What is the safest medication regimen for anxiety, insomnia, and depression in an elderly woman with recent gastrointestinal bleed, heart failure, atrial fibrillation on rivaroxaban and aspirin, hypertension, hyperaldosteronism, osteoporosis, osteoarthritis, and extensive sedating/anticholinergic polypharmacy?

Management of Anxiety, Insomnia, and Depression in an Elderly Woman with Multiple Comorbidities

This patient requires immediate medication optimization—specifically discontinuing Benadryl and addressing alcohol withdrawal—before adding any new psychotropic medications, given her dangerous polypharmacy burden and recent GI bleed. 1

Critical Immediate Actions

1. Discontinue Diphenhydramine (Benadryl) Immediately

• Benadryl 50 mg nightly is explicitly contraindicated in elderly patients per the 2019 AGS Beers Criteria due to strong anticholinergic effects causing confusion, urinary retention, constipation, fall risk, daytime sedation, and delirium 1
• This patient is already on tramadol (anticholinergic), promethazine (anticholinergic), and benzonatate—the cumulative anticholinergic burden significantly increases her fall and delirium risk 1
• Antihistamines develop pharmacologic tolerance within 3-4 days, rendering them ineffective for sustained insomnia management 2

2. Assess and Manage Potential Alcohol Withdrawal

• If she has been drinking regularly and now lacks access, she is at risk for alcohol withdrawal syndrome, which can manifest as anxiety, insomnia, tremors, seizures, and delirium tremens 3
• Her anxiety and insomnia may be withdrawal symptoms rather than primary psychiatric conditions
• If withdrawal is suspected, medical evaluation for benzodiazepine-based withdrawal protocol is required—this is the only appropriate indication for benzodiazepines in this patient 3
• Once withdrawal is complete (typically 5-7 days), reassess psychiatric symptoms before initiating long-term treatment

3. Review and Optimize Existing High-Risk Medications

This patient has dangerous polypharmacy with multiple potentially inappropriate medications:

• Aspirin 81 mg + Xarelto 20 mg: Dual anticoagulation increases GI bleeding risk 1.4-1.6 fold; 70% of rivaroxaban major bleeds occur with concurrent antiplatelet therapy 4, 5, 6
• Tramadol at bedtime: Adds to fall risk, respiratory depression risk (especially with prednisone 20 mg), and anticholinergic burden 1
• Prednisone 20 mg daily: Increases GI bleeding risk with NSAIDs and anticoagulation; contributes to insomnia, anxiety, and osteoporosis 1
• Rivaroxaban dosing: At age >80 with heart failure and hyperaldosteronism, renal function must be verified—35% of rivaroxaban major bleeds involve inappropriate dosing for renal function 4, 7

Deprescribing priorities per ACC 2023 guidelines 1:

• Discontinue aspirin if no recent stent (<12 months) or acute coronary syndrome—rivaroxaban alone provides stroke prevention in atrial fibrillation 1
• Taper prednisone to lowest effective dose or discontinue if possible
• Consider switching tramadol to scheduled acetaminophen (already prescribed as arthritis pain ER 650 mg)

Non-Pharmacologic First-Line Treatment for Insomnia

Cognitive Behavioral Therapy for Insomnia (CBT-I) must be initiated before or alongside any sleep medication 2:

• CBT-I provides superior long-term outcomes compared to pharmacotherapy, with benefits persisting up to 2 years 2
• Core components: stimulus control (leave bed when unable to sleep), sleep restriction (time in bed = actual sleep time + 30 minutes), relaxation techniques (progressive muscle relaxation), cognitive restructuring 2
• Can be delivered via individual therapy, group sessions, telephone-based programs, or web-based modules 2
• Sleep hygiene specifics: limit daytime naps to 15-20 minutes before 3 PM, avoid caffeine after noon, no alcohol in evening, no heavy meals within 3 hours of bedtime 2

Pharmacologic Management of Insomnia

First-Line: Low-Dose Doxepin

Low-dose doxepin 3 mg at bedtime is the safest and most appropriate medication for this patient 2:

• Specifically effective for sleep-maintenance insomnia (the most common pattern in elderly), reducing nocturnal awakenings and early-morning awakenings 2
• At 3-6 mg, doxepin acts solely as a selective histamine H₁-receptor antagonist, avoiding anticholinergic, α-adrenergic, and cardiac-conduction effects seen at higher doses 2
• Cardiovascular safety: Multiple RCTs in elderly patients (including 12-week studies) showed adverse-event rates indistinguishable from placebo, with no cardiac arrhythmias, QTc prolongation, or orthostatic hypotension 2
• Only side effect more frequent than placebo was mild somnolence at 6 mg dose (risk difference +0.04) 2
• Dosing protocol: Start 3 mg 30 minutes before bedtime; if inadequate after 1-2 weeks, increase to 6 mg; reassess at 2 and 4 weeks 2
• Studies up to 12 weeks show sustained benefit without tolerance, dependence, or rebound insomnia 2
• Safe in her cardiac conditions (heart failure, atrial fibrillation) at these low doses 2

Alternative Option: Ramelteon

If sleep-onset difficulty predominates, ramelteon 8 mg is appropriate 2:

• Melatonin-receptor agonist with no known cardiovascular effects 2
• No dependency risk, minimal adverse effects 2
• Particularly useful if circadian rhythm disruption is suspected

Medications That Are ABSOLUTELY CONTRAINDICATED

Benzodiazepines (including lorazepam, temazepam, diazepam) 1, 2, 3:

• AGS Beers Criteria: Strong recommendation against use in elderly due to unacceptable risks of dependency, falls, cognitive impairment, respiratory depression, and increased dementia risk 1, 2
• Directly cause or worsen delirium 3
• This patient has osteoporosis with prior forearm fracture—benzodiazepines increase fracture risk 1
• Only exception: Acute alcohol withdrawal management (short-term, monitored) 3

Trazodone 2:

• American Academy of Sleep Medicine explicitly recommends against trazodone for insomnia in older adults 2
• Provides only 10-minute reduction in sleep latency with no improvement in subjective sleep quality 2
• 75% of older adults experience adverse events (headache 30%, somnolence 23%) 2
• Explicitly contraindicated in cardiac disease: Can provoke arrhythmias (PVCs, ventricular couplets, torsades de pointes), prolongs QT/QTc interval 2
• Causes orthostatic hypotension and syncope—dangerous with her heart failure and hypertension 2

Antihistamines (diphenhydramine, doxylamine) 1, 2:

• Already discussed—strong anticholinergic effects, tolerance within 3-4 days, no proven efficacy 1, 2

Antipsychotics (quetiapine, olanzapine) 2:

• FDA black-box warning: Two-fold increase in mortality in older adults, primarily from cardiovascular or infectious causes 2
• Should never be used for insomnia 2

Z-drugs (zolpidem, eszopiclone, zaleplon) 1:

• AGS Beers Criteria: Avoid in elderly due to increased risk of falls, fractures, cognitive impairment, and motor vehicle accidents 1
• FDA safety warnings about serious injuries from sleep behaviors (sleepwalking, sleep driving) 2
• If absolutely necessary, use only lowest doses (zolpidem ≤5 mg, eszopiclone 1-2 mg, zaleplon 5 mg) for short-term (<4 weeks) 2

Amitriptyline at standard doses 2:

• AGS Beers Criteria: Potentially inappropriate at any dose for insomnia 1
• If unavoidable, maximum 10-20 mg in elderly; higher doses cause severe anticholinergic toxicity (46% constipation rate), cardiac conduction abnormalities, falls 2

Melatonin supplements 2:

• American Academy of Sleep Medicine advises against melatonin (~2 mg) for insomnia in older adults—no clinically meaningful effect demonstrated 2

Management of Depression

Assessment First

• Determine if depression is primary or secondary to:
  • Alcohol use/withdrawal
  • Chronic pain (osteoarthritis, prior fracture)
  • Prednisone use (can cause mood disturbances)
  • Uncontrolled medical conditions (heart failure, hyperaldosteronism)
  • Medication side effects (beta-blockers can cause depression)

Pharmacologic Treatment

If depression persists after addressing above factors, SSRI or SNRI is first-line 3:

• Sertraline 25-50 mg daily is preferred in elderly with cardiac disease:

  • Minimal drug interactions
  • Safe in heart failure
  • Can address both depression and anxiety
  • Start low (25 mg), titrate slowly over 4-6 weeks

• Escitalopram 5-10 mg daily is alternative:

  • Well-tolerated in elderly
  • Fewer drug interactions than citalopram
  • Monitor QTc if dose >10 mg

• Avoid tricyclic antidepressants (amitriptyline, nortriptyline) due to anticholinergic effects, cardiac conduction abnormalities, and orthostatic hypotension in this high-risk patient 1, 2

Non-Pharmacologic Approaches

• Cognitive behavioral therapy for depression
• Physical activity as tolerated (improves sleep, mood, and cardiovascular health)
• Social engagement and support
• Pain management optimization (may improve mood)

Management of Anxiety

Distinguish Anxiety Etiology

• Alcohol withdrawal (if applicable—requires medical management)
• Undertreated pain (osteoarthritis, prior fracture)
• Cardiac symptoms (heart failure, atrial fibrillation with rapid rate)
• Medication-induced (albuterol, prednisone)
• Primary anxiety disorder

Pharmacologic Treatment

If primary anxiety disorder, SSRI/SNRI is first-line 3:

• Same agents as depression (sertraline 25-50 mg or escitalopram 5-10 mg)
• Takes 4-6 weeks for full anxiolytic effect
• Buspirone 5-10 mg twice daily is alternative non-sedating option 3

Short-term bridging (if severe anxiety while awaiting SSRI effect):

• Hydroxyzine 12.5-25 mg is safer than benzodiazepines but still has anticholinergic effects—use cautiously and briefly 1
• Avoid benzodiazepines except for acute alcohol withdrawal 1, 3

Non-Pharmacologic Approaches

• Cognitive behavioral therapy for anxiety
• Relaxation techniques (progressive muscle relaxation, diaphragmatic breathing) 2
• Mindfulness-based stress reduction
• Address underlying medical triggers

Monitoring and Follow-Up

Week 1-2

• Assess for alcohol withdrawal symptoms (if applicable)
• Monitor for adverse effects from Benadryl discontinuation (may have rebound insomnia for 2-3 nights)
• Evaluate sleep with CBT-I implementation
• Check for falls, confusion, or other adverse effects from existing medications

Week 2-4

• Reassess sleep quality and daytime functioning with doxepin 3 mg 2
• If inadequate, increase doxepin to 6 mg 2
• Monitor for mild somnolence, headache, or diarrhea (rare) 2
• Evaluate depression and anxiety symptoms

Week 4-6

• Assess SSRI/SNRI efficacy (if started)
• Consider dose adjustment if needed
• Continue CBT-I reinforcement
• Review medication adherence

Week 12 and Beyond

• Reassess need for continued sleep medication 2
• Consider tapering doxepin after 3-6 months while continuing CBT-I 2
• Monitor for long-term SSRI/SNRI efficacy and tolerability
• Periodic medication review to identify further deprescribing opportunities 1

Common Pitfalls to Avoid

1. Prescribing benzodiazepines for routine anxiety or insomnia instead of recognizing them as deliriogenic and fall-inducing agents contraindicated in elderly 1, 3

2. Continuing Benadryl despite explicit Beers Criteria contraindication and lack of efficacy 1, 2

3. Using trazodone despite guideline recommendations against it and cardiac contraindications in this patient 2

4. Failing to implement CBT-I before or alongside pharmacotherapy, forfeiting more durable behavioral benefits 2

5. Missing alcohol withdrawal as the cause of anxiety and insomnia, leading to inappropriate psychiatric medication instead of medical withdrawal management 3

6. Ignoring polypharmacy burden and continuing to add medications without deprescribing inappropriate agents 1

7. Using standard adult dosing instead of age-adjusted dosing (e.g., doxepin 3-6 mg, not 25-50 mg) 2

8. Continuing dual anticoagulation (aspirin + rivaroxaban) without clear indication, increasing GI bleeding risk in a patient with recent GI bleed 4, 5, 6

9. Not verifying rivaroxaban dose appropriateness for renal function in an 80+ year-old with heart failure 4, 7

10. Combining multiple QTc-prolonging or sedating medications without recognizing cumulative risk 1, 2