What is the dosage and treatment protocol for Remeron (mirtazapine) in patients with major depressive disorder?

Mirtazapine (Remeron) Dosage and Treatment Protocol for Major Depressive Disorder

The recommended starting dose of mirtazapine for major depressive disorder is 15 mg once daily, administered orally in the evening prior to sleep, with gradual titration up to a maximum of 45 mg per day based on clinical response. 1

Initial Dosing and Titration

• The FDA-approved starting dose is 15 mg once daily, preferably administered in the evening before bedtime 1
• Dose increases should not be made in intervals of less than 1-2 weeks to allow sufficient time for evaluation of response 1, 2
• If patients do not have an adequate response to the initial 15 mg dose, the dose can be increased up to a maximum of 45 mg per day 1
• For elderly or sensitive patients, a lower starting dose of 7.5 mg may be appropriate to minimize sedative effects 3

Treatment Duration and Phases

• Treatment for major depression occurs in three phases 4:
  • Acute phase (6-12 weeks)
  • Continuation phase (4-9 months)
  • Maintenance phase (≥1 year)
• Treatment for a first episode of major depression should last at least 4 months after a satisfactory response 4, 2
• For patients who have had 2 or more episodes of depression, a longer duration of therapy may be beneficial 2

Monitoring and Response Timeline

• Begin assessing patient status, therapeutic response, and adverse effects within 1-2 weeks of treatment initiation 2
• If the patient does not have an adequate response within 6-8 weeks, treatment modification is strongly recommended 2
• Clinical improvement may be observed as early as the first 1-2 weeks of treatment, particularly for sleep disturbances and anxiety symptoms 5, 2
• Full therapeutic effect is typically observed at 4-6 weeks of treatment 6

Common Side Effects and Management

• Most common side effects include 4, 6:

  • Drowsiness/sedation (most common)
  • Increased appetite and weight gain
  • Dry mouth
  • Dizziness
  • Constipation or diarrhea

• Important notes on side effects:

  • Sedation tends to be more pronounced at lower doses (15 mg) and may actually decrease at higher doses (30-45 mg) 6, 7
  • Mirtazapine has minimal cardiovascular and anticholinergic effects 5
  • Unlike SSRIs, mirtazapine has minimal sexual side effects 8

Special Considerations

• Screen for bipolar disorder prior to initiating treatment 1
• Allow at least 14 days between discontinuing an MAOI antidepressant and starting mirtazapine, and vice versa 1
• Dose adjustments may be needed with concomitant use of strong CYP3A inducers or inhibitors 1
• When discontinuing mirtazapine, gradually reduce the dosage rather than stopping abruptly to minimize withdrawal symptoms 1

Clinical Advantages

• Mirtazapine has a faster onset of action than some SSRIs 2
• It is particularly effective for patients with depression accompanied by insomnia or weight loss 2, 6
• It enhances both noradrenergic and specific serotonergic neurotransmission through its unique mechanism of action 8

Common Pitfalls and Caveats

• Avoid rapid dose escalation; allow 1-2 weeks between dose adjustments to properly assess response and tolerability 1, 2
• Be cautious with elderly patients who may be more sensitive to sedative effects; consider starting at 7.5 mg 3
• Monitor for excessive weight gain, which may affect long-term adherence 6
• In rare cases, mirtazapine has been associated with potentially serious hematological changes (e.g., agranulocytosis and neutropenia) 7
• If inadequate response occurs, consider switching to an SSRI or SNRI, or adding another antidepressant with a different mechanism of action 2