What is the recommended starting dose and titration schedule for mirtazapine (Remeron) in adults, including considerations for elderly patients, low body weight, hepatic impairment, and insomnia?

Mirtazapine (Remeron) Dosing

Standard Starting Dose and Titration

The FDA-approved starting dose of mirtazapine is 15 mg once daily, administered orally in the evening prior to sleep, with titration up to a maximum of 45 mg per day if needed. 1

• Dose changes should not be made in intervals of less than 1 to 2 weeks to allow sufficient time for evaluation of response 1
• The effective daily dosage range is 15-45 mg 2
• Full therapeutic effect typically requires 4-8 weeks of treatment, though sleep disturbances and anxiety symptoms may improve in the first week 3, 2

Elderly Patients

For elderly, debilitated, or frail patients, start at 7.5 mg at bedtime and titrate cautiously to a maximum of 30 mg at bedtime. 3, 4

• Increase by 7.5 mg increments every 5-7 days if needed, based on therapeutic response and tolerability 4
• Oral clearance of mirtazapine is reduced by 40% in elderly males and 10% in elderly females compared to younger patients 1
• Monitor for excessive sedation, falls risk, and orthostatic hypotension in elderly patients 4
• The elimination half-life is significantly longer in females (mean 37 hours) versus males (mean 26 hours) 1

Low Body Weight Patients

For patients with low body weight or who are debilitated, use the same reduced starting dose of 7.5 mg at bedtime as recommended for elderly patients. 3, 4

Hepatic Impairment

For patients with hepatic impairment, reduce the starting dose and titrate cautiously, as oral clearance is decreased by approximately 30% compared to patients with normal hepatic function. 1

• Close monitoring is required due to reduced drug clearance 5
• Consider starting at 7.5 mg and increasing more slowly than in patients with normal hepatic function 3

Renal Impairment

For patients with renal impairment, dose reduction is warranted, as total body clearance is reduced by approximately 30% with GFR 11-39 mL/min/1.73 m² and by 50% with GFR <10 mL/min/1.73 m². 1

Insomnia (Off-Label Use)

For insomnia, the American Academy of Sleep Medicine positions mirtazapine as a third-line option after benzodiazepine receptor agonists and ramelteon have been considered. 6

• The recommended starting dose for insomnia is 7.5 mg at bedtime, which can be titrated to 15-30 mg at bedtime if needed 3, 6
• In palliative care patients with refractory insomnia, 7.5-30 mg at bedtime is an acceptable option, particularly when the patient also has depression and loss of appetite 6
• Higher doses up to 45 mg may be used when treating comorbid depression 6
• A recent 2025 randomized controlled trial in older adults with chronic insomnia demonstrated that 7.5 mg daily significantly reduced insomnia severity compared to placebo, though 6 participants discontinued due to adverse events versus 1 in the placebo group 7

Important Drug Interactions Requiring Dose Adjustment

Strong CYP3A4 inducers (carbamazepine, phenytoin) increase mirtazapine clearance approximately 2-fold, requiring dose increases of mirtazapine. 1

Strong CYP3A4 inhibitors (ketoconazole, clarithromycin) and cimetidine require dose reductions of mirtazapine. 1

• Cimetidine increases mirtazapine AUC by more than 50% 1

Administration and Timing

Administer as a single dose at bedtime to take advantage of sedative properties. 3, 4, 1

• Food has minimal effect on absorption 1
• Peak plasma concentrations are reached within approximately 2 hours post-dose 1
• Steady state plasma levels are attained within 5 days 1

Discontinuation

Gradually reduce the dosage rather than stopping abruptly to minimize withdrawal symptoms. 3, 1

• Discontinuing over 10 to 14 days limits withdrawal symptoms 3

Critical Safety Considerations

Avoid combining mirtazapine with other sedating medications without careful assessment, as additive CNS depression increases fall risk, especially in older adults. 6

• Screen for bipolar disorder prior to initiating treatment 1
• At least 14 days must elapse between discontinuation of an MAOI and initiation of mirtazapine, and vice versa 1
• Monitor for weight gain, increased appetite, and sedation—the most common adverse effects 3, 5, 2