How do I discontinue Remeron (mirtazapine) in an elderly male patient with dementia who has had multiple falls while taking it and sertraline 25 mg for depression?

Discontinuing Mirtazapine in an Elderly Male with Dementia and Falls

You should immediately discontinue mirtazapine due to the high fall risk in this elderly patient with dementia, and the lack of evidence supporting antidepressant efficacy for depression in Alzheimer's disease. The combination of sertraline and mirtazapine increases sedation risk, and mirtazapine specifically causes sedation in approximately 23% of patients and is particularly problematic in elderly patients who are more susceptible to orthostatic hypotension 1, 2.

Why Discontinue Mirtazapine

The evidence strongly argues against using either antidepressant in this clinical scenario:

• The HTA-SADD trial, the largest and highest-quality study on this topic, demonstrated that both sertraline and mirtazapine showed no benefit over placebo for depression in Alzheimer's disease at 13 weeks, with adverse reactions occurring in 43% of sertraline patients and 41% of mirtazapine patients versus only 26% with placebo 3.

• Elderly patients are more susceptible to mirtazapine's side effects, particularly sedation, orthostatic hypotension, and hyponatremia 1.

• The 2025 Lancet guidelines on frailty in dementia explicitly recommend reviewing and deprescribing medications that increase fall risk, specifically naming benzodiazepines, antipsychotics, anticholinergics, and opioids as priorities for discontinuation 4.

• Three falls since medication initiation is a clear safety signal requiring immediate medication review 4.

Discontinuation Protocol for Mirtazapine

Taper mirtazapine over 1-2 weeks to minimize withdrawal symptoms:

Week 1:

• Reduce from 15 mg to 7.5 mg daily for 7 days 5
• Monitor for withdrawal symptoms (anxiety, agitation, insomnia, flu-like symptoms)

Week 2:

• Reduce to 3.75 mg (quarter tablet) for 3-4 days, then discontinue 5
• Continue monitoring for withdrawal and fall risk

Note: Mirtazapine can be cross-titrated with sertraline if needed, but given the lack of efficacy data, consider discontinuing both medications 5.

Critical Safety Considerations During Taper

Monitor closely for:

• Fall risk assessment at every contact - all psychotropics increase fall risk in elderly patients 4, 1
• Orthostatic vital signs - check blood pressure sitting and standing to assess orthostatic hypotension risk 1
• Sedation levels - mirtazapine's sedative effects may persist during taper 1
• Withdrawal symptoms - anxiety, agitation, insomnia, or flu-like symptoms 5

Addressing the Underlying Depression

Given the evidence, reconsider the entire treatment approach:

Step 1: Systematic Investigation of Reversible Causes

• Pain assessment - major contributor to behavioral disturbances in patients who cannot verbally communicate discomfort 6
• Infections - check for urinary tract infections and pneumonia 6
• Metabolic disturbances - evaluate for dehydration, constipation, urinary retention 6
• Medication review - identify anticholinergic medications that worsen confusion 6
• Sensory impairments - assess hearing and vision problems that increase confusion and fear 4, 6

Step 2: Non-Pharmacological Interventions (First-Line)

• Environmental modifications - ensure adequate lighting, reduce excessive noise, provide structured daily routines 6
• Communication strategies - use calm tones, simple one-step commands, gentle touch for reassurance 6
• Physical activity - aerobic, strength, balance, and stability training to reduce fall risk 4
• Caregiver education - help caregivers understand that behaviors are symptoms of dementia, not intentional actions 6

Step 3: Reassess Need for Pharmacological Treatment

The evidence suggests antidepressants should NOT be first-line treatment for depression in Alzheimer's disease:

• The HTA-SADD trial showed no clinically meaningful benefit of sertraline or mirtazapine over placebo for depression in Alzheimer's disease 7, 3
• Current practice of using antidepressants as first-line treatment should be reconsidered based on this evidence 3
• If severe depression persists after addressing reversible causes and implementing non-pharmacological interventions, consider psychiatric consultation for alternative approaches 7

Managing Sertraline

Consider tapering sertraline as well, given the lack of efficacy evidence:

• The same HTA-SADD trial showed sertraline provided no benefit over placebo for depression in Alzheimer's disease 3
• If you choose to continue sertraline, monitor for adverse effects including hyponatremia (common in elderly patients) 5
• Sertraline can be tapered by reducing dose by 25-50 mg every 1-2 weeks if discontinuation is pursued 5

Common Pitfalls to Avoid

• Do not continue medications indefinitely without reassessing need - approximately 47% of patients continue receiving psychotropics after discharge without clear indication 6
• Do not add another antidepressant - the evidence does not support antidepressant efficacy in this population 3
• Do not assume falls are unrelated to medications - polypharmacy and inappropriate prescriptions are major risk factors for functional decline 4
• Do not skip the systematic search for reversible causes - pain, infections, and metabolic disturbances are frequently overlooked contributors to behavioral symptoms 6

Falls Risk Management Going Forward

Implement multimodal fall prevention strategies:

• Physical exercise program (aerobic, strength, balance, stability training) 4
• Environmental modifications (remove hazards, install handrails, ensure adequate lighting) 4
• Use of mobility assistance devices as appropriate 4
• Comprehensive gait assessment if resources available 4
• Osteoporosis and fracture risk assessment 4