Use and misuse of benzodiazepines in the elderly

Contributed by: Jean Triscott, MD, CCFP (COE)¹; Bonnie Dobbs, PhD¹; Frances Carr, MBChB, FRCPC²; Peter Tian, MD, MPH¹; Karen Leung, MD, MSc, CCFP (COE)¹; Jeffrey Chow³, BScPharm, MSc; Jennifer Guzak, RN³

¹Division of Care of the Elderly, Department of Family Medicine, University of Alberta, Edmonton, AB;

²Division of Geriatric Medicine, Department of Medicine, University of Alberta, Edmonton, AB; ³Glenrose Rehabilitation Hospital, Edmonton, AB

Objectives

With respect to medical treatment in the elderly, this article aims to facilitate the understanding of the:

1. Use and misuse of benzodiazepines (BZDs)
2. Risk factors associated with BZD use and misuse
3. Current guidelines around BZD use
4. Strategies for deprescribing BZDs
5. Guidelines for the treatment of insomnia

Case

Ida is a 75-year-old woman living independently in a rented apartment. In the last three months, her family has noticed some cognitive impairment as well as frequent falls. They have also reported that Ida is inconsistent with taking her medication; she spends the majority of the day sleeping so likely has been sleeping through her medication administration time. In the past, Ida has been known to hoard her narcotics instead of taking them as scheduled. Ida’s medical history includes insomnia, right knee osteoarthritis, chronic pain syndrome, depression and anxiety, urinary incontinence and constipation. Her medications include lorazepam 0.5 mg, one tablet at night; clonazepam R 0.5 mg, one tablet twice a day; oxycodone 10 mg, one tablet four times a day; citalopram 20 mg, two tablets every day; and ranitidine 150 mg, one tablet twice a day PRN.

1. Use and misuse of BZDs

The misuse of prescription medication is a growing public health problem in older adults¹. Substance misuse is defined as intentional or unintentional use of a prescribed medication not in accordance with prescribed directions². In the DSM-IV-TR³, misuse of a prescribed medication by the patient is defined as a dose level more than prescribed; longer duration than prescribed; use for purposes other than prescribed; use in conjunction with other medications or alcohol; and skipping doses/hoarding drug. Misuse by the practitioner is defined as prescription for inappropriate indication, prescription for unnecessarily high dose and/or failure to monitor or fully explain appropriate use³.

BZDs and other hypnotic drugs (zolpidem, zopiclone) are some of the most widely used drug classes⁴ and are some of the most frequently prescribed medications for older adults^5,6. Although short-term BZD use may be effective and indicated in some clinical settings, long-term use has very little proven benefit and poses serious risks, particularly in susceptible populations such as the elderly⁷. In a recent systematic review, Maree and colleagues⁸ reported that, in a multi-cohort study of community dwelling seniors in France, BZDs were associated with high risk of mobility limitations with a significant difference in loss of mobility and limitations in instrumental activities of daily living (IADL) for BZD users compared with non-users. BZDs comprise 20%-25% of inappropriate prescriptions in the elderly^9,10 with a reported prevalence of use ranging from 5-32% in community-dwelling older adults^6,11,12. Moreover, although physicians recognize the risks associated with BZD use, almost 50% continue to renew prescriptions, citing patient dependence and benefit as justification for their actions¹³.

2. Risk factors associated with BZD use and misuse

In the older population, BZD use increases the risks of chronic use¹⁴, dementia^15-17, delirium¹⁸, falls and hip fractures^16,19 and motor vehicle crashes^20,21. The risk factors for BZD misuse in the older adult population include increased age^8,14,22,23; female gender^8,14,22; poor self-reported health⁷; chronic pain²²; co-morbidities^22,24; common mental disorders⁷; physical disability or reduced mobility^22,25; IADL limitations²⁵; diagnosis of myocardial infarction⁷; cognitive impairment^2,22; social withdrawal²²; depression²⁴ ; suicide ideation^22,24; and alcohol dependence²⁴. In addition, misuse of BZDs is associated with greater physician visits⁷; use of two or more concomitant medications²⁴; increased emergency department visits^8,26; being hospitalized and becoming very ill²²; and an increased risk of death⁸.

3. Current guidelines around BZD use

The following are the current guidelines regarding BZD use in the elderly:

1. Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults (American Geriatrics Society, 2015)²⁷

• Short- and intermediate-acting BZDs (alprazolam, estazolam, lorazepam, oxazepam, temazepam, triazolam): Older adults have increased sensitivity to BZDs and decreased metabolism of long acting agents. In general, all BZDs increase the risk of cognitive impairment, delirium, falls, fractures, and motor vehicle crashes in older adults²⁷.

2. Screening Tool of Older People's Prescriptions (STOPP) and Screening Tool to Alert to Right Treatment (START) Criteria (British Geriatrics Society, 2015)²⁸

The following prescriptions are potentially inappropriate for use in patients aged 65 years and older:

• BZDs for ≥ four weeks (no indication for longer treatment; risk for prolonged sedation, confusion, impaired balance, falls, and motor vehicle crashes. All BZDs should be withdrawn gradually if taken for more than four weeks as there is a risk of causing BZD withdrawal if stopped abruptly)²⁸ .
• BZDs taken by a patient with acute or chronic respiratory failure (risk of exacerbation of respiratory failure).

