In an 80‑plus‑year‑old woman with Alzheimer’s disease, recurrent major depressive disorder in partial remission, insomnia, who is taking trazodone 75 mg at bedtime and hydroxyzine (Vistaril) 6.25 mg twice daily, should I add an Exelon (rivastigmine) transdermal patch?

Should You Add Exelon Patch to This Patient's Regimen?

Yes, add the Exelon (rivastigmine) transdermal patch to treat her Alzheimer's disease, but first optimize her insomnia management by discontinuing trazodone and hydroxyzine, then replacing them with low-dose doxepin 3 mg at bedtime. 1, 2

Step 1: Address the Problematic Current Medications

Trazodone 75 mg is explicitly not recommended for insomnia in elderly patients according to the American Academy of Sleep Medicine, which found only minimal improvements (≈10 minutes shorter sleep latency) without any benefit in subjective sleep quality, while adverse events occur in roughly 75% of older patients. 1 The current 75 mg dose is particularly concerning given that trazodone carries risks of orthostatic hypotension, falls, cardiac arrhythmias, and QTc prolongation—all especially dangerous in an 80+ year-old woman. 1, 3

Hydroxyzine (Vistaril) 6.25 mg BID should also be discontinued. The American Academy of Sleep Medicine and American Geriatrics Society explicitly recommend against antihistamines in older adults due to strong anticholinergic effects (confusion, urinary retention, falls, delirium) and tolerance development. 2 Anticholinergic medications are particularly harmful in Alzheimer's disease because they directly oppose the mechanism of cholinesterase inhibitors like rivastigmine. 2

Step 2: Replace with Evidence-Based Insomnia Treatment

Initiate low-dose doxepin 3 mg taken 30 minutes before bedtime as the preferred pharmacologic option for sleep-maintenance insomnia in elderly patients. 1, 2 This dose acts solely as a selective histamine H₁-receptor antagonist, avoiding the anticholinergic and cardiac effects seen with higher doses. 1 Multiple randomized controlled trials in elderly participants reported adverse-event rates indistinguishable from placebo, with no cardiac arrhythmias, QTc prolongation, or orthostatic hypotension. 1

• If sleep does not improve after 1–2 weeks, increase to doxepin 6 mg at bedtime. 1, 2
• Do not exceed 6 mg; higher doses engage tricyclic mechanisms and lose the favorable safety profile. 1
• Monitor for mild somnolence (the only side effect more common than placebo), but no routine cardiac monitoring is required. 1

Cognitive Behavioral Therapy for Insomnia (CBT-I) should be implemented concurrently, including stimulus control (leave bed when unable to sleep), sleep restriction (time in bed = actual sleep + 30 minutes), and maintaining stable bedtimes while avoiding daytime napping. 1, 2

Step 3: Initiate Rivastigmine Transdermal Patch for Alzheimer's Disease

Start rivastigmine transdermal patch 4.6 mg/24 hours applied once daily to clean, dry, intact skin on the upper or lower back. 4 The back is preferred because the patch is less likely to be removed by the patient. 4

Titration schedule:

• Continue the 4.6 mg/24 hours patch for a minimum of 4 weeks if tolerated. 4
• After 4 weeks, increase to 9.5 mg/24 hours patch for another 4 weeks minimum. 4
• For patients with severe Alzheimer's disease (which may apply given her self-talk and mumbling symptoms), the target effective dose is 13.3 mg/24 hours. 4, 5

Application instructions:

• Apply to a different site daily to minimize irritation, avoiding the same location for at least 14 days. 4
• Remove the previous day's patch before applying a new one—only wear one patch at a time. 4
• The patch may be worn during bathing but avoid prolonged exposure to external heat sources. 4

Step 4: Safety Monitoring for Combined Therapy

No direct pharmacokinetic or pharmacodynamic interaction exists between rivastigmine and trazodone (or doxepin), allowing concurrent use. 3 However, additive sedation is a recognized risk; monitor for excessive daytime drowsiness during the first 2–4 weeks. 3

Monitor for orthostatic hypotension and falls by checking orthostatic vital signs at baseline and after each dose adjustment of either medication. 1, 3 Real-world data associate trazodone with approximately 30% fall risk, and rivastigmine may contribute to dizziness. 3

Assess rivastigmine efficacy every 6–12 months through caregiver reports of cognitive function, behavioral symptoms, and activities of daily living. 3

Step 5: Address the Self-Talk and Mumbling

The self-talk and mumbling may represent:

• Progression of Alzheimer's disease requiring treatment with rivastigmine. 4, 6
• Partial remission of major depressive disorder that may improve with rivastigmine's cognitive benefits. 7
• Possible REM sleep behavior disorder (RBD) secondary to dementia, for which the American Academy of Sleep Medicine conditionally suggests transdermal rivastigmine as treatment. 8

Rivastigmine addresses all three possibilities, making it particularly appropriate for this patient. 8, 3

Common Pitfalls to Avoid

• Do not continue trazodone despite its widespread off-label use—explicit guideline recommendations and documented cardiovascular risks contraindicate it in elderly cardiac patients. 1
• Do not use standard adult dosing of any sleep medication; age-adjusted dosing (doxepin 3–6 mg) is essential to reduce fall and cognitive-impairment risk. 1, 2
• Do not fail to implement CBT-I before or alongside pharmacotherapy, which forfeits the more durable benefits of behavioral therapy. 1, 2
• Do not apply multiple rivastigmine patches simultaneously—this is a common error leading to overdose. 4
• Do not interrupt rivastigmine for more than 3 days without restarting at the 4.6 mg dose and re-titrating. 4