Managing Benzodiazepine Use in Older Adults

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This tool is designed to help primary care providers assess and discuss with their patients 65 years of age or older, the potential risks and benefits of benzodiazepines. This tool also contains steps to support primary care providers in safely discontinuing, starting or continuing to prescribe benzodiazepines for their older patients.

Potential risks and benefits of benzodiazepines

Benzodiazepines are not the preferred treatment for anxiety disorders, insomnia or panic disorder among older adults. 1-4 As patients age, their bodies respond to medications differently, and some medications become less safe than others.

It is important to re-evaluate all medications as a patient approaches the age of 65. Re-evaluating the risks and benefits of concurrent medications is a routine part of medicine. It is particularly important to review the use of benzodiazepines, given the patient safety risks associated with the use of this medication in advanced age, as discussed in this tool.

Potential Risks
  • Older adults have an increased sensitivity to benzodiazepines and decreased metabolism of long-acting agents
  • All benzodiazepines increase the risk of cognitive impairment, delirium, falls, fractures and motor vehicle accidents in older adults
  • Insomnia: NNH for any harm at 2 weeks = 63
Potential Benefits
  • Anxiety disorders: NNT at 4-6 weeks = 75
  • Insomnia: NNT at 2 weeks = 133
    • 34.2 additional minutes of sleep
    • 0.60 less awakenings per night
  • Panic disorder: NNT (timeframe unknown) = 56
Determine whether a benzodiazepine is appropriate or problematic7
Identify patients

Opportunistically, when the patient:8, 9

  • Comes in for a preventative health exam
  • Comes in for a prescription renewal or refill
  • Has had a recent hospitalization
  • Has had a recent fall
  • Is admitted to long-term care
  • Presents with new cognitive concerns or early onset dementia
  • Reports driving difficulty or their family, caregivers or friends reports concerns
  • Demonstrates rapid escalation of medication use
  • Has an active substance use disorder that could trigger inappropriate or problematic use of benzodiazepines
  • Has a potential benzodiazepine use disorder13Possible indications of benzodiazepine use disorder:
    • Deteriorating function despite increasing dose
    • Dishonesty with respect to prescriptions (e.g. frequent reports of loss or theft of medications and/or routine early refill requests)
    • Involvement with law-enforcement
    • Non-oral route of administration
    • Active misuse of another substance
    • Diversion or other substance-dealing behaviour If patient presents with possible indications of a benzodiazepine use disorder, diagnose the patient using the DSM-5 criteria for Sedative, Hypnotic, or Anxiolytic Use Disorder.

Proactively

  • Set EMR reminders or patient record flags as a reminder to review a patient’s benzodiazepine use during their next appointment. 8
  • Encourage patients to bring up their use of benzodiazepines during their next appointment:
    • mail or hand-out patient material to rostered patients ages 65 or over
    • put waiting room patient posters up or provide screening questions while patients wait for their appointments. This type of patient material is available from the Centre for Effective Practice and the Canadian Deprescribing Network.
Discuss their use of benzodiazepines

Ask patients what they take the benzodiazepine for: “What concerns did you originally start the benzodiazepine for? Have the concerns that led to your initial benzodiazepine prescription changed?” 10

Highlight the benefits versus risks of benzodiazepine use for older adults:

  • “Although benzodiazepines sometimes offer small benefits in the short term, they stop working and become harder to wean from over time. Despite this, the serious side effects of taking benzodiazepines remain, such as cognitive impairment, delirium, falls, fractures and increased risk of motor vehicle accidents.” 7
  • “To maintain your independence, it is important to reduce or remove any medications that increase your risk of cognitive impairment, delirium, falls, fractures and motor vehicle accidents.” 7
  • “While taking a benzodiazepine you have an increased risk of side effects: 11
    • 5 times higher risk of memory and concentration problems
    • 4 times higher risk of daytime fatigue
    • 2 times higher risk of falls and fractures (hip, wrist)
    • 2 times higher risk of experiencing a motor vehicle accident”
  • “The benzodiazepine may cause problems with your memory and concentration which could result in an assessment of your driving privileges.” 9
Consider benzodiazepine appropriateness

If the patient is taking/starting it for seizure disorders / alcohol withdrawal / Short-term use (<4 weeks):

Discontinuing Benzodiazepines

Important information to collect before starting a taper

Current dose and duration, including prn use of benzodiazepine

  • Discontinuation with no taper is possible if the benzodiazepine has been taken for <3 weeks 14
  • Individuals taking the equivalent of ≥60mg diazepam daily (see Benzodiazepines available in Ontario), or with a history of serious withdrawal reactions, should be hospitalized during acute withdrawal and tapering should be slower 14

All prescribed and over-the-counter medications that the patient is currently taking, including supplements, vitamins, and naturopathic treatments

History of previous non- pharmacological and pharmacological alternatives tried for anxiety disorders, insomnia or panic disorder

  • Understand what the patient means by “tried” and consider if the duration “tried” is long enough to evaluate efficacy/side effects
  • An adequate trial of non- pharmacological and pharmacological alternatives is approximately 6-8 weeks

Substance use history (e.g. alcohol, cannabinoids, caffeine, nicotine)

History of adverse events (e.g. delirium, dementia or cognitive impairment, falls, fractures or motor-vehicle accidents)