3. Choosing Wisely Canada – 5 Things Physicians and Patients Should Question - Geriatrics (Canadian Geriatrics Society, 2017)²⁹.

• Do not use BZDs or other sedative-hypnotics in older adults as first choice for insomnia, agitation or delirium.

4. Strategies for deprescribing BZDs

A systematic review of interventions to deprescribe BZDs and other hypnotics among older people was conducted recently³⁰. Seven studies of BZD and Z-drugs (non-benzodiazepine drugs with effects similar BZDs) withdrawal were identified. BZD discontinuation rates were 64.3% in one study that employed pharmacological substitution with melatonin and 65% in a study that employed general practitioner-targeted intervention. Mixed interventions including patient education and tapering (n=2), pharmacological substitution with psychological support (n=1) and tapering with psychological support (n=1) yielded discontinuation rates between 27% and 80%. Five studies measured clinical outcomes following BZD discontinuation. Most (n=4) observed no difference in prevalence of withdrawal symptoms or sleep quality, while one study reported decline in quality of life in those who continued taking BZDs versus those who discontinued BZDs over eight months. Current evidence indicates that BZD withdrawal is realistic in the older population, but withdrawal rates vary according to the type of intervention. As the benefits and sustainability of withdrawal interventions are unclear, further studies should be conducted for assessment³⁰.

A recent retrospective cohort study compared a medication intervention of orally communicated recommendations (based on the STOPP-START criteria mentioned above) with written medication reviews (control). This was done in a chronic care geriatric facility. In their conclusion, the authors noted that “the effect of an orally communicated medication intervention with the STOPP/START criteria on falls was maintained over time. Direct communication between pharmacists and prescribing physicians is more efficient than written medication reviews for elderly adults and is recommended every six months in geriatric facilities.”³¹.

The College of Physicians and Surgeons of Alberta developed a toolkit for BZD use⁷. Among the recommendations are consideration of alternatives to BZD use and use of gradual tapering (See Figure 1).

Figure 1. Benzodiazepine tapering (Figure redrawn from: College of Physicians and Surgeons of Alberta. Clinical Toolkit. Benzodiazepines: Use and Taper. 2016 Mar). Available here: Alternatives to BZDs for anxiety disorders: Cognitive behaviour therapy, psychotherapy, Selective Serotonin Reuptake Inhibitors (SSRIs), Tricyclic Antidepressants (TCAs), and anxiolytics (buspirone). Alternatives to BZDs for insomnia: Proper sleep hygiene, cognitive behaviour therapy, TCAs (trazodone) and sedating antidepressants (mirtazapine) 7.

The majority of long-term BZD users who are 65 years of age and older report not being concerned about BZD side effects. This is mainly because they have never been alerted to the risks³². In the EMPOWER trial, when provided with evidence-based information about harm in the form of a mailed educational brochure, 27% of chronic BZD users discontinued their use within six months¹³. The EMPOWER brochure consists of an eight-page BZD deprescribing tool embedded with program theories which participants received by mail. A generic version of the EMPOWER tool is available here.

5. Guidelines for the treatment of insomnia

1. The American College of Physicians³³ recommends that:

• All adult patients should receive cognitive behavioral therapy for insomnia (CBT-I) as the initial treatment for chronic insomnia disorder (Grade: Strong recommendation, moderate-quality evidence).
• The ACP recommends that clinicians use a shared decision-making approach, including a discussion of the benefits, harms and costs of short-term use of medications to decide whether to add pharmacological therapy in adults with chronic insomnia disorder in whom CBT-I alone was unsuccessful (Grade: Weak recommendation, low-quality evidence).

2. In older adults, natural melatonin secretion patterns decrease which can lead to changes in circadian rhythm causing insomnia and disrupted sleep cycle. Melatonin may restore a more normal sleep pattern without the problems associated with some other options such as BZDs and non-BZDs hypnotics: dependence, rebound insomnia or withdrawal symptoms. Continued monitoring practices demonstrated no signs of medication withdrawal and a return to normal sleep patterns with melatonin³⁴.

Case Follow-Up

After reviewing the Beers criteria and having a pharmacist review Ida’s medications, the use of lorazepam for insomnia was considered to be inappropriate. Clonazepam, which was used for her anxiety, may have contributed to her symptoms of falls and confusion. Her physician engaged her with the EMPOWER brochure and her BZDs were tapered over two to three weeks. CBT was added as were sleep hygiene practices. Her narcotic load was decreased to hydromorphone 1 mg, one tablet four times a day. Acetaminophen 650 mg one tablet, four times a day was added for pain as well as 5% Diclofenac cream. Ranitidine was discontinued and the citalopram decreased to 20 mg, one tablet daily due to QT interval prolongation on the ECG. Her physician initiated melatonin 2 mg, one tablet at night and increased it to two tablets at night for insomnia. Polyethylene glycol 3350 17 gram dose, one dose a day was added for constipation and she was referred to a continence clinic. She was referred to geriatric psychiatry to manage depression and anxiety. Home care was arranged for the Medication Assistance Program and for morning and evening care. A day program was recommended for social engagement and a social worker became involved with Ida and her family with regard to setting up an Enduring Power of Attorney and Personal Directive. Her physician was involved with maintenance of her medication program and discussion on Goals of Care.

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