Mirtazapine Dosing Regimen
The recommended dosing regimen for mirtazapine is to start with 15 mg once daily administered orally in the evening prior to sleep, with dose increases up to a maximum of 45 mg per day if needed, allowing 1-2 weeks between dose adjustments to evaluate response. 1
Initial Dosing and Titration
- Start with 15 mg once daily, preferably in the evening prior to sleep 1
- If inadequate response occurs, increase the dose after 1-2 weeks 1
- Titrate up to a maximum of 45 mg per day as needed 1, 2
- The elimination half-life of 20-40 hours supports once-daily dosing 3, 4
Pharmacological Considerations
- Mirtazapine has a unique mechanism of action as a noradrenergic and specific serotonergic antidepressant (NaSSA) 5
- It blocks presynaptic alpha-2 adrenergic receptors and postsynaptic serotonin 5-HT2 and 5-HT3 receptors 3
- Bioavailability is approximately 50%, with peak plasma concentrations reached within 2-3 hours 5, 4
- Steady state is typically reached within 4-6 days of consistent dosing 4
Dose Modifications
- Patients with hepatic or renal impairment may require lower doses due to decreased clearance 4
- Strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin) may necessitate higher mirtazapine doses 1
- Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) may require lower mirtazapine doses 1
- Cimetidine co-administration may require dose reduction of mirtazapine 1
Clinical Pearls
- Therapeutic effects on depression typically begin in 2-4 weeks, though sleep and anxiety symptoms may improve within the first week 3
- Lower doses (7.5-15 mg) may be more sedating than higher doses due to the predominance of histamine H1 receptor blockade at lower doses 6, 7
- Higher doses (30-45 mg) may have more noradrenergic effects and potentially less sedation 7
- Common side effects include somnolence/sedation (23%), dry mouth (25%), increased appetite (11%), and weight gain (10%) 8, 7
Discontinuation
- Gradually taper the dose rather than stopping abruptly to minimize discontinuation symptoms 1
- Monitor for withdrawal symptoms during dose reduction 1
Special Considerations
- Screen for bipolar disorder prior to initiating treatment 1
- Allow at least 14 days between discontinuing MAOIs and starting mirtazapine, and vice versa 1
- Mirtazapine appears to have a very low potential for inducing seizures, making it potentially safer in patients with seizure disorders 5, 7
By following this dosing regimen and considering these clinical factors, mirtazapine can be effectively used to treat depression while minimizing adverse effects and optimizing therapeutic outcomes.