Baseline assessment of anxiety disorders, insomnia or panic disorder

Tapering Steps
  • Engage patients in developing a clear plan for tapering, incorporating goals and preferences regarding benzodiazepine use7
    • Discuss a goal of discontinuation versus lowest possible dose : If a medication cannot be completely discontinued, a decrease in dose is still a win!
    • Ensure patients know what is required of them (e.g. schedule for primary care provider visits and schedule for picking up prescriptions at designated pharmacy)
    • Reassure patients that they have control in the taper; taper can go as slow as they need and can be paused and adjusted as needed
  • Establish the formulation to be used for tapering
    • See Benzodiazepines available in Ontario if switching patient to another benzodiazepine before tapering
    • There is insufficient evidence to support the use of one particular benzodiazepine over another (or for long- vs. short-acting benzodiazepines) for a tapering schedule7
    • Switching to long-acting benzodiazepines for a taper:
      • Switching to long-acting benzodiazepines may be done (e.g. diazepam, clonazepam), but this has not shown to reduce the incidence of withdrawal symptoms or improve cessation rates more than tapering shorter-acting benzodiazepines 7
      • Long-acting benzodiazepines do however offer advantages when tapering, including fewer rebound symptoms, constant drug levels and ease of formulation 14, 19, 20
      • To reduce the severity of withdrawal symptoms, keep a patient on a long-acting benzodiazepine for at least 2 months following a switch (from a short-acting benzodiazepine) and before initiating a taper from the long-acting benzodiazepine 14
  • Establish the dosing interval
    • Scheduled doses are preferred over prn doses (to help with the withdrawal)
    • Keep the dosing interval constant (e.g. bid)
  • Establish the rate of the taper based on the patient’s health and preferences, as well as formulations available for the current benzodiazepine (see Benzodiazepines available in Ontario)
    • For older adults, it is recommended to taper the benzodiazepine dose slowly: 25% reduction every 2 weeks and then a slower taper of 12.5% every 2 weeks near the end 7
    • For long-acting benzodiazepines: 21 Taper by no more than diazepam 5mg or clonazepam 0.25mg equivalent/week
    • Alternative rates for tapering:
      • Taper by 10% every 1–2 weeks until 20% of the original dose is reached, then taper by 5% every 2–4 weeks14
      • For those experiencing severe side effects or severe anxiety, consider a slower taper of 10% every 2 weeks 14
      • For those taking a benzodiazepine for panic disorder, taper the weekly dose by a maximum of 10% per week over a period of 2–4 months
      • For those who have been taking a long half-life benzodiazepine for only a short-term (e.g. up to 4 weeks of clorazepate or clonazepam), taper over 1 week
      •  Alprazolam: for doses <4mg/day, taper by no more than 0.5mg every 3 days or no more than 0.25mg every week 14
      • Alprazolam: for doses ≥4mg/day, even slower tapers over 3+ months are required (e.g. 0.5mg every 2–3 weeks, then slow to 0.25mg every 2–3 weeks when at 2mg/day) 14
  • Contact the patient’s pharmacy to discuss the tapering plan (by phone and/or fax depending on what is feasible)
    • Discuss with the pharmacist any pill splitting or liquid formulations necessary to accommodate tapering doses as well as packaging options for older adults (e.g. dosette or blister pack)
    • For long-acting benzodiazepines: 21 instruct the pharmacist to dispense daily, weekly or every 2 weeks depending on the dose and patient reliability

Consider cognitive behaviour therapy to improve tapering success rates

  • Cognitive behaviour therapy has the highest success rate for patients discontinuing benzodiazepines compared to usual care or other prescribing interventions (see Patient resources, services and supports) 7
  • The use of pharmacological adjunctive agents has limited evidence to support success
  • Decrease patient’s dose by 25% (or decided upon rate) every 2 weeks until dose is close to end goal (discontinuation or lowest possible dose), then slow the dose reduction to 12.5% (or decided upon rate) every 2 weeks until the end goal is reached. 7
    • For long-acting benzodiazepines: 21 slow the pace of the taper once the dose is below 20mg of diazepam equivalent (e.g. 1–2 mg/week); adjust rate of taper according to patient’s symptoms.
  • Schedule follow-up appointments with patient for every 1-2 weeks (in-person or over the phone) to monitor for expected benefits as well as severity and frequency of adverse drug withdrawal symptoms. 7
  • See II. Monitoring during a taper
  • If withdrawal symptoms are bothersome for a patient or if the taper is not going well, consider maintaining the current dose for an additional 1-2 weeks before attempting the next dose reduction, then continue to taper at a slower rate if appropriate 7
Monitoring the taper 7,12

During a taper, monitor a patient for expected benefits as well as adverse drug withdrawal symptoms and manage accordingly. If a patient is at high risk of withdrawal symptoms, refer to a supervised setting during taper initiation.

