Maximum Dosing of Mirtazapine
The maximum recommended dose of mirtazapine (Remeron) is 45 mg per day, administered as a single daily dose. 1
Dosing Guidelines
Mirtazapine follows a specific dosing protocol:
- Starting dose: 15 mg once daily, preferably in the evening prior to sleep 1
- Dose titration: Increase gradually based on response
- Maximum dose: 45 mg per day 1, 2
- Titration schedule: Dose changes should not be made in intervals of less than 1-2 weeks to allow sufficient time for evaluation of response 1
Dose-Response Relationship
Interestingly, the dose-response relationship of mirtazapine has some unique characteristics:
- Lower doses (7.5-15 mg) tend to be more sedating due to stronger antihistaminic effects 2
- Higher doses (30-45 mg) may have more noradrenergic and serotonergic effects 3
- The therapeutic plasma concentration range for mirtazapine is suggested to be 40-80 ng/mL 3
Special Populations
Dose adjustments may be necessary in certain populations:
- Hepatic impairment: Careful dosage titration and close monitoring for adverse events is recommended 4
- Renal impairment: Careful dosage titration and close monitoring for adverse events is recommended 4
- Elderly patients: Consider starting at a lower dose (7.5 mg) and titrating more slowly due to potential for increased side effects 2
Drug Interactions Affecting Dosing
Several drug interactions may necessitate dosage adjustments:
- Strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin