wagner et al. found that benzo exposure

increases fracture risk IRR = 1.24; 95% (1.06-1.44)

+Case

Mrs. CR 78 YO female

HPI: On bus to bridge, fell asleep, difficult to arouse, pin-point pupils… Bus driver called EMS and mother was brought to the ED Treated for opioid toxicity in ER, transferred to GIM

+Review of Systems

Vitals Afebrile HR: ~85 BP: ~110/60 RR: 20

CNS: Mildly Sedated All other systems unremarkable

+Case (cont’d)

Allergies: NKDA

Social Hx Non Smoker No EtOH Lives alone with support from children

+Benzodiazepine use

DPV indicated that patient was on clonazepam 6 months ago Clonazepam 4 mg PO QHS

When asked about this, the patient stated that the doctor discontinued the benzo after a fall

She felt “really anxious” and was unable to sleep Started getting clonazepam from a friend in her bridge club

+DTPs

Mrs. CR is at risk of benzodiazepine withdrawal secondary to abrupt cessation of therapy

Mrs. CR is at increased risk of sedation and falls secondary to benzodiazepine use

+Background

Increases the conduction of chloride ions across the neuronal cell membrane.

BDZ bindsα/γ α1, α2, α3 and α5

(histidine residue) α4, α6 (arginine

residue)

Beth Sproule, PharmD, Sedative Hypnotics lecture (2013)

+Background

Kevin Robillard, M.Sc. Pharmacotherapy of Anxiety and Sleep lecture, 2012

+Background

Kevin Robillard, M.Sc. Pharmacotherapy of Anxiety and Sleep lecture, 2012

+Background

Action on GABA has lead to many indications Generalized anxiety disorder, panic disorder Insomnia Alcohol withdrawal Muscle relaxant Seizures Pre-operative sedation

+BEERS Criteria

Avoid benzodiazepines (any type) for treatment of insomnia, agitation, or delirium.

Older adults have increased sensitivity to benzodiazepines and decreased metabolism of long-acting agents. In general, all benzodiazepines increase risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents in older adults.

May be appropriate for seizure disorders, rapid eye movement sleep disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, periprocedural anesthesia, end-of-life care.

+Withdrawal

+What questions do we need to ask?

1. What is she taking it for? For insomnia

2. What is her total exposure (dose and duration)? She was started on clonzaepam 2 years ago On 4 mg PO QHS

3. What is her liver and renal function like? CrCl = 60 ml/min LFT’s normal, no Hx of liver dysfunction

+BDZ Taper Commandments

1. Go SLOW!

2. Put the patient in control of the taper!

3. Taper by no more than 5 mg diazepam equivalent per week

4. Use scheduled doses Avoid “rescue” pills

5. Halt or reverse taper if severe anxiety or depression occurs

6. Schedule follow-up visits q. 1–4 weeks

+Which BDZ is best

Dr. Heather Ashton, The Ashton Manual

+Taper Schedule

Patient on 4 mg of clonazepam = 40 mg of diazepam

Decrease dose by 4 mg/weeks (10%) Slow pace to 1-2 mg /week when pt reaches 20 mg/day

Taper by 10% of the dose every 1–2 weeks until the dose is at 20% of the original dose; then taper by 5% every 2–4 weeks

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+Patient Education

Body may need to readjust to the absence of the drug

~2/3 experience withdrawal symptoms

The symptoms are temporary

Rebound is not the same as recurrence Rebound is short-lived

Discontinuing BDZ is important Minimize sedation reduce falls risk

+Why not Clonazepam

It is not always necessary to change drugs

Clonazepam is a longer acting agent

It is available as 0.25 mg, 0.50 mg, 1.0 mg, 2.0 mg 0.25 mg is not a benefit Dose titration is more difficult Shorter half-life than diazepam!

*Lower risk of accumulation than diazepam!

+What if the patient starts experiencing withdrawal?

Maintain current dose for an additional 1-2 weeks or until the symptoms subside

Avoid going back or using “rescue” pills

If necessary increase dose by 50% of the last dose reduction increment Use smaller increments for dose reduction going forward

+References

1. Lader, Malcolm, Andre Tylee, and John Donoghue. "Withdrawing benzodiazepines in primary care." CNS drugs 23.1 (2009): 19-34.

2. Morin, Charles M., et al. "Randomized clinical trial of supervised tapering and cognitive behavior therapy to facilitate benzodiazepine discontinuation in older adults with chronic insomnia." American Journal of Psychiatry 161.2 (2004): 332-342.

3. Morin, Charles M., et al. "Long-term outcome after discontinuation of benzodiazepines for insomnia: a survival analysis of relapse." Behaviour research and therapy 43.1 (2005): 1-14.

4. Chen Lori, Farrell Barbara, Ward Natalie, et al. Discontinuing benzodiazepine therapy : An interdisciplinary approach at a geriatric day hospital. Canadian Pharmacists Journal: November 2010, Vol. 143, No. 6, pp. 286-295.e1.

5. Clegg A, Young JB. Which medications to avoid in people at risk of delirium : a systematic review. Age Ageing. 2011 Jan;40(1):23-9. (opiates and benzos)

6. Dr. Heather Ashton, The Ashton Manual: http://www.benzo.org.uk/manual/bzsched.htm#s1

7. Kalvik 1995, Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain, Canadian Pharmacists Association 1999

8. Anita K. Wagner, PharmD, MPH, DPH; Fang Zhang et al., Benzodiazepine Use and Hip Fractures in the Elderly: Arch Intern Med. 2004;164:1567-1572

9. Beth Sproule, PharmD, Sedative Hypnotics lecture (2013)

10. LANCE P. LONGO, M.D, Addiction: Part I. Benzodiazepines—Side Effects, Abuse Risk and Alternatives, Am Fam Physician. 2000 Apr 1;61(7):2121-2128.

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QUESTIONS?

+Efficacy of Pharmacologic Agents in the Treatment of Anxiety Disorders

LANCE P. LONGO, M.D, Addiction: Part I. Benzodiazepines—Side Effects, Abuse Risk and Alternatives, Am Fam Physician. 2000 Apr 1;61(7):2121-2128.