Managing Benzodiazepine Use in Older Adults

Last Updated: June 30, 2019

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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
  • Is 65 or over
  • 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.
Identify patients 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:

Discuss their use of benzodiazepines

Ask patients what they take the benzodiazepine for:
  • “What concerns did you originally start the benzodiazepine for?”10
  • “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:
    • 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”11
  • “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):
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Discontinuing Benzodiazepines

Important information to collect before discontinuing benzodiazepines

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

If taking a benzodiazepine is no longer appropriate for a patient, then use the following steps to help them taper off of the
medication or to a lower dose.

Step 1: Plan the taper

Engage patients
  • In developing a clear plan for tapering, incorporating goals and preferences regarding benzodiazepine use.7
  • 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–acting benzodiazepines vs. short-acting benzodiazepines) for a tapering schedule.7
  • 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 benzodiazepinestaper by no more than diazepam 5mg or clonazepam 0.25mg equivalent/week.21
Alternative rates for tapering
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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 weeks14
  • 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 week14
  • 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 instruct the pharmacist to dispense daily, weekly or every 2 weeks depending on the dose and patient reliability.21

Step 2: Consider adjunctive therapy

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 Provider and Patients Resources)7.
  • The use of pharmacological adjunctive agents has limited evidence to support success.

Step 3. Initiate and monitor7,12

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 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.21
Talking points
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Talking Points

  • “There are more effective treatments than benzodiazepines for your [anxiety/ insomnia/panic disorder].” 2, 17
  • “Many people have successfully stopped taking their benzodiazepine — the majority of people can stop through tapering.” 7, 18

Ensure patients (and caregivers) are aware of withdrawal symptoms7

  • “You may experience a night or two of worse sleep.”9
  • “To reduce your risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents, you might need to get through a few days/weeks of mild withdrawal symptoms.”9
Monitor for expected benefits and withdrawal symptoms7, 12

Expected benefits:

  • Less daytime sedation
  • Improved cognition. Use validated assessment tools such as, the Montreal Cognitive Assessment.22
  • 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. Use a validated assessment tool such as, the Insomnia Severity Index.16
  • 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 disorders7

Manage withdrawal symptom(s)
  • 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
  • Currently, no medications are recommended or approved for the management of benzodiazepine withdrawal after long-term use.27
Pharmacotherapy symptom management

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.

  • Oxybutynin* 2.5–5mg bid prn (short-term use)
  • Ensure patient is well-hydrated

 

* 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 adults28

  • 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 adults28

  • Dimenhydrinate* 25–50mg q4h prn •
  • Prochlorperazine* 5–10mg q6h prn
  • Haloperidol* 0.5–1mg q12h prn
  • Metoclopramide* 10mg q4–6h prn

* 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 adults28

Starting Benzodiazepines

Important information to collect before starting benzodiazepines

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
  • 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

Tips for safe benzodiazpine prescribing

  • “Start low, go slow”
  • Prescribe the lowest dose necessary to control patient’s symptoms12, 14, 29
  • Avoid starting long-acting benzodiazepinesLimit prescription to 2-4 weeks29
  • Assess efficacy early and review regularly29
  • Avoid prescribing benzodiazepines in older adults with a history of delirium, dementia, cognitive impairment, falls, fractures or motor-vehicle accidents28

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 limited dispensing9 and intermittent therapy, if appropriate (e.g. limit to 3 nights/week).14

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 – a sample benzodiazepine treatment agreement is available from the College of Physicians and Surgeons of Alberta. 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).

Implement adjunctive non-pharmacological therapy (see Alternatives to benzodiazepines for anxiety, insomnia, or panic disorder).

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 effect.12 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

