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

Mirtazapine Dosage and Treatment Regimen for Major Depressive Disorder

The recommended dosing regimen for mirtazapine in major depressive disorder is to start at 15 mg once daily at bedtime, with titration up to 30-45 mg daily as needed for optimal antidepressant effect. 1, 2

Initial Dosing and Titration

• Starting dose: 15 mg once daily, administered orally in the evening prior to sleep 1

  • For elderly patients or those with hepatic/renal impairment: Consider a lower starting dose of 7.5 mg 2

• Dose titration:

  • If inadequate response to initial 15 mg dose, increase dose up to a maximum of 45 mg per day 1
  • Allow 1-2 weeks between dose adjustments to properly evaluate response 1
  • Optimal antidepressant dose is typically 30-45 mg daily 2

Pharmacological Considerations

• Lower doses (7.5-15 mg) tend to be more sedating due to predominant H1 receptor antagonism 2
• Higher doses (30-45 mg) provide optimal antidepressant effect 2
• Once-daily dosing is supported by mirtazapine's 20-40 hour half-life 2, 3
• Evening dosing minimizes daytime impairment from sedation 2

Duration of Treatment

• Assess therapeutic response after 4-8 weeks of treatment 2
• Continue treatment for 4-9 months after satisfactory response for first episode of depression 2
• Longer duration may be beneficial for recurrent depression 2
• When discontinuing, gradually reduce the dosage rather than stopping abruptly to minimize withdrawal symptoms 1

Dose Adjustments for Special Situations

• Drug interactions:

  • 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
  • MAOIs: Allow at least 14 days between discontinuation of an MAOI and initiation of mirtazapine, and vice versa 1

• Special populations:

  • Elderly patients: Lower starting doses (7.5-15 mg) due to reduced clearance 2
  • Hepatic or renal impairment: Dose adjustments may be required 2

Common Side Effects and Monitoring

• Most common adverse effects:

  • Somnolence (54%)
  • Dry mouth (25%)
  • Increased appetite (17%)
  • Weight gain (10%) 2

• Regular monitoring recommended for:

  • Therapeutic response using standardized depression scales
  • Side effects, particularly sedation and weight gain
  • Blood pressure, weight, and metabolic parameters 2

Clinical Pearls

• Mirtazapine may improve sleep disturbances and anxiety symptoms within the first week of treatment, while full antidepressant effect typically takes 2-4 weeks 3
• Unlike many other antidepressants, mirtazapine has minimal anticholinergic effects and lacks serotonergic side effects such as gastrointestinal symptoms and sexual dysfunction 3
• Screen for bipolar disorder prior to initiating treatment 1