What are safe alternative treatments for an elderly patient with insomnia who is currently taking diazepam (benzodiazepine) 5mg and has not responded to trazodone (antidepressant)?

Safe Alternative Treatments for Elderly Patient with Insomnia Refractory to Diazepam and Trazodone

For this elderly patient failing both diazepam and trazodone, I recommend low-dose doxepin (3-6 mg) as the safest and most effective pharmacologic alternative, combined with cognitive behavioral therapy for insomnia (CBT-I) as the foundation of treatment. 1, 2

Immediate Priority: Discontinue Diazepam

• Diazepam must be tapered and discontinued as it is specifically associated with dementia risk in elderly patients, particularly benzodiazepines with half-lives exceeding 24 hours (diazepam, flurazepam, chlordiazepoxide). 1
• Benzodiazepines increase risk of falls, cognitive impairment, and dependence, and should be avoided in elderly patients. 1, 2
• The association with dementia is strongest for higher-dose hypnotics and long-acting benzodiazepines like diazepam. 1

First-Line Treatment: Cognitive Behavioral Therapy for Insomnia (CBT-I)

• CBT-I should be the foundation of treatment as it provides sustained long-term benefits without tolerance issues or adverse effects associated with medications. 1
• CBT-I combines stimulus control, sleep restriction, relaxation therapy, and cognitive restructuring, with benefits better sustained over time compared to pharmacotherapy alone. 1, 2
• Multiple studies demonstrate CBT-I efficacy in older adults, with improvements maintained for up to 2 years. 1
• CBT-I can be delivered through various methods including in-person individual therapy, group therapy, telephone-based modules, or Web-based modules. 1

Recommended Pharmacologic Alternative: Low-Dose Doxepin

Low-dose doxepin (3-6 mg) is the preferred pharmacologic option for this patient based on the following evidence:

• Low-dose doxepin significantly improves sleep maintenance and total sleep time in elderly patients through histamine H1 receptor antagonism. 1, 2
• Doxepin improved mean Insomnia Severity Index scores, sleep onset latency, total sleep time, and wake after sleep onset in older adults with low to moderate strength evidence. 1
• Adverse effects and study withdrawals did not significantly differ from placebo in elderly patients taking low-dose doxepin. 1, 2
• No next-day residual effects or discontinuation problems occur with the 3-6 mg dose. 3

Critical Dosing Distinction

• Only doses of 3-6 mg should be used - higher doses (>6 mg) are listed on the American Geriatrics Society Beers Criteria as potentially inappropriate due to anticholinergic effects. 3
• Start with 3 mg taken 30 minutes before bedtime. 2

Alternative Option: Ramelteon

If doxepin is contraindicated or not tolerated, ramelteon (8 mg) is a reasonable second-line option:

• Ramelteon works through melatonin receptor agonism affecting circadian rhythm, with no abuse potential or significant cognitive/motor impairment. 2
• Ramelteon reduced sleep onset latency by 10 minutes in older adults, though it did not improve total sleep time. 1
• Ramelteon has minimal adverse effects with no differences between ramelteon and placebo in type or frequency of adverse effects. 1
• Suitable for elderly patients with comorbid depression. 2

Why NOT Other Common Options

Melatonin (Not Recommended as Primary Treatment)

• The American Academy of Sleep Medicine provides a weak recommendation AGAINST melatonin for sleep onset or maintenance insomnia due to very low quality evidence. 3
• Melatonin at 2 mg showed only modest sleep latency reduction of approximately 19 minutes compared to placebo. 3
• No clinically significant improvement in sleep quality was found (SMD +0.21; CI: -0.36 to +0.77). 3
• Melatonin is most effective only in elderly patients with documented low melatonin levels or those chronically using benzodiazepines. 3, 4

Z-Drugs (Use with Caution)

• Eszopiclone (1-2 mg) or zolpidem (5 mg) are options but carry significant risks in elderly patients. 1, 2, 5
• Zolpidem is associated with increased risk of falls and fractures (adjusted odds ratio 1.72), cognitive impairment, and 4.28-fold increased risk of falls in hospitalized patients. 2
• Z-drugs are associated with dementia, serious injury, and fractures, which should limit their use. 6
• If used, eszopiclone 1-2 mg is preferred over zolpidem due to lower frequency and severity of adverse effects. 2

Benzodiazepines (Avoid)

• Insufficient evidence exists for temazepam and other benzodiazepine hypnotics in elderly patients. 1
• Benzodiazepines should not be used routinely due to increased risks. 7

Behavioral Interventions to Implement Concurrently

Sleep Restriction-Compression Therapy

• Limit time in bed to correlate closely with actual time sleeping based on 2-week sleep logs. 1
• This consolidates actual sleep time and improves sleep efficiency. 1

Sleep Hygiene Optimization

• Maintain stable bed and wake times. 1, 8
• Avoid daytime napping, especially frequent napping. 1
• Avoid caffeine, nicotine, and alcohol near bedtime. 1, 8
• Ensure the bedroom is not too warm, too noisy, or too bright. 1
• Avoid late evening exercise and late heavy dinners. 1
• Remove television and other stimulating activities from the bedroom. 1

Critical Pitfalls to Avoid

• Do not combine multiple sedative medications as this increases risk of adverse effects. 8
• Do not use antipsychotics like quetiapine as first-line treatment due to metabolic side effects. 8
• Avoid diphenhydramine and other antihistamines in elderly patients due to anticholinergic effects. 6
• Do not continue pharmacotherapy for extended periods - FDA approves hypnotics for short-term use (4-5 weeks), and patients should not continue using drugs for extended periods. 1

Follow-Up and Monitoring

• Regular follow-up every 2-4 weeks initially to assess treatment response and medication tapering progress. 8
• If insomnia does not remit within 7-10 days of treatment, further evaluation is needed to rule out other sleep disorders or psychiatric comorbidities. 1, 8
• Consider sleep study if symptoms persist despite appropriate treatment. 8