Monitor for: 7, 12


Expected benefits

 

  • Less daytime sedation
  • Improved cognition
  • Fewer falls
  • Fewer fractures
  • Fewer motor vehicle accidents
  • Improved function
  • Fewer respiratory exacerbations


Common withdrawal symptoms

 

  • Rebound anxiety disorders and/or panic disorder
    • Use validated assessment tools such as, the GAD-7 and PHQ (PHQ section 4 on panic disorder)15
  • Rebound insomnia
  • Irritability
  • Sweating
  • Gastrointestinal symptoms (i.e. diarrhea, abdominal cramps, nausea and vomiting)
  • Chills
  • Tremors
  • Dizziness
  • Visual distortion (patient should be told to see their primary care provider if they are experiencing visual distortion)
  • Tinnitus


Severe withdrawal symptoms*

  • Agitation
  • Confusion
  • Disorientation
  • Depersonalization
  • Delirium
  • Seizures
  • Unstable vital signs

 

*Severe withdrawal symptoms do not appear to occur with tapering but have been reported rarely in patients stopping very high doses without tapering or who have underlying seizure disorders 7

Manage withdrawal symptom(s)
  • If withdrawal symptoms are bothersome for a patient, consider maintaining the current dose for an additional 1–2 weeks before attempting the next dose reduction, then continue to taper at a slower rate if appropriate. 7
  • Currently, no medications are recommended or approved for the management of benzodiazepine withdrawal after long-term use. 27 The following are temporary solutions (off-label) for acute relief of withdrawal symptoms that should be used with caution among older adults. These temporary solutions are based on clinical practice as quality evidence in this area is limited. If prescribing any of the following, use clinical judgment regarding the patient’s ability to tolerate these medications and closely monitor the patient.

First try to slow down or pause the taper to manage withdrawal symptoms, then consider the following alternatives for indicated symptoms:

  • Oxybutynin* 2.5–5mg bid prn (short-term use)
  • Ensure patient is well-hydrated
  • Stop stool softeners and/or laxatives (e.g. sennosides, docusate sodium, lactulose), if applicable
  • Loperamide (if necessary) 4mg STAT, then 2mg after each unformed stool up to a maximum of 16mg per day
  • If BP >90/50 mmHg, may give clonidine* 0.1mg (check BP and HR 1 hour later and if BP <90/50, HR <50 or dizziness, do not prescribe further); may titrate up to qid prn, then taper

* Appears in 2019 AGS Beers Criteria® – the Beers Criteria is published by the American Geriatrics Society and is a list of potentially inappropriate medications in older adults 28

Alternatives to Benzodiazepines for Anxiety

The following pages outline many of the non-pharmacological and pharmacological alternative therapy options to benzodiazepines for older adults, along with the level of evidence and adverse effects associated with each therapy. Non-pharmacological alternatives are the preferred treatment for anxiety disorders, insomnia or panic disorder among older adults. As patients age, their bodies respond to medications differently, making them more susceptible to adverse events and drug-drug interactions. If using pharmacological alternatives in older patients, consider patient factors and use the “start low, go slow” approach.

Non-pharmacological 1,2
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  • Cognitive behavioural therapy

    Level of evidence
    •••

    Efficacy of psychological treatment is similar to that of pharmacotherapy for the treatment of anxiety disorders in older patients

  • Progressive muscle relaxation

    Level of evidence
    •••

    Efficacy of psychological treatment is similar to that of pharmacotherapy for the treatment of anxiety disorders in older patients

  • Psychological therapy (supportive psychotherapy)

    Level of evidence
    ••

    Efficacy of psychological treatment is similar to that of pharmacotherapy for the treatment of anxiety disorders in older patients

  • Physical activity

    Level of evidence

    Physical activity: 2.5 hours of moderate to higher intensity aerobic activity/week in bouts of 10minutes or more33

Level of evidence:
· · · = meta-analysis or at least 2 randomized controlled trials that included a placebo condition,
· · = at least 1 randomized controlled trial with placebo or active comparison condition,
· = uncontrolled trial with at least 10 subjects

Pharmacological
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  • First-line treatment
    Escitalopram and sertraline
    (SSRIs)

    Level of evidence
    •••

    Adverse effects

    • Insomnia
    • Somnolence
    • Sedation
    • Nausea
    • GI
    • Sexual Dysfunction
    • Qt prolongation
    • Dizziness
    • Dry mouth
    • Hyponatremia
    Additional Information
  • First-line treatment
    Duloxetine and venlafaxine ER
    (SNRIs)

    Level of evidence
    •••

    Adverse effects

    • Insomnia
    • Sleep disturbances
    • Sedation
    • Nausea
    • GI
    • Decreased appetite
    • Increased BP
    • Dizziness
    • Hyponatremia
    Additional Information
  • First-line treatment
    Pregabalin

    Level of evidence
    •••

    Adverse effects

    • Sedation
    • Nausea
    • GI
    • Dizziness
    • Dry mouth
    Additional Information
  • Second-line treatment
    Bupropion SR/XL

    Level of evidence
    •••

    Adverse effects

    • Insomnia
    • GI
    • Decreased appetite
    • Decreased activity
  • Third-line treatment
    Citalopram (SSRI)

    Level of evidence

    Adverse effects

    • Insomnia
    • Sleep disturbances
    • Somnolence
    • Sedation
    • Nausea
    • GI
    • Sexual dysfunction
    • Qt prolongation
    • Dizziness
    • Dry mouth
    • Hyponatremia
    Additional Information
  • Third-line treatment
    Trazodone

    Level of evidence
    ••

    Adverse effects

    • Nausea
    • Priapism in men (rare)
    • Orthostatic hypotension
  • Third-line treatment
    Mirtazapine

    Level of evidence

    Adverse effects

    • Sedation
    • Increased appetite & weight
    • Qt prolongation
    • Dizziness
    Additional Information
  • Third-line treatment
    Fluoxetine (SNRI)