Benzodiazepine available in Ontario7, 21, 30, 31

Scroll (left-right) for details
  • Long-acting
    Chlordiazepoxide

    Covered by Ontario Drug Benefit30

    Formulations

    • Capsule: 5 mg, 10 mg, 25 mg

    Approximate equivalent to 5mg diazepam oral dose

    • 10 mg

    Half-life (hours)**

    • 100
  • Long-acting
    Clorazepate

    Covered by Ontario Drug Benefit30

    Formulations

    • Capsule: 3.75 mg, 7.5 mg, 15 mg

    Approximate equivalent to 5mg diazepam oral dose

    • 7.5 mg

    Half-life (hours)**

    • 100
  • Long-acting
    Diazepam

    Covered by Ontario Drug Benefit30

    Formulations

    • Tablet: 2 mg^, 5 mg^, 10 mg^

    Approximate equivalent to 5mg diazepam oral dose

    • 5 mg

    Half-life (hours)**

    • 100
  • Long-acting
    Flurazepam

    Covered by Ontario Drug Benefit30

    Formulations

    • Capsule: 15 mg, 30 mg

    Approximate equivalent to 5mg diazepam oral dose

    • 15 mg

    Half-life (hours)**

    • 100
  • Intermediate-acting
    Alprazolam

    Only 0.25 mg, 0.5 mg covered by Ontario Drug Benefit30

    Formulations

    • Tablet: 0.25 mg^, 0.5 mg^, 1 mg^, 2 mg

    Approximate equivalent to 5mg diazepam oral dose

    • 0.5 mg

    Half-life (hours)**

    • 12-15
  • Intermediate-acting
    Bromazepam

    Covered by Ontario Drug Benefit30

    Formulations

    • Tablet: 1.5 mg^, 3mg^, 6 mg^

    Approximate equivalent to 5mg diazepam oral dose

    • 3 mg

    Half-life (hours)**

    • 8-30
  • Intermediate-acting
    Clobazam

    Covered by Ontario Drug Benefit30

    Formulations

    • Tablet: 10 mg^

    Approximate equivalent to 5mg diazepam oral dose

    • 10 mg

    Half-life (hours)**

    • 10-46
  • Intermediate-acting
    Clonzepam

    Only 0.5 mg^, 2 mg^ covered by Ontario Drug Benefit

    Formulations

    • Tablet: 0.25 mg, 0.5 mg^, 1 mg, 2 mg^

    Approximate equivalent to 5mg diazepam oral dose

    • 0.25 mg

    Half-life (hours)**

    • 20-80
  • Intermediate-acting
    Lorazapem

    Covered by Ontario Drug Benefit30

    Formulations

    • Tablet: 0.5 mg, 1 mg^, 2 mg^

    Approximate equivalent to 5mg diazepam oral dose

    • 1 mg

    Half-life (hours)**

    • 10-20
  • Intermediate-acting
    Nitrazapem

    Covered by Ontario Drug Benefit30

    Formulations

    • Tablet: 5 mg^, 10 mg^

    Approximate equivalent to 5mg diazepam oral dose

    • 5 mg

    Half-life (hours)**

    • 16-55
  • Intermediate-acting
    Oxazapem

    Covered by Ontario Drug Benefit30

    Formulations

    • Tablet: 10 mg^, 15 mg^, 30 mg^

    Approximate equivalent to 5mg diazepam oral dose

    • 15 mg

    Half-life (hours)**

    • 5-15
  • Intermediate-acting
    Temazapem

    Covered by Ontario Drug Benefit30

    Formulations

    • Capsule: 15 mg, 30 mg

    Approximate equivalent to 5mg diazepam oral dose

    • 15 mg

    Half-life (hours)**

    • 10-20
  • Short-acting
    Triazolam

    Covered by Ontario Drug Benefit30

    Formulations

    • Tablet: 0.125 mg^, 0.25 mg^

    Approximate equivalent to 5mg diazepam oral dose

    • 0.25 mg

    Half-life (hours)**

    • 1.5-5

^ Scored
** Parent compound and active metabolite

Continuing Benzodiazepines

For patients 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 limited dispensing9 and intermittent therapy, if appropriate (e.g. limit to 3 nights/week).14

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 – a sample benzodiazepine treatment agreement is available from the College of Physicians and Surgeons of Alberta. 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).

Implement adjunctive non-pharmacological therapy (see Alternatives to benzodiazepines for anxiety, insomnia, or panic disorders).

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 effect.12 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

