What is the recommended initial dosage and titration schedule for mirtazapine (Remeron)?

How to Start Mirtazapine

Start mirtazapine at 15 mg once daily at bedtime, and if there is inadequate response after 1-2 weeks, increase the dose up to a maximum of 45 mg per day, with dose changes made no more frequently than every 1-2 weeks. 1

Initial Dosing

• Begin with 15 mg once daily, administered orally in the evening prior to sleep 1
• This starting dose is supported by FDA labeling and represents the standard approach across all patient populations 1
• The bedtime dosing takes advantage of mirtazapine's sedating properties, which can help address sleep disturbances commonly associated with depression 2, 3

Titration Schedule

• If patients do not have adequate response to the initial 15 mg dose, increase up to a maximum of 45 mg per day 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 American College of Physicians recommends assessing therapeutic response and adverse effects within 1-2 weeks of treatment initiation 3

Timeline for Response

• Begin evaluating patient status within 1-2 weeks of starting treatment 3
• Some patients may experience improvement in sleep disturbances and anxiety symptoms within the first week 4
• Full antidepressant effect typically occurs within 2-4 weeks, though clinical onset may be seen as early as 1 week 4, 5
• If the patient does not have an adequate response within 6-8 weeks, treatment modification is strongly recommended 3

Pre-Treatment Screening

• Screen all patients for personal or family history of bipolar disorder, mania, or hypomania before initiating mirtazapine 1
• This is critical to avoid precipitating manic episodes in patients with undiagnosed bipolar disorder 1

Drug Interaction Considerations

When starting mirtazapine, adjust dosing based on concomitant medications:

• With strong CYP3A inducers (carbamazepine, phenytoin, rifampin): An increase in mirtazapine dosage may be needed 1
• With strong CYP3A4 inhibitors (ketoconazole, clarithromycin): A decrease in mirtazapine dosage may be needed 1
• With cimetidine: A decrease in mirtazapine dosage may be needed 1

MAOI Considerations

• At least 14 days must elapse between discontinuation of an MAOI antidepressant and initiation of mirtazapine 1
• At least 14 days must elapse after stopping mirtazapine before starting an MAOI antidepressant 1

Common Side Effects to Anticipate

Counsel patients about expected side effects at initiation:

• Somnolence/sedation (most common) 3, 4
• Increased appetite and weight gain 3, 4
• Dry mouth 3, 4
• Dizziness 4

Note that sedation is often dose-related and may paradoxically decrease at higher therapeutic doses (≥15 mg) 5

Ideal Patient Selection

Mirtazapine is particularly well-suited for patients with:

• Depression accompanied by insomnia or sleep disturbances 2, 3
• Depression with anorexia or weight loss 3
• Depression with prominent anxiety symptoms 2

The American Academy of Family Physicians notes that mirtazapine promotes sleep, appetite, and weight gain, making it especially appropriate for these presentations 2, 3

Monitoring Parameters

• Assess therapeutic response and adverse effects within 1-2 weeks 3
• Monitor for emergence of suicidal thoughts or behavior, particularly in younger patients 1
• Watch for signs of serotonin syndrome if combining with other serotonergic agents 1
• Continue treatment for 4-9 months after satisfactory response in first-episode depression 3
• For patients with 2 or more depressive episodes, even longer duration of therapy may be beneficial 3