What is the role of Remeron (mirtazapine) in treating dementia?

Mirtazapine (Remeron) Should Not Be Used for Treating Dementia-Related Symptoms

Based on the highest quality recent evidence, mirtazapine is not recommended for treating agitation in dementia and should be reconsidered as first-line treatment for depression in Alzheimer's disease due to lack of efficacy and potential safety concerns, including a signal for increased mortality. 1, 2

Evidence for Agitation in Dementia

The most definitive evidence comes from the 2021 SYMBAD trial, a large randomized controlled trial specifically examining mirtazapine for agitation in dementia 1:

• No clinical benefit: Mirtazapine (45 mg) showed no significant reduction in agitation scores compared to placebo at 12 weeks (adjusted mean difference -1.74,95% CI -7.17 to 3.69; p=0.53) 1
• Mortality signal: Seven deaths occurred in the mirtazapine group versus one in placebo by week 16, a difference of marginal statistical significance (p=0.065) 1
• Similar adverse event rates: 66% of mirtazapine patients experienced adverse events compared to 64% on placebo 1

The 2023 follow-up analysis confirmed these findings and added economic data showing mirtazapine increased unpaid caregiver costs by £1,120 without clinical benefit 3. The data do not support using mirtazapine as a treatment for agitation in dementia. 1

Evidence for Depression in Dementia

For depression in Alzheimer's disease, the 2011 HTA-SADD trial provides definitive evidence 2:

• No efficacy: At 13 weeks, mirtazapine showed no difference from placebo in reducing depression scores (mean difference 0.01,95% CI -1.37 to 1.38; p=0.99) 2
• Increased adverse events: 41% of mirtazapine patients had adverse reactions versus 26% on placebo (p=0.031) 2
• Equal mortality: Five deaths occurred in each group by 39 weeks 2

The current practice of using mirtazapine for first-line treatment of depression in Alzheimer's disease should be reconsidered. 2

When Mirtazapine Might Still Be Considered

Despite the negative primary evidence, mirtazapine may have a limited role in highly specific clinical scenarios 4:

• Significant weight loss or anorexia where the weight gain side effect (occurring in 10% of patients) would be therapeutically beneficial in elderly dementia patients 5, 4
• Severe insomnia requiring a sedating agent, as sedation occurs in 23% of patients 5, 4
• Concern about drug interactions, as mirtazapine has fewer interactions than other antidepressants in polypharmacy situations 4

Critical Safety Considerations

When mirtazapine is used despite the evidence against it, monitor closely for 5, 4:

• Excessive sedation (23% incidence), particularly problematic in elderly dementia patients 5
• Falls and orthostatic hypotension, as elderly patients are especially susceptible 5, 4
• Hyponatremia risk in elderly populations 5, 4
• Weight gain (10% incidence), though this may be beneficial in some cases 5

Start at low doses and titrate slowly in elderly dementia patients to minimize these risks 4.

Alternative Approaches

Current guidelines emphasize 6:

• Non-pharmacological interventions should take precedence over pharmacotherapy for behavioral and psychological symptoms of dementia 6
• Cognitive interventions (reality orientation, cognitive stimulation, reminiscence therapy) may be considered 6
• Antipsychotics should not be first-line for behavioral symptoms; use only for clear and imminent risk of harm with severe symptoms, preferably short-term and in consultation with specialists 6

Clinical Bottom Line

The weight of high-quality evidence from large randomized controlled trials demonstrates that mirtazapine lacks efficacy for both agitation and depression in dementia, while carrying risks of adverse events and a potential mortality signal 1, 3, 2. The one small positive pilot study from 2008 with only 13 completers is vastly outweighed by subsequent definitive trials 7, 1, 2. Mirtazapine should not be routinely prescribed for dementia-related symptoms, and its use should be restricted to exceptional cases where specific side effects (weight gain, sedation) would provide therapeutic benefit that outweighs the lack of evidence for primary efficacy 4.