    Level of evidence

    Adverse effects

    • Insomnia
    • Sleep disturbances
    • Somnolence
    • Sedation
    • Nausea
    • GI
    • Anorexic & stimulating
    • Sexual dysfunction
    • Qt prolongation
    • Dizziness
    • Dry mouth
    • Hyponatremia
    Additional Information

Level of evidence:
· · · = meta-analysis or at least 2 randomized controlled trials that included a placebo condition,
· · = at least 1 randomized controlled trial with placebo or active comparison condition,
· = uncontrolled trial with at least 10 subjects

Alternatives to Benzodiazepines for Insomnia

The following pages outline many of the non-pharmacological and pharmacological alternative therapy options to benzodiazepines for older adults, along with the level of evidence and adverse effects associated with each therapy. Non-pharmacological alternatives are the preferred treatment for anxiety disorders, insomnia or panic disorder among older adults. As patients age, their bodies respond to medications differently, making them more susceptible to adverse events and drug-drug interactions. If using pharmacological alternatives in older patients, consider patient factors and use the “start low, go slow” approach.

  • Cognitive behavioural therapy for insomnia is more effective than pharmacological therapy for the short- and long-term management of insomnia in older adults.17
  • There are no medications for primary or chronic insomnia in older adults that are proven to be safe and effective.7
Non-pharmacological
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  • Cognitive behavioural therapy

    Level of evidence
    ••
    to •••

    Notes

    • Restructures maladaptive beliefs regarding health and daytime consequences of insomnia
  • Good sleep hygiene

    Level of evidence
    ••

    Notes

    • Reduces behaviours that interfere with sleep drive or increased arousal
  • Sleep restriction

    Level of evidence
    to ••

    Notes

    • Increases sleep drive and stabilizes circadian rhythm
  • Stimulus control

    Level of evidence
    to ••

    Notes

    • Reduces arousal in sleep environment and promotes the association between bed and sleep
  • Progressive muscle relaxation

    Level of evidence
    to ••

    Notes

    • Reduces physical and psychological arousal in sleep environment
Pharmacological
Nonbenzodiazepine benzodiazepine receptor agonist hypnotics (Z-drugs)
  • Z-drugs have adverse events similar to those of benzodiazepines in older adults (e.g. delirium, falls, fractures, daytime sedation, increased emergency room visits/hospitalizations, motor vehicle crashes and minimal improvement in sleep latency and duration). Z-drugs should be avoided in older adults or those with a history of these adverse events. 28, 35, 36
  • Discontinuing Z-drugs: 14
    • Tapering is recommended when discontinuing after use for more than 4 weeks
    • To help lessen the more common withdrawal symptom of rebound insomnia:
      • Gradually reduce the dose by 50% every week until lowest available dose is being used, then reduce use to every other day, then use only as needed and then discontinue use completely OR
      • Gradually reduce the dose by 25% every 2 weeks and then slow the taper to 12.5% every 2 weeks near the end 7
  • Educate the patient that some sleep difficulty should be expected but that it should resolve within a week

Increased risk: Z-drugs and complex sleep disorders41

  • Serious injuries and death from complex sleep behaviors have occurred in patients who have taken Z-drugs with and without a history of such behaviors, even at the lowest recommended doses, and the behaviors can occur after just 1 dose
  • Health care professionals should not prescribe Z-drugs to patients who have previously experienced complex sleep behaviors after taking these medications
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  • Z-drugs
    Zopiclone*

    Level of evidence
    to ••

    Formulations

    • 3.75mg, 5mg, 7.5mg ^
    • Older patient max: 5mg/day

    Notes

    • Indicated for insomnia but avoid in older adults 28
    • Improves sleep onset latency (~19 min), total sleep time (~45 min), wake after sleep onset (~11 min)
    • Risk of physical tolerance and dependence
  • Z-drugs
    Zolpidem**

    Level of evidence
    to ••

    Formulations

    • 5mg, 10mg
    • Older patient max: 5mg/day

    Notes

    • Indicated for insomnia but avoid in older adults 28
    • Improves sleep onset latency (~15 min), total sleep time (~23 min)
    • Oral disintegrating tablet – cannot be split
    • Less chance of morning hang-over effect than zopiclone
    • Risk of physical tolerance and dependence
  • Doxepin (TCA)

    Level of evidence
    to ••

    Adverse effects

    • Anticholinergic side effects with higher dose

    Notes

    • Appears in 2019 AGS Beers Criteria®* (for doses greater than 6mg)
    • 3mg: improves total sleep time (~12 min), wake after sleep onset (~10 min)
    • 6mg: improves total sleep time (~17 min), wake after sleep onset (~14 min)
    • Not to be taken within 3 hours of a meal due to delayed absorption and the potential for next day drowsiness
    • Minimal risk of physical tolerance/dependence; consider doxepin if substance abuse or dependence is a concern
  • Trazodone

    Level of evidence
    to ••

    Adverse effects

    • Orthostatic hypotension
    • Priapism in men (rare)

    Notes

    • Trazodone is indicated for depression; limited evidence for insomnia
    • Lower risk of morning hangover effect due to a short half-life
    • Minimal risk of tolerance/dependence
    • Low anticholinergic activity
  • Melatonin

    Level of evidence
    to ••

    Adverse effects

    • Fatigue
    • Headache
    • Dizziness
    • Irritability
    • Abdominal cramps

    Notes

    • Modest effect on sleep (may decrease sleep onset latency [~7 min]; increases total sleep time [~8 min], and improves sleep quality)
    • No apparent physical tolerance and dependence
    • Purity concerns
  • Valerian root

