Starting Dose of Mirtazapine in Elderly Patients
Start mirtazapine at 7.5 mg once daily at bedtime in elderly patients, which is half the standard starting dose, then titrate cautiously based on response and tolerability. 1
Rationale for Dose Reduction in Elderly
While the FDA-approved starting dose for adults is 15 mg once daily at bedtime 1, elderly patients require special consideration due to:
- Increased sensitivity to sedation and neuropsychiatric effects - The elderly are particularly vulnerable to mirtazapine's sedative properties and perceptual abnormalities, requiring close monitoring 2
- Altered pharmacokinetics - Mirtazapine has an elimination half-life of approximately 20-40 hours, and clearance may be reduced in elderly patients due to age-related decline in hepatic and renal function 3, 4, 5
- Higher steady-state concentrations - Elderly patients reach steady-state in 6 days compared to 4 days in younger adults, with potentially higher drug concentrations 6
Titration Strategy
After starting at 7.5 mg:
- Maintain initial dose for at least 1-2 weeks to allow adequate time for evaluation of response and tolerability 1
- Increase to 15 mg if needed after the initial period if the patient tolerates the lower dose well 1
- Further titration to 30-45 mg may be considered in patients with inadequate response, but proceed cautiously with extended intervals between dose changes 1
Key Monitoring Parameters
Watch closely for:
- Excessive sedation and drowsiness - The most common adverse effects, particularly problematic in elderly patients who are at increased fall risk 3, 4
- Orthostatic hypotension - Can contribute to falls and injury 3
- Weight gain and increased appetite - Occurs in approximately 10% of patients 3
- Cognitive changes or hallucinations - Rare but serious neuropsychiatric effects that elderly patients are more susceptible to 2
Important Clinical Considerations
Timing of administration: Give as a single evening dose at bedtime to minimize daytime sedation 1, 4
Drug interactions: Dose adjustments may be needed with:
- Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) - may require dose reduction 1
- Cimetidine - may require dose reduction 1
- Strong CYP3A4 inducers (e.g., carbamazepine, phenytoin) - may require dose increase 1
Renal/hepatic impairment: Further dose reduction and careful titration is recommended in elderly patients with compromised renal or hepatic function, as mirtazapine is extensively metabolized hepatically and excreted renally 3, 5
Discontinuation: Taper gradually rather than stopping abruptly to minimize withdrawal symptoms 1
Advantages in Elderly Population
Mirtazapine offers several benefits for appropriate elderly patients:
- Minimal anticholinergic effects compared to tricyclic antidepressants, reducing risk of confusion, urinary retention, and constipation 3, 5
- No sexual dysfunction unlike SSRIs 6, 4
- Beneficial effects on sleep and anxiety which are common comorbidities in elderly depression 7, 5
- Safe in overdose with minimal cardiovascular or respiratory effects 4