What are the considerations for using Wellbutrin (bupropion), Buspar (buspirone), and Remeron (mirtazapine) in a dementia patient with sundowning?

Wellbutrin, Buspar, and Remeron in Dementia with Sundowning

Direct Recommendation

None of these three medications—Wellbutrin (bupropion), Buspar (buspirone), or Remeron (mirtazapine)—are appropriate first-line treatments for sundowning in dementia patients, and their use should be avoided or minimized in favor of non-pharmacological interventions and evidence-based alternatives. 1, 2

Specific Medication Concerns

Wellbutrin (Bupropion)

• Bupropion is not recommended for sundowning or behavioral symptoms in dementia as it lacks evidence for efficacy in this population and may increase agitation and confusion. 3, 4
• This medication can lower seizure threshold, which is particularly concerning in elderly dementia patients who already have increased seizure risk. 5
• No clinical trials support its use for sundowning or neuropsychiatric symptoms of dementia. 3, 4

Buspar (Buspirone)

• Buspirone has no established role in treating sundowning or behavioral symptoms of dementia and lacks evidence from controlled trials in this population. 3, 4
• While it may be used for anxiety in other contexts, there is no specific evidence supporting its efficacy for the temporal pattern of symptoms characteristic of sundowning. 4
• The medication contributes to polypharmacy burden without substantiated benefit in dementia patients. 5

Remeron (Mirtazapine)

• Mirtazapine may be considered only if comorbid depression is present, as it is among the safer antidepressants for dementia patients due to fewer drug interactions. 2
• However, mirtazapine should not be used specifically for sundowning or sleep disturbances alone, as sleep-promoting medications are strongly discouraged in elderly dementia patients due to increased risks of falls, cognitive decline, and daytime hypersomnolence. 1
• If depression is documented and severe enough to warrant treatment, mirtazapine is a reasonable option among antidepressants, but SSRIs (citalopram, escitalopram, sertraline) are generally preferred first-line agents. 2
• The sedating properties of mirtazapine do not justify its use for sleep problems in dementia, as the risks outweigh benefits. 1

Evidence-Based Treatment Algorithm for Sundowning

Step 1: Non-Pharmacological Interventions (Mandatory First-Line)

• Implement morning bright light therapy at 2,500-5,000 lux for 1-2 hours daily between 9:00-11:00 AM, positioned approximately 1 meter from the patient, to regulate circadian rhythms and decrease evening agitation. 1
• Maximize daytime sunlight exposure (at least 30 minutes daily) while reducing nighttime light and noise exposure. 1
• Increase physical and social activities during daytime hours to consolidate nighttime sleep and reduce evening restlessness. 1, 3
• Establish a structured bedtime routine to provide temporal cues and create a sleep-conducive environment. 1
• Remove potentially dangerous objects from the bedroom for safety during periods of confusion and agitation. 1

Step 2: Evaluate for Underlying Contributors

• Assess for pain, urinary retention, constipation, and other medical conditions that may manifest as behavioral symptoms in dementia patients. 2
• Review all current medications for anticholinergic properties and discontinue or substitute alternatives, as anticholinergic burden worsens cognition and behavioral symptoms. 1, 2
• Evaluate for hearing loss, which is associated with sundowning and should be addressed with hearing aids if present. 6

Step 3: Consider Evidence-Based Pharmacological Options (If Non-Pharmacological Measures Fail)

For patients already on dementia medications:

• Ensure the patient is on memantine if appropriate, as memantine use is associated with reduced sundowning (OR 0.20; 95% CI 0.05-0.74). 6
• Consider cholinesterase inhibitors (donepezil, rivastigmine, galantamine) if not already prescribed, as they have shown benefit in reducing evening agitation and improving circadian rhythmicity. 3, 7

For comorbid depression:

• If major depression is documented, initiate an SSRI (citalopram, escitalopram, or sertraline) as first-line treatment, as serotonergic antidepressants reduce overall neuropsychiatric symptoms including agitation. 2
• Mirtazapine may be used as an alternative antidepressant if SSRIs are contraindicated or poorly tolerated, but only for documented depression, not for sleep or sundowning alone. 2

For dangerous agitation or psychosis:

• Antipsychotics should only be used for dangerous agitation or psychosis that poses risk to self or others, after comprehensive assessment and discussion of risks with family. 5
• If antipsychotics are necessary, use the lowest effective dose for the shortest duration (typically 3 months maximum), with regular attempts at tapering. 5
• Antipsychotics carry an FDA black box warning for increased mortality risk in dementia patients and should never be used for mild behavioral symptoms. 5

Critical Medications to Avoid

• Benzodiazepines are absolutely contraindicated due to high risk of falls, confusion, worsening cognitive impairment, and paradoxical agitation. 5, 1
• Sleep-promoting medications (hypnotics, sedatives) are strongly discouraged as they increase falls, cognitive decline, and daytime hypersomnolence without meaningful benefit. 1
• Melatonin is not recommended as clinical trials have failed to demonstrate significant improvements in sleep or behavioral symptoms in dementia patients. 1
• Anticholinergic medications should be minimized or eliminated, as they worsen cognition and behavioral symptoms. 1, 2

Common Pitfalls to Avoid

• Do not treat sundowning as a sleep disorder requiring sedation—this approach increases harm without addressing the underlying circadian rhythm dysfunction. 1, 3
• Do not prescribe medications for individual symptoms (insomnia, irritability, anxiety) in isolation—address the comprehensive syndrome and underlying causes. 1, 2
• Do not continue ineffective medications—if behavioral symptoms persist or worsen after 3-4 weeks of treatment, discontinue the medication rather than adding more agents. 2
• Do not overlook polypharmacy as a contributor—medication burden itself worsens outcomes in dementia patients. 5

Deprescribing Considerations

If the patient is already taking these medications:

• Wellbutrin and Buspar should be tapered and discontinued as they lack evidence for benefit in dementia with sundowning and contribute to polypharmacy burden. 5
• Remeron should be continued only if treating documented major depression with demonstrated benefit; otherwise, taper over 2-4 weeks while implementing non-pharmacological interventions. 5, 2
• Monitor closely for withdrawal symptoms and worsening behaviors during tapering, but recognize that discontinuation often does not worsen behavioral symptoms and may improve overall function. 5