    Level of evidence
    to ••

    Adverse effects

    • Headache
    • Dizziness
    • Nausea
    • Upset stomach
    • Hepatotoxicity (rare)

    Notes

    • Limited evidence for insomnia
    • Purity concerns

^ Scored
* Covered by Exceptional Access Program39
** Possibly covered by Exceptional Access Program40
Level of evidence:
· · · = meta-analysis or at least 2 randomized controlled trials that included a placebo condition,
· · = at least 1 randomized controlled trial with placebo or active comparison condition,
· = uncontrolled trial with at least 10 subjects

Medications not recommended for the sole management of insomnia 21, 29
Click for details:

Adverse effects

  • Anticholinergic
  • Sedation
  • Somnolence
  • GI
  • Headache

Notes

  • Relative lack of evidence
  • Significant adverse effects

Adverse effects

  • Anticholinergic
  • Cognitive Impairment
  • Extrapyramidal reactions
  • Hypotension

Notes

  • Lack of evidence or excessive risk of daytime sedation, psychomotor impairment and anticholinergic activity

Adverse effects

  • Anticholinergic
  • Sedation
  • Somnolence
  • Cognitive Impairment

Notes

  • Lack of evidence or excessive risk of daytime sedation, psychomotor impairment and anticholinergic activity

Adverse effects

  • Anticholinergic
  • Sedation
  • Cognitive Impairment
  • Extrapyramidal reactions
  • Weight gain

Notes

  • Lack of evidence
  • Risk of anticholinergic and neurological toxicity (conventional)and metabolic toxicity (atypicals)
  • Possible increased risk of stroke/mortality in patients with behavioural and psychological symptoms of dementia (NNH = 100 in 12 weeks)

Adverse effects

  • Somnolence
  • Impaired function
  • Falls
  • Dependence

Notes

  • Lack of evidence and risk of central nervous system effects

Adverse effects

  • Somnolence
  • GI
  • Weight gain
  • Edema

Notes

  • Lack of evidence

Alternatives to Benzodiazepines for Panic Disorders

The following pages outline many of the non-pharmacological and pharmacological alternative therapy options to benzodiazepines for older adults, along with the level of evidence and adverse effects associated with each therapy. Non-pharmacological alternatives are the preferred treatment for anxiety disorders, insomnia or panic disorder among older adults. As patients age, their bodies respond to medications differently, making them more susceptible to adverse events and drug-drug interactions. If using pharmacological alternatives in older patients, consider patient factors and use the “start low, go slow” approach.

  • Cognitive behavioural therapy as the initial treatment for panic disorder is strongly supported by demonstrated efficacy in numerous randomized controlled trials 4
  • If pharmacotherapy is used, use lower starting and therapeutic doses and a slower dose titration of medication than those used for younger patients 4
Non-pharmacological
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  • Cognitive behavioural therpay

    Level of evidence
    •••

    Notes

    • Demonstrated efficacy in randomized control trials
  • Daily diary

    Level of evidence
    •••

    Notes

    • Allows for monitoring of panic symptoms to gather information about the association between internal stimuli (e.g. emotions) and external stimuli (e.g. substances, particular situations or settings)
  • Patient education

    Level of evidence
    •••

    Notes

    • To reassure the patient that their symptoms are not life-threatening and that panic disorders are common (i.e. they are not alone)
    • Should include general promotion of healthy behaviours (e.g. good nutrition, exercise, good sleep hygiene) as well as decreased used of caffeine, tobacco, alcohol and other potentially deleterious substances
Pharmacological
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  • First-line treatment
    Citalopram, escitalopram, fluoxetine, fluvoxamine and sertraline (SSRIs)

    Level of evidence
    •••

    Adverse effects

    • Insomnia
    • Somnolence
    • Nausea
    • GI
    • Weight gain
    • Sexual dysfunction
    • Qt prolongation
    • Hyponatremia
    • Dry mouth
    • Dizziness
    Additional Information
  • Second-line treament
    Mirtazapine

    Level of evidence
    ••

    Adverse effects

    • Sedation
    • Increased appetite
    • Weight gain
    • Dry mouth
    • Dizziness
    • Edema
    Additional Information
  • Second-line treatment
    Clomipramine and imipramine (TCAs)

    Level of evidence
    •••

    Adverse effects

    • Somnolence
    • Increased appetite
    • Weight gain
    • Suicidal Ideation
    • Confusion
    • Qt prolongation
    • Agitation
    • Dry mouth
    Additional Information
  • Third-line treatment
    Duloxetine (SNRI)

    Level of evidence

    Adverse effects

    • Sleep disturbances
    • Nausea
    • GI
    • Weight gain
    • Dry mouth
    • Dizziness
    • Increased BP
  • Third-line treatment
    Bupropion SR

    Level of evidence

    Adverse effects

    • Insomnia
    • GI
    • Decreased appetite
    • Increased seizure activity
  • Third-line treatment
    Gabapentin

    Level of evidence
    ••

    Adverse effects

    • Somnolence
    • Sedation
    • GI
    • Dizziness
    • Edema
    Additional Information

* Appears in 2019 AGS Beers Criteria® – the Beers Criteria is published by the American Geriatrics Society and is a list of potentially inappropriate medications in older adults 28
Level of evidence:
· · · = meta-analysis or at least 2 randomized controlled trials that included a placebo condition,
· · = at least 1 randomized controlled trial with placebo or active comparison condition,
· = uncontrolled trial with at least 10 subjects

Starting & Continuing Benzodiazepines

Starting a benzodiazepine

For patients starting on a benzodiazepine, use the following information to ensure that benzodiazepines are prescribed safely, considering individual patient factors.

