What is the recommended dosing for mirtazapine (Remeron) in the treatment of adult depression?

Mirtazapine Dosing for Adult Depression

The recommended starting dose of mirtazapine for adult depression is 15 mg once daily at bedtime, with titration up to a maximum of 45 mg per day based on response, and dose changes should not occur more frequently than every 1-2 weeks. 1

Initial Dosing

• Start with 15 mg once daily, preferably in the evening prior to sleep 1
• This starting dose is supported by FDA labeling and represents the standard approach for most adult patients 1
• The evening administration timing capitalizes on mirtazapine's sedating properties, which can help address sleep disturbances commonly associated with depression 2

Dose Titration

• If inadequate response to 15 mg, increase the dose up to a maximum of 45 mg per day 1
• Wait at least 1-2 weeks between dose adjustments to allow sufficient time to evaluate response 1
• The effective dosage range is 15-45 mg daily 2, 3
• Mean effective doses in clinical trials ranged from 21-32 mg/day 1

Special Population Considerations

Older Adults

• Start at approximately 50% of the standard adult dose (7.5 mg) due to significantly greater risk of adverse drug reactions in older populations 2, 4
• Mirtazapine is considered a preferred agent in older adults due to its favorable adverse effect profile compared to tricyclic antidepressants 2

Patients with Hepatic or Renal Impairment

• Consider dose reduction in patients with hepatic or renal disease 2
• Mirtazapine is extensively metabolized hepatically and excreted renally, so clearance may be reduced in these populations 5

Drug Interaction Dosing Adjustments

Strong CYP3A4 Inducers (e.g., carbamazepine, phenytoin, rifampin)

• Increase mirtazapine dose when used concomitantly 1
• Conversely, decrease dose if the inducer is discontinued 1

Strong CYP3A4 Inhibitors (e.g., ketoconazole, clarithromycin)

• Decrease mirtazapine dose when used concomitantly 1
• Increase dose if the inhibitor is discontinued 1

Cimetidine

• Decrease mirtazapine dose with concomitant use 1
• Increase dose if cimetidine is discontinued 1

Clinical Considerations

Onset of Action

• Expect clinical improvement in 2-4 weeks, though sleep disturbances and anxiety may improve within the first week 3
• Some studies showed significant improvement as early as 1 week after starting treatment 5
• Full therapeutic effect typically observed at 4-6 weeks 6

Specific Clinical Advantages

• Particularly effective for patients with depression accompanied by sleep disturbances (promotes sleep) and poor appetite (promotes appetite and weight gain) 4
• May have more rapid onset of action than SSRIs 7
• Beneficial effects on anxiety symptoms associated with depression 5

Common Pitfalls to Avoid

• Do not adjust doses more frequently than every 1-2 weeks - insufficient time to assess response leads to inappropriate dose escalation 1
• Do not abruptly discontinue - gradually taper to minimize withdrawal symptoms 1
• Screen for bipolar disorder before initiating - antidepressants can precipitate manic episodes in undiagnosed bipolar disorder 1
• Allow at least 14 days between discontinuing an MAOI and starting mirtazapine, and vice versa 1
• Counsel patients about sedation, increased appetite, and weight gain - these are the most common adverse effects 3, 7

Duration of Treatment

• Continue treatment for 4-12 months after first episode of major depression 2
• Consider prolonged treatment for recurrent depression - patients with recurrent depression showed significantly lower relapse rates with continued mirtazapine treatment over 40 weeks 2, 1