What is the recommended dosing of mirtazapine for older adults, considering potential risks such as dizziness, hypotension, and sedation, as well as impaired renal function?

Mirtazapine Dosing for Older Adults

Start mirtazapine at 7.5 mg at bedtime in older adults, then titrate to 15-30 mg at bedtime based on response and tolerability. 1

Starting Dose

• Begin with 7.5 mg at bedtime in older patients to minimize sedation, dizziness, and orthostatic hypotension 1
• This lower starting dose (approximately 50% of the standard adult starting dose) is recommended for all older adults due to their significantly greater risk of adverse drug reactions 1

Titration Strategy

• Increase to 15 mg at bedtime after 4-7 days if the initial dose is well tolerated 1
• Target therapeutic dose is 15-30 mg at bedtime for most older adults 1
• Use small dose increments (7.5 mg increases) at intervals of at least 5-7 days to allow adequate monitoring for adverse effects 1
• Maximum dose of 30 mg at bedtime is typically sufficient for older adults, though doses up to 45 mg may be considered in select cases 1

Special Considerations for Renal Impairment

• Reduce doses and titrate more cautiously in patients with moderate to severe renal impairment 1
• Monitor closely for accumulation of drug and increased adverse effects, as mirtazapine is primarily renally excreted 2, 3

Key Adverse Effects to Monitor

The most problematic adverse effects in older adults include:

• Sedation and drowsiness (occurs in 19-23% of patients) - this is dose-dependent and paradoxically may be worse at lower doses (below 15 mg) 2, 4
• Orthostatic hypotension and dizziness - monitor blood pressure in sitting and standing positions, especially during dose titration 1
• Increased appetite and weight gain (occurs in 10-11% of patients) - may be beneficial in frail older adults with poor appetite 2, 4
• Falls risk - the combination of sedation, dizziness, and potential orthostatic hypotension increases fall risk in older adults 1

Clinical Advantages in Older Adults

Mirtazapine offers several benefits that make it particularly useful in certain older patients:

• Promotes sleep - beneficial for depressed older adults with insomnia when dosed at bedtime 1, 4
• Stimulates appetite - useful in older adults with depression-related anorexia and weight loss 1, 4
• Minimal anticholinergic effects - safer than tricyclic antidepressants in older adults 1, 2
• No sexual dysfunction - unlike SSRIs, mirtazapine does not cause sexual side effects 4, 5
• No significant cardiovascular effects - safer than tricyclics in patients with cardiac disease 4

Critical Safety Warnings

• Monitor for agranulocytosis - though rare (approximately 1 in 1,000), this is the most serious adverse effect and typically occurs in the first few weeks of treatment 5
• Avoid in patients taking multiple sedating medications - the additive sedation increases fall risk significantly 1
• Safe in overdose - causes primarily sedation without significant cardiovascular or respiratory depression 4, 5

Comparison to Other Antidepressants in Older Adults

While SSRIs like citalopram and escitalopram are often considered first-line 1, mirtazapine is preferred when:

• The patient has significant insomnia requiring treatment 1, 4
• Weight loss and poor appetite are prominent features 1, 4
• The patient has experienced sexual dysfunction with SSRIs 5
• Anxiety symptoms are prominent and require rapid control 4, 6

Avoid fluoxetine and paroxetine in older adults - fluoxetine has greater risk of agitation, and paroxetine has more anticholinergic effects 1