Benzodiazepine available in Ontario7, 21, 30, 31

Scroll (left-right) for details
  • Long-acting
    Chlordiazepoxide

    Covered by Ontario Drug Benefit30

    Formulations

    • Capsule: 5 mg, 10 mg, 25 mg

    Approximate equivalent to 5mg diazepam oral dose

    • 10 mg

    Half-life (hours)**

    • 100
  • Long-acting
    Clorazepate

    Covered by Ontario Drug Benefit30

    Formulations

    • Capsule: 3.75 mg, 7.5 mg, 15 mg

    Approximate equivalent to 5mg diazepam oral dose

    • 7.5 mg

    Half-life (hours)**

    • 100
  • Long-acting
    Diazepam

    Covered by Ontario Drug Benefit30

    Formulations

    • Tablet: 2 mg^, 5 mg^, 10 mg^

    Approximate equivalent to 5mg diazepam oral dose

    • 5 mg

    Half-life (hours)**

    • 100
  • Long-acting
    Flurazepam

    Covered by Ontario Drug Benefit30

    Formulations

    • Capsule: 15 mg, 30 mg

    Approximate equivalent to 5mg diazepam oral dose

    • 15 mg

    Half-life (hours)**

    • 100
  • Intermediate-acting
    Alprazolam

    Only 0.25 mg, 0.5 mg covered by Ontario Drug Benefit30

    Formulations

    • Tablet: 0.25 mg^, 0.5 mg^, 1 mg^, 2 mg

    Approximate equivalent to 5mg diazepam oral dose

    • 0.5 mg

    Half-life (hours)**

    • 12-15
  • Intermediate-acting
    Bromazepam

    Covered by Ontario Drug Benefit30

    Formulations

    • Tablet: 1.5 mg^, 3mg^, 6 mg^

    Approximate equivalent to 5mg diazepam oral dose

    • 3 mg

    Half-life (hours)**

    • 8-30
  • Intermediate-acting
    Clobazam

    Covered by Ontario Drug Benefit30

    Formulations

    • Tablet: 10 mg^

    Approximate equivalent to 5mg diazepam oral dose

    • 10 mg

    Half-life (hours)**

    • 10-46
  • Intermediate-acting
    Clonzepam

    Only 0.5 mg^, 2 mg^ covered by Ontario Drug Benefit

    Formulations

    • Tablet: 0.25 mg, 0.5 mg^, 1 mg, 2 mg^

    Approximate equivalent to 5mg diazepam oral dose

    • 0.25 mg

    Half-life (hours)**

    • 20-80
  • Intermediate-acting
    Lorazapem

    Covered by Ontario Drug Benefit30

    Formulations

    • Tablet: 0.5 mg, 1 mg^, 2 mg^

    Approximate equivalent to 5mg diazepam oral dose

    • 1 mg

    Half-life (hours)**

    • 10-20
  • Intermediate-acting
    Nitrazapem

    Covered by Ontario Drug Benefit30

    Formulations

    • Tablet: 5 mg^, 10 mg^

    Approximate equivalent to 5mg diazepam oral dose

    • 5 mg

    Half-life (hours)**

    • 16-55
  • Intermediate-acting
    Oxazapem

    Covered by Ontario Drug Benefit30

    Formulations

    • Tablet: 10 mg^, 15 mg^, 30 mg^

    Approximate equivalent to 5mg diazepam oral dose

    • 15 mg

    Half-life (hours)**

    • 5-15
  • Intermediate-acting
    Temazapem

    Covered by Ontario Drug Benefit30

    Formulations

    • Capsule: 15 mg, 30 mg

    Approximate equivalent to 5mg diazepam oral dose

    • 15 mg

    Half-life (hours)**

    • 10-20
  • Short-acting
    Triazolam

    Covered by Ontario Drug Benefit30

    Formulations

    • Tablet: 0.125 mg^, 0.25 mg^

    Approximate equivalent to 5mg diazepam oral dose

    • 0.25 mg

    Half-life (hours)**

    • 1.5-5

^ Scored
** Parent compound and active metabolite

Alternatives to Benzodiazepines for Anxiety

The following 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 options1,2

Non-pharmacological alternatives are the preferred treatment for anxiety disorders, insomnia or panic disorder among older adults.

Scroll (left-right) for details
  • 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 options

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.

Scroll (left-right) for details
  • First-line treatment (SSRIs)
    Escitalopram and Sertraline

    Level of evidence • • •

    Adverse effects

    • Insomnia
    • Somnolence
    • Sedation
    • Nausea
    • GI
    • Sexual Dysfunction
    • Qt prolongation
    • Dizziness
    • Dry mouth
    • Hyponatremia

    Additional information

    • SSRI appears as a class in 2019 AGS Beers Criteria®*
  • First-line treatment (SNRIs)
    Duloxetine and Venlafaxine ER

    Level of evidence • • •

    Adverse effects

    • Insomnia
    • Sleep disturbances
    • Sedation
    • Nausea
    • GI
    • Decreased appetite
    • Increased BP
    • Dizziness
    • Hyponatremia

    Additional information

    • SNRI appears as a class in 2019 AGS Beers Criteria®*
  • First-line treatment
    Pregabalin

    Level of evidence • • •

    Adverse effects

    • Sedation
    • Nausea
    • GI
    • Increased appetite and weight
    • Dizziness
    • Dry mouth

    Additional information

    • Pregabalin has the most robust data in older patients that demonstrates significant improvements and good tolerability
  • Second-line treatment
    Bupropion SR/XL

    Level of evidence • • 

    Adverse effects

    • Insomnia
    • GI
    • Decreased appetite
    • Increased seizure activity
  • Third-line treatment (SSRIs)
    Citalopram

    Level of evidence •

    Adverse effects

    • Insomnia
    • Sleep disturbances
    • Somnolence
    • Sedation
    • Nausea
    • GI
    • Sexual dysfunction
    • Qt prolongation
    • Dizziness
    • Dry mouth
    • Hyponatremia

    Additional information

    • May increase QT (doses >40mg/day)
    • SSRI appears as a class in 2019 AGS Beers Criteria®*
  • Third-line treatment
    Trazodone

