Mirtazapine Dosage and Treatment Regimen for Major Depressive Disorder
The recommended dosage of mirtazapine for major depressive disorder is to start with 15 mg once daily at bedtime, with gradual titration up to 45 mg daily as needed, allowing 1-2 weeks between dose adjustments to evaluate response. 1
Initial Dosing and Titration
- Starting dose: 15 mg once daily, administered orally in the evening before sleep 1
- Titration schedule:
- Begin with 15 mg daily for 1-2 weeks
- If inadequate response, increase to 30 mg daily
- Further increases can be made up to a maximum of 45 mg daily 1
- Timing between dose adjustments: Allow 1-2 weeks between dose changes to properly evaluate response to a given dose 1
- Administration: Preferably taken in the evening due to its sedative properties 2
Efficacy and Onset of Action
- Mirtazapine is a potent and well-tolerated antidepressant that promotes sleep, appetite, and weight gain 2
- Clinical improvement typically begins within 2-4 weeks of starting treatment 3
- Sleep disturbances and anxiety symptoms may improve during the first week of treatment 3
- For optimal outcomes, treatment should continue for at least 6 months after significant improvement for a first episode of depression 4
Monitoring and Treatment Duration
- Regular assessment using standardized measures (e.g., PHQ-9) is essential
- Evaluate treatment efficacy at approximately 6 weeks and 12 weeks 4
- Response to treatment should be evaluated after 4 weeks; if no response, treatment is unlikely to be effective 4
- For patients with a first or second episode of major depression who respond well, continue full-dose treatment for at least 6 months after significant improvement 4
Special Considerations
Drug Interactions
- MAOIs: At least 14 days must elapse between discontinuation of an MAOI and initiation of mirtazapine, and vice versa 1
- CYP3A Inducers: May require increased mirtazapine dosage (e.g., with carbamazepine, phenytoin, rifampin) 1
- CYP3A Inhibitors: May require decreased mirtazapine dosage (e.g., with ketoconazole, clarithromycin) 1
- Cimetidine: May require decreased mirtazapine dosage 1
Discontinuation
- Adverse reactions may occur upon discontinuation or dose reduction
- Gradually reduce the dosage rather than stopping abruptly 1
Side Effect Profile
- Common side effects: Somnolence, increased appetite, weight gain, and dizziness 5
- Beneficial effects: Sedative effects can be helpful for patients with insomnia and depression 4
- Cardiovascular and anticholinergic effects: Minimal compared to tricyclic antidepressants 3
- Sexual dysfunction: Less common than with SSRIs 3
Pharmacological Mechanism
Mirtazapine has a unique mechanism of action:
- Blocks central α2-adrenergic auto- and heteroreceptors 6
- Antagonizes 5-HT2 and 5-HT3 receptors 6
- Enhances both noradrenergic and serotonergic neurotransmission 6
- Has high affinity for histamine H1 receptors (contributing to its sedative effects) 7
Clinical Pearls and Pitfalls
- Sedation: The sedative effect can be beneficial for patients with insomnia but may be problematic during daytime; administering at bedtime helps mitigate this issue 2
- Weight gain: Monitor for increased appetite and weight gain, which are more common with mirtazapine than placebo 6
- Bipolar screening: Screen patients for a personal or family history of bipolar disorder prior to initiating treatment 1
- Overdose safety: Mirtazapine appears to be relatively safe in overdose with minimal cardiovascular effects 3
- Elderly patients: Consider starting at lower doses (7.5 mg) in elderly patients due to increased sensitivity to side effects 2
Mirtazapine offers a valuable option for patients with major depressive disorder, particularly those with comorbid insomnia or appetite/weight loss issues, with a favorable side effect profile compared to many other antidepressants.