What is the recommended dosage and treatment approach for Mirtazepine (Remeron) in patients with major depressive disorder?

Mirtazapine Dosing and Treatment Approach 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

• Start with 15 mg once daily, preferably in the evening before sleep 1, 2
• If patients do not have an adequate response to the initial dose, increase gradually up to a maximum of 45 mg per day 1
• Dose adjustments should not be made more frequently than every 1-2 weeks to allow sufficient time for evaluation of response 1, 3
• Mirtazapine is potent and well-tolerated, particularly effective for patients with depression accompanied by insomnia or weight loss 2, 4

Monitoring and Response Timeline

• Begin assessing patient status, therapeutic response, and adverse effects within 1-2 weeks of treatment initiation 2, 4
• If the patient does not have an adequate response within 6-8 weeks, treatment modification is strongly recommended 4, 2
• Most patients show improvement within the first 1-2 weeks of treatment with continued improvements over time 3
• Treatment should continue for 4-9 months after a satisfactory response in patients with a first episode of major depressive disorder 4, 2
• For patients who have had 2 or more episodes of depression, an even longer duration of therapy is beneficial 4, 2

Side Effects and Management

• Common side effects include:

  • Sedation/drowsiness (most common) 3, 5
  • Increased appetite and weight gain 2, 3
  • Dry mouth 2, 5
  • Dizziness 3
  • Transient elevations in cholesterol levels and liver function tests 3

• Advantages of mirtazapine:

  • Faster onset of action than some SSRIs 2, 6
  • Promotes sleep, appetite, and weight gain (beneficial in patients with insomnia or weight loss) 4, 2
  • Lower incidence of sexual dysfunction compared to SSRIs 3, 5
  • Generally well-tolerated with fewer anticholinergic effects than tricyclic antidepressants 5

Special Considerations

• Screen patients for bipolar disorder prior to initiating treatment 1
• When switching from or to a monoamine oxidase inhibitor (MAOI), allow at least 14 days between discontinuation of one medication and initiation of the other 1
• Dose modifications may be needed with concomitant use of:
  • Strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin) - may need to increase mirtazapine dose 1
  • Strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin) - may need to decrease mirtazapine dose 1
  • Cimetidine - may need to decrease mirtazapine dose 1

Treatment Discontinuation

• Gradually reduce the dosage rather than stopping abruptly to minimize discontinuation symptoms 1
• Adverse reactions may occur upon discontinuation or dose reduction 1

Treatment-Resistant Depression

• For patients with inadequate response to standard antidepressants, mirtazapine may be effective as augmentation therapy 7
• A double-blind controlled trial showed a 64% response rate with mirtazapine augmentation compared to 20% with placebo 7
• Open-label studies suggest that approximately 38% of treatment-resistant patients may benefit from mirtazapine treatment 8

Mechanism of Action

• Mirtazapine has a unique mechanism of action as a noradrenergic and specific serotonergic antidepressant (NaSSA) 6, 5
• It enhances norepinephrine and serotonin neurotransmission by blocking central α2-adrenergic auto- and heteroreceptors 3, 5
• It also blocks 5-HT2 and 5-HT3 receptors, which contributes to its antidepressant effect and favorable side effect profile 3, 5