    Level of evidence • •

    Adverse effects

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

    Level of evidence •

    Adverse effects

    • Sedation
    • Increased appetite & weight
    • Dizziness
    • Dry mouth
  • Third-line treatment (SNRI)
    Fluoxetine

    Level of evidence •

    Adverse effects

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

    Additional information

    • SNRI appears as a class in 2019 AGS Beers Criteria®*
    • Long half-life (5-week washout)

Notes: BP= blood pressure, ER= extended release, CR= controlled release, GI= gastrointestinal, SNRIs= serotonin and norepinephrine reuptake inhibitors, SR= sustained release, SSRIs= selective serotonin reuptake inhibitors, XL= extra-long /large

* 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

Alternatives to Benzodiazepines for Insomnia

The following outlines 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 options

Non-pharmacological alternatives are the preferred treatment for anxiety disorders, insomnia or panic disorder among older adults.

Scroll (left-right) for details
  • Cognitive behavioural therapy

    Level of evidence • • to • • •

    Notes

    • Cognitive behavioural therapy for insomnia is more effective than pharmacological therapy for the short- and long-term management of insomnia in older adults.17
    • 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

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

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

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

Discontinuing Z-drugs14

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 end7

Educate the patient that some sleep difficulty should be expected but that it should resolve within a week.

Pharmacological options

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.

There are no medications for primary or chronic insomnia in older adults that are proven to be safe and effective.7

Scroll (left-right) for details
  • Z-drug
    Zopiclone

    Level of evidence • to • •

    Covered by Exceptional Access Program39

    Formulations

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

    Notes

    • Indicated for insomnia but avoid in older adults28
    • Improves sleep onset latency (~19 min), total sleep time (~45 min), wake after sleep onset (~11 min)
    • Risk of physical tolerance and dependence
  • Z-drug
    Zolpidem

    Level of evidence • to • •

    Possibly covered by Exceptional Access Program40

    Formulations

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

    Notes

    • Indicated for insomnia but avoid in older adults28
    • 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
  • Tricyclic antidepressant
    Doxepin

    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

Notes: TCA= tricyclic antidepressant, Z-drugs= non-benzodiazepine benzodiazepine receptor agonist hypnotics

• the Beers Criteria is published by the American Geriatrics Society and is a list of potentially inappropriate medications in older adults28
^ Scored

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

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
  • 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 outlines 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 options

Non-pharmacological alternatives are the preferred treatment for anxiety disorders, insomnia or panic disorder among older adults.

Scroll (left-right) for details
  • Cognitive behavioural therpay

    Level of evidence • • •

    Notes

    • Cognitive behavioural therapy as the initial treatment for panic disorder is strongly supported by demonstrated efficacy in numerous randomized controlled trials 4
  • 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

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 options

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.

If pharmacotherapy is used, use lower starting and therapeutic doses and a slower dose titration of medication than those used for younger patients.4

Scroll (left-right) for details
  • 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

    Notes

    • SSRI appears as a class in 2019 AGS Beers Criteria®*
    • Few drug interactions
  • Second-line treament
    Mirtazapine

    Level of evidence • •

    Adverse effects

    • Sedation
    • Increased appetite
    • Weight gain
    • Dry mouth
    • Dizziness
    • Edema

    Notes

    • SSRI appears as a class in 2019 AGS Beers Criteria®*

     

  • 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

    Notes

    • Appears in 2019 AGS Beers Criteria®*
    • Caution due to anticholinergic and cardiovascular side effects
  • Third-line treatment
    Duloxetine (SNRI)

    Level of evidence •

    Adverse effects

    • Sleep disturbances
    • Nausea
    • GI
    • Decreased appetite
    • 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

    Notes

    • Appears in 2019 AGS Beers Criteria®*

Notes: BP= blood pressure, GI= gastrointestinal, SNRIs= serotonin and norepinephrine reuptake inhibitors, SR= sustained release, SSRIs= selective serotonin reuptake inhibitors, TCAs= tricyclic antidepressants

* 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

Provider and Patient Resources

For providers

Decision support tools and resources

For patients

For patients with anxiety disorders and/or panic disorders

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

  • 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.

Progressive muscle relaxation for anxiety

Daily Diary

  • Worry diary: Free online/printable template for patients to use to keep track of their panic symptoms.
For patients with insomnia

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

  • 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.

Good Sleep Hygiene, sleep Restrictions, Stimulus Control and Progressive Muscle Relaxation

  • 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.
For patients: general psychological therapy

In-person cognitive behavioural therapy

Other psychological therapy

For patients: physical activity

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: Seniors Active Living Centres locations
  • YMCA: List of in-person YMCA locations across Ontario (senior membership approximately $50/month for individuals or $77/month for couples).

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