IMPORTANT INFORMATION TO COLLECT BEFORE STARTING A BENZODIAZEPINE
All prescribed and over-the-counter medications patient is currently taking, including supplements, vitamins, and naturopathic treatments
History of previous non-pharmacological and pharmacological alternatives tried • Understand what the patient means by “tried” and consider if the duration “tried” is long enough to evaluate efficacy/side effects • An adequate trial of non-pharmacological and pharmacological alternatives is approximately 6-8 weeks
Substance use history (e.g. alcohol, cannabinoids, caffeine, nicotine)
History of adverse events (e.g. delirium, dementia or cognitive impairment, falls, fractures or motor-vehicle accidents)
Baseline assessment of condition

  • “Start low, go slow”
  • Prescribe the lowest dose necessary to control patient’s symptoms 12, 14, 29
  • Avoid starting long-acting benzodiazepines
  • Limit prescription to 2-4 weeks 29
  • Assess efficacy early and review regularly 29
  • Avoid prescribing benzodiazepines in older adults with a history of delirium, dementia, cognitive impairment, falls, fractures or motor-vehicle accidents 28
  • Put in place safeguards
Benzodiazepine available in Ontario 7, 21, 30, 31
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  • Long-acting
    Chlordiazepoxide

    Formulations

    • Capsule; 5 mg, 10 mg, 25 mg
    • All formulations covered by Ontario Drug Benefit

    Approximate equivalent oral dose(mg)*

    • 10

    Half-life (hours)**

    • 100
  • Long-acting
    Clorazepate

    Formulations

    • Capsule; 3.75 mg, 7.5 mg, 15 mg
    • All formulations covered by Ontario Drug Benefit

    Approximate equivalent oral dose(mg)*

    • 7.5

    Half-life (hours)**

    • 100
  • Long-acting
    Diazepam

    Formulations

    • Tablet; 2 mg^, 5 mg^, 10 mg^
    • All formulations covered by Ontario Drug Benefit

    Approximate equivalent oral dose(mg)*

    • 5

    Half-life (hours)**

    • 100
  • Long-acting
    Flurazepam

    Formulations

    • Capsule; 15 mg, 30 mg
    • Capsule; 15 mg, 30 mg
    • All formulations covered by Ontario Drug Benefit

    Approximate equivalent oral dose(mg)*

    • 5

    Half-life (hours)**

    • 100
  • Intermediate-acting
    Alprazolam

    Formulations

    • Tablet; 0.25 mg^, 0.5 mg^, 1 mg^, 2 mg
    • Only 0.25 mg^, 0.5 mg^ covered by Ontario Drug Benefit

    Approximate equivalent oral dose(mg)*

    • 0.5

    Half-life (hours)**

    • 12-15
  • Intermediate-acting
    Bromazepam

    Formulations

    • Tablet; 1.5 mg^, 3mg^, 1 mg^, 6 mg
    • All formulations covered by Ontario Drug Benefit

    Approximate equivalent oral dose(mg)*

    • 3

    Half-life (hours)**

    • 8-30
  • Intermediate-acting
    Clobazam

    Formulations

    • Tablet; 10 mg^
    • All formulations covered by Ontario Drug Benefit

    Approximate equivalent oral dose(mg)*

    • 10

    Half-life (hours)**

    • 10-46
  • Intermediate-acting
    Clonzepam

    Formulations

    • Tablet; 0.25 mg, 0.5 mg^, 1 mg, 2 mg^
    • Only 0.5 mg^, 2 mg^ Ontario Drug Benefit

    Approximate equivalent oral dose(mg)*

    • 0.25

    Half-life (hours)**

    • 20-80
  • Intermediate-acting
    Lorazapem

    Formulations

    • Tablet; 0.5 mg, 1 mg^, 2 mg^
    • All formulations covered by Ontario Drug Benefit

    Approximate equivalent oral dose(mg)*

    • 1

    Half-life (hours)**

    • 10-20
  • Intermediate-acting
    Nitrazapem

    Formulations

    • Tablet; 5 mg^, 10 mg^
    • All formulations covered by Ontario Drug Benefit

    Approximate equivalent oral dose(mg)*

    • 5

    Half-life (hours)**

    • 16-55
  • Intermediate-acting
    Oxazapem

    Formulations

    • Tablet; 10 mg^, 15 mg^, 30 mg^
    • All formulations covered by Ontario Drug Benefit

    Approximate equivalent oral dose(mg)*

    • 15

    Half-life (hours)**

    • 5-15
  • Intermediate-acting
    Temazapem

    Formulations

    • Capsule; 15 mg, 30 mg
    • All formulations covered by Ontario Drug Benefit

    Approximate equivalent oral dose(mg)*

    • 15

    Half-life (hours)**

    • 10-20
  • Short-acting
    Triazolam

    Formulations

    • Tablet; 0.125 mg^, 0.25 mg^
    • All formulations covered by Ontario Drug Benefit

    Approximate equivalent oral dose(mg)*

    • 0.25

    Half-life (hours)**

    • 1.5-5

^ Scored
* Equivalent to 5mg diazepam
** Parent compound and active metabolite

Continuing a benzodiazepine

For patients starting and continuing on a benzodiazepine, ensure safeguards are put in place to reduce harms and revisit the tapering conversation if/when appropriate.

