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

Mirtazapine Dosage and Treatment Regimen 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 titration up to a maximum of 45 mg per day based on clinical response. 1

Initial Dosing and Titration

• Begin with 15 mg once daily, preferably in the evening prior to sleep 1, 2
• If inadequate response occurs, increase the dose in intervals of not less than 1-2 weeks to allow sufficient time for evaluation of response 1
• Titrate up to a maximum of 45 mg per day as needed for clinical response 1, 2
• Mirtazapine is potent and well-tolerated, particularly effective for promoting sleep, appetite, and weight gain in depressed patients 3

Monitoring and Response Timeline

• Begin assessing therapeutic response and adverse effects within 1-2 weeks of treatment initiation 2
• A full therapeutic trial requires at least 4-8 weeks of treatment 3
• If the patient does not have an adequate response within 6-8 weeks, treatment modification is strongly recommended 2
• Mirtazapine has a faster onset of action than some SSRIs (citalopram, fluoxetine, paroxetine, or sertraline), with noticeable effects often beginning within 1-2 weeks 3, 2

Treatment Duration

• Continue treatment for 4-9 months after a satisfactory response in patients with a first episode of major depressive disorder 2
• For patients who have had 2 or more episodes of depression, a longer duration of therapy may be beneficial 2
• After 9 months of treatment, consider dosage reduction to reassess the need for continued medication 3
• When discontinuing, gradually reduce the dosage rather than stopping abruptly to minimize withdrawal symptoms 1

Special Considerations

Drug Interactions

• At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of mirtazapine 1
• Similarly, at least 14 days must elapse after stopping mirtazapine before starting an MAOI antidepressant 1
• Dosage adjustments may be needed with concomitant use of:
  • 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

Screening Before Treatment

• Prior to initiating treatment, screen patients for a personal or family history of bipolar disorder, mania, or hypomania to avoid triggering manic episodes 1

Common Side Effects

• Sedation/drowsiness (most common side effect) 4
• Increased appetite and weight gain 3, 4
• Dry mouth 2, 5
• Dizziness 4
• Transient elevations in cholesterol levels and liver function tests 4

Advantages for Specific Patient Populations

• Particularly beneficial for patients with depression accompanied by:
  • Insomnia or sleep disturbances 2, 5
  • Decreased appetite or weight loss 2
  • Anxiety symptoms 6

Clinical Pearls

• Mirtazapine has minimal cardiovascular and anticholinergic effects compared to tricyclic antidepressants 5
• Unlike SSRIs, mirtazapine has minimal sexual dysfunction side effects 5, 4
• The sedating effects are often more pronounced at lower doses (15 mg) than at higher doses (30-45 mg) due to the predominance of histamine H1 receptor blockade at lower doses 7
• Mirtazapine can be used as monotherapy or as augmentation therapy in treatment-resistant depression 8

Common Pitfalls to Avoid

• Initiating at too high a dose, which can lead to excessive sedation and poor tolerability 1
• Changing doses too quickly (less than 1-2 weeks between adjustments) 1, 3
• Discontinuing abruptly, which may lead to withdrawal symptoms 1
• Failing to monitor for rare but serious adverse effects such as agranulocytosis or neutropenia 7
• Not accounting for the potential weight gain, which can be significant in some patients 4