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

Mirtazapine (Remeron) Dosage 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
• Allow 1-2 weeks between dose adjustments to properly evaluate response 1
• If inadequate response to 15 mg, increase to 30 mg daily 1
• Further increase to 45 mg daily if needed, which is the maximum recommended dose 1
• Dose changes should not occur more frequently than every 1-2 weeks due to mirtazapine's long half-life of approximately 22 hours 2, 3

Duration of Treatment

• For first episodes of major depression, continue treatment for 4-9 months after satisfactory response 4
• For patients with 2 or more previous episodes, longer treatment duration is recommended 4
• Gradually taper the medication when discontinuing rather than stopping abruptly to minimize withdrawal symptoms 1

Clinical Efficacy and Onset of Action

• Mirtazapine has a relatively rapid onset of action compared to SSRIs, with improvements often seen within 1-2 weeks of treatment 3
• Response rates are similar to other antidepressants, with studies showing comparable efficacy to tricyclic antidepressants 2
• Remission rates of approximately 45% have been reported in clinical trials 5

Special Considerations for Specific Patient Populations

• For elderly or debilitated patients, a lower starting dose may be appropriate 4
• In patients with hepatic or renal insufficiency, careful dosage titration and close monitoring for adverse events is recommended 2
• Patients should be screened for bipolar disorder prior to starting mirtazapine 1

Therapeutic Benefits Beyond Depression

• Mirtazapine is particularly effective for patients with depression accompanied by:
  • Sleep disturbances (due to its sedative properties) 6
  • Poor appetite or weight loss (as it promotes appetite and weight gain) 6
  • Anxiety symptoms (due to its anxiolytic effects) 6

Common Side Effects and Management

• Most common side effects include:

  • Sedation/drowsiness (23% vs 14% with placebo) 2
  • Dry mouth (25% vs 16% with placebo) 2
  • Increased appetite (11% vs 2% with placebo) 2
  • Weight gain (10% vs 1% with placebo) 2

• Sedation tends to be more pronounced at lower doses (15 mg) due to higher affinity for H1 histamine receptors at lower concentrations 3

• Weight gain should be monitored, especially in patients concerned about weight 6

Drug Interactions and Dosage Modifications

• At least 14 days must elapse between discontinuation of an MAOI antidepressant and initiation of mirtazapine 1
• Dosage adjustments may be needed with:
  • Strong CYP3A inducers (increase mirtazapine dose may be needed) 1
  • Strong CYP3A inhibitors (decrease mirtazapine dose may be needed) 1
  • Cimetidine (decrease mirtazapine dose may be needed) 1

Common Pitfalls to Avoid

• Avoid rapid dose escalation (less than 1-2 weeks between increases) as this may increase side effect burden 1
• Do not abruptly discontinue mirtazapine; taper gradually to prevent withdrawal symptoms 1
• Monitor for rare but serious adverse effects such as agranulocytosis and neutropenia 2
• Be aware that sedation may be problematic for some patients requiring daytime alertness 6
• Mirtazapine may not be ideal for patients who need activation rather than sedation 6

Augmentation Strategies

• For patients with inadequate response to other antidepressants, mirtazapine can be used as an augmentation strategy 5
• When used as augmentation, start at 15 mg at bedtime with possible titration to 30 mg after one week 5
• Augmentation studies have shown response rates of 64% compared to 20% with placebo 5