Safeguards for benzodiazepine prescribing
  • Avoid prescribing any combination of ≥3 central nervous system-active drugs (i.e. antidepressants, antipsychotics, antiepileptics, nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids) 28
  • Use intermittent therapy if appropriate (e.g. limit to 3 nights/week) 14
  • Use limited dispensing 9
  • Collaborate with the patient’s pharmacist regarding packaging options for older adults (e.g. dosette or blister pack), pill counts, home visits as well as patient education on safe storage and proper disposal
  • Set expectations and confirm an exit strategy with the patient
  • Implement treatment agreements
  • Implement adjunctive non-pharmacological therapy (see Alternatives to benzodiazepines for anxiety, insomnia, or panic disorder)
  • Educate the patient about side effects and risk of overdose
  • Educate the patient about avoiding use with alcohol and over-the-counter sedatives (e.g. acetaminophen, codeine)
  • Monitor the patient closely for adverse events, such as cognitive impairment, delirium, falls, fractures and motor vehicle accidents 28
  • Be alert to the development of dependence
    • Tolerance to the effects of benzodiazepines can develop quickly after only 3-6 weeks (i.e. within weeks) and then more of the drug is needed to achieve the same effect12
  • Consider use of urine drug screening if misuse is suspected (note: urine drug screening does not detect all benzodiazepines)
Increased risk: Benzodiazepines and opioids

The concurrent use of benzodiazepines and opioids is associated with an increased risk of adverse reactions due to the depression of the central nervous system exerted by both types of drugs:

  • Increases the risk of cognitive effects, falls, motor vehicle accidents, overdoses and drug-related death 27, 28, 32
  • Risks are increased further when benzodiazepines are taken concurrently with alcohol
  • The expert perspective is that opioids and benzodiazepines should rarely be prescribed together 32
  • For patients who may benefit from both an opioid taper and a benzodiazepine taper, consider completing the opioid taper first or taper the medication that the patient is most willing to taper first 9

Provider Resources

Patient Resources

Psychological Therapy

Independent cognitive behavioural therapy (book, online, and mobile app)

For anxiety disorders and panic disorders

  • Mind Over Mood: A cognitive behavioural therapy hard copy workbook that provides instruction for how to manage anxiety disorders, panic disorder and other mood problems. Cost is $29.64 USD.
  • BounceBack Ontario: Guided self-help program grounded in cognitive behavioural therapy designed to help adults manage symptoms of anxiety (and depression). Involves 6 telephone sessions with trained coaches who lead the patient through a series of workbooks. Cost is free. Patient is contacted within 5 business days of referral to schedule first appointment. Referral or patient self-referral is required.
  • FearFighter — CCBT: A 9-week cognitive behavioural therapy for anxiety and panic disorders mobile app. Provided by Magellan Health Services Inc. Cost is free.
  • Moodgym: A 5-session online cognitive behavioural therapy program for anxiety (and depression). Cost is $39 AUD for 12 month access.
  • Centre for Mindfulness Studies: Provides mindfulness-based cognitive therapy, mindfulness-based stressed reduction, mindful self-compas- sion and specialized mindfulness training to the general public, healthcare providers and social service professionals.
Psychological Therapy

Independent cognitive behavioural therapy (book, online, and mobile app)

For Insomnia

  • Sink into Sleep: A 6-step cognitive behavioural therapy hard copy workbook that provides instruction for how to manage insomnia. Cost is $23.58 CAD.
  • CBT-i Coach: Cognitive behavioural therapy for insomnia mobile app. Provided by the US Department of Veterans Affairs. Cost is free.
  • Restore CBT-I: A 6-week cognitive behavioural therapy for insomnia mobile app. Provided by Magellan Health Services Inc. Cost is free.Re
  • Go! To Sleep: A 6-week cognitive behavioural therapy for insomnia online and mobile app program. Provided by the Cleveland Clinic of Well- ness. Cost is $3.99 USD for app or $40 USD for online.
  • CBT for Insomnia: A 5-session online cognitive behavioural therapy program for insomnia. Cost ranges from $24.95 USD to $49.95 USD.
  • Sleep Training System: A 6-week online cognitive behavioural therapy for insomnia program with money-back guarantee and personalized feedback. Cost is $29.95 USD.
  • Sleepio: Cognitive behavioural therapy for insomnia online and mobile app program. Cost is $300 USD for a 12-month subscription.
Psychological Therapy

In-person cognitive behavioural therapy

Psychological Therapy

Other psychological therapy

Progressive muscle relaxation for anxiety
Physical activity
  • Exercise prescription: Free online/printable patient take-home prescription for aerobic activity or strength training.
  • Tips to get active: Free online/printable physical activity tips for older adults.
  • Seniors Active Living Centres: Map of in-person Seniors Active Living Centres that offer social, cultural, learning and recreational programs for older adults (minimal membership fees).
  • YMCA: List of in-person YMCA locations across Ontario (senior membership approximately $50/month for individuals or $77/month for couples).
Good Sleep Hygiene, sleep Restrictions, Stimulus Control and Progressive Muscle Relaxation for Insomnia
  • Sleepwell: Free online supports for sleep, including sleep hygiene checklist, instructions for sleep restriction instructions, stimulus control and progressive muscle relaxation as well as sleep diaries and sleep calculators.
Daily Diary
  • Sleep Diary: Free online/printable template for patients to use to keep track of their daily sleep patterns.
  • Worry diary: Free online/printable template for patients to use to keep track of their panic symptoms.

