What are the considerations for using Diazepam (a benzodiazepine) in elderly patients, particularly those with impaired renal function or a history of dementia?

Diazepam Use in the Elderly: Avoid When Possible

Diazepam should be avoided in elderly patients due to its long half-life, extensive accumulation with chronic use, and substantially increased risks of falls, cognitive impairment, delirium, and mortality—particularly in those with renal impairment or dementia. 1, 2

Primary Recommendation: Avoid Benzodiazepines in Older Adults

• The 2019 American Geriatrics Society Beers Criteria provides a strong recommendation with moderate quality evidence to avoid all benzodiazepines, including diazepam, in older adults due to increased sensitivity and decreased metabolism of long-acting agents. 1

• Benzodiazepines cause cognitive impairment, delirium, falls, fractures, motor vehicle accidents, and increased risk of dependence and withdrawal in elderly patients. 1

• Older adults have greater risk of adverse outcomes including substantial increased mortality, particularly when benzodiazepines are combined with other CNS depressants. 1

Why Diazepam is Particularly Problematic in the Elderly

Pharmacokinetic Issues

• Extensive accumulation of diazepam and its major active metabolite (desmethyldiazepam) occurs following chronic administration in healthy elderly males, with a 2- to 5-fold increase in mean half-life reported. 2

• Diazepam metabolites are substantially excreted by the kidney, making the risk of toxic reactions greater in patients with impaired renal function—a common condition in elderly patients. 2

• In elderly patients with cirrhosis or hepatic insufficiency, clearance decreases while volume of distribution and half-life increase dramatically, with delayed elimination also affecting the active metabolite. 2

Specific Risks in Elderly Populations

• Falls: Benzodiazepine exposure is consistently associated with higher risk of falls in older adults, whether used as monotherapy or in combination with other medications. 3

• Cognitive dysfunction: Short-term adverse effects include confusion and cognitive disorders that regress only slowly after withdrawal, especially in elderly patients. 4

• Potential dementia risk: Case-control studies show benzodiazepine exposure 5-10 years previously was statistically significantly more frequent among elderly patients who developed Alzheimer's disease, though causality remains uncertain. 4

• Delirium: Benzodiazepines substantially increase delirium risk in hospitalized elderly patients. 1

• Respiratory depression: Risk is exponentially increased when combined with opioids or other CNS depressants. 5

Special Considerations for High-Risk Elderly Subgroups

Patients with Renal Impairment

• Because diazepam metabolites are substantially excreted by the kidney, elderly patients with decreased renal function face greater risk of toxic reactions. 2

• Dose selection requires extreme caution, and monitoring renal function may be useful in this population. 2

Patients with Dementia

• Benzodiazepines are contraindicated in elderly patients with dementia due to increased mortality risk and worsening of cognitive symptoms. 1, 5

• The combination can paradoxically worsen delirium rather than improve agitation. 5

• Nonpharmacological interventions should be attempted first for behavioral symptoms. 5

Dosing Algorithm IF Diazepam Cannot Be Avoided

Starting Dose

• Limit dosage to 2 mg to 2.5 mg once or twice daily initially, to be increased gradually only as needed and tolerated, to preclude development of ataxia or oversedation. 2

• This represents the smallest effective amount recommended by the FDA for elderly patients. 2

Duration Limits

• Daily doses must be extremely limited and duration should not exceed 2-3 months even in younger patients—shorter duration is preferable in elderly. 6

• Long-term use should be strongly discouraged because of serious risk of dependence, which is particularly problematic and often unrecognized in the elderly. 7

Preferred Alternatives to Diazepam in the Elderly

For Anxiety

• Consider non-benzodiazepine anxiolytics or brief cognitive therapy with psychoeducation and motivational enhancement. 8

• Melatonin provides effective preoperative anxiolysis with few side effects and may be equally effective to midazolam for anxiety management. 1

For Insomnia or Agitation

• Short-acting benzodiazepines that are not oxidized (lorazepam, temazepam) are preferable to diazepam if a benzodiazepine is absolutely necessary, though avoidance remains the goal. 6

• For agitation in dementia, consider low-dose atypical antipsychotics (quetiapine 25-50 mg at bedtime) only after behavioral interventions have failed. 9

Common Pitfalls to Avoid

• Never use standard adult doses in elderly patients—this significantly increases mortality and morbidity risk. 5, 2

• Avoid long-acting benzodiazepines like diazepam; if a benzodiazepine is unavoidable, use short-acting agents not metabolized through oxidation. 6

• Do not combine with other CNS depressants (opioids, alcohol, antipsychotics) as this exponentially increases adverse outcome risk. 5

• Do not prescribe for patients with COPD, severe pulmonary insufficiency, or sleep apnea due to respiratory depression risk. 5

• Recognize that elderly females with comorbid medical/psychiatric conditions taking multiple medications represent the highest-risk group for benzodiazepine adverse effects. 7

Discontinuation Strategy

• Discontinuation of chronic benzodiazepine use in elderly patients is feasible with adequate psychotherapeutic or pharmacological strategies and can lead to long-term abstinence. 8

• Brief cognitive therapy relying on psychoeducation and motivational enhancement is particularly useful for benzodiazepine discontinuation in this population. 8

• Gradual tapering is essential to avoid withdrawal symptoms, which can be severe in elderly patients with long-term use. 1, 7