References

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    National Institute for Health and Care Excellence (NICE). Generalized anxiety disorder and panic disorder in adults: management. London: NICE; 2011 Jan. 41 p. Report No.:CG113

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    Katzman MA, Bleau P, Blier P, Chokka P, Kjernisted K, Van Ameringen M. Canadian Anxiety Guidelines Initiative Group. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14(Suppl 1):S1.

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    Glass J, Lanctôt KL, Herrmann N, Sproule BA, Busto UE. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ. 2005 Nov;331:1169.

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    American Psychiatric Association (APA). Practice guideline for the treatment of patients with panic disorder [Internet]. 2010 [cited 2019 Jun 5].

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    Alberta College of Family Physicians (ACFP). Benzodiazepines in generalized anxiety disorder: calm your nerves [Internet]. 2015 Apr 27 [cited 2019 Jun 5].

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    Pottie K, Thompson W, Davies S, Grenier J, Sadowski CA, Welch V et al. Deprescribing benzodiazepine receptor agonists: evidence-based clinical practice guideline. Can Fam Physician. 2018 May;64(5):339-51(Eng), e209-24 (Fr).

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    Choosing Wisely Canada. Drowsy without feeling lousy [Internet]. 2017 [updated 2017 Jul; cited 2019 May 28].

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    Sirdfield C, Chipchase SY, Owen S, Siriwardena AN. A systematic review and meta-synthesis of patients’ experiences and perceptions of seeking and using benzodiazepines and z-drugs: towards safer prescribing. Patient. 2017;10(1):1-15.

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    Tannenbaum C. You may be at risk [Internet]. 2014 [cited 2019 May 31].

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    American Psychiatric Association (APA). Diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC: APA; 2013.

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    RxFiles. Geri-RxFiles: assessing medications in older adults. 3rd ed. Saskatoon: Saskatoon City Hospital; 2019.

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    Pfizer ND. Welcome to the Patient Health Questionnaire (PHQ) screeners [Internet]. 2019 [cited 2019 May 31].

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    Vissers FHJA, Knipschild PG, Crebolder HFJM. Is melatonin helpful in stopping the long-term use of hypnotics? A discontinuation trial. Pharm Word Sci. 2007 Dec;29(6):641-646.

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    Voshaar RCO, Gorgels WJMJ, Mol AJJ, Van Balkom AJLM, Van de Lisdonk EH, Breteler MHM et al. Tapering off long-term benzodiazepine use with or without group cognitive-behavioural therapy: three-condition randomised controlled trial. Br J Psychiatry. 2003 Jun;182(6):498-504.

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    Centre for Effective Practice (CEP). Management of chronic insomnia [Internet]. 2017 Jan 16 [cited 2019 May 31].

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    Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Mar;53(4):695-9.

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    Busto UE, Sykora K, Sellers EM. A clinical scale to assess benzodiazepine withdrawal. J Clin Psychopharmacol. 1989 Dec;9(6):412-6.

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    Tyrer P, Murphy S, Riley P. The Benzodiazepine Withdrawal Symptom Questionnaire. J Affect Disord. 1990;19(1):53-61.

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    World Health Organization (WHO). Clinical guidelines for withdrawal management and treatment of drug dependence in closed setting [Internet]. 2009 [cited 2019 Jun 5].

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    Centre for Effective Practice (CEP). Opioid tapering template [Internet]. 2018 Feb [2019 Jun 5].

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    Baandrup L, Ebdrup BH, Rasmussen JØ, Lindschou J, Gluud C, Glenthøj BY. Pharmacological interventions for benzodiazepine discontinuation in chronic benzodiazepine users. Cochrane Database Syst Rev. 2018 Mar 15;3:CD011481.

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    2019 American Geriatrics Society (AGS) Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67:674-694.

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    Toward Optimized Practice (TOP). Diagnosis to management guideline for adult primary insomnia. 2015 [cited 2019 Jun 14].

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    Ontario Ministry of Health and Long-Term Care (MOHLTC). Formulary search [Internet]. 2018 Nov 8 [cited 2019 May 31].

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    Canadian Pharmacists Association (CPhA). Compendium of pharmaceuticals and specialties: Benzodiazepine. 2015 [cited 2019 Jun 14].

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    Busse, J. The 2017 Canadian guideline for opioids for chronic non-cancer pain [Internet]. 2017 [cited 2019 May 31].

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    O’Mahony D, O’Sullivan D, Byrne S, O’Connor MN, Ryan C, Gallagher P. STOPP/START criteria for potentially inappropriate prescribing in older people: version 2. Age Ageing. 2015 Mar;44(2):213-8.

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    Sanofi-Aventis Canada Inc. Product monograph: IvadalTM [Internet]. 2011 [cited 2019 Jun 5].

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    Sanofi-Aventis Canada Inc. Product monograph: Imovane® [Internet]. 2018 [cited 2019 Jun 14].

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    MOHLTC. Exceptional Access Program (EAP) reimbursement criteria for frequently requested drugs [Internet]. 2019 [updated 2019 Mar 1; cited 2019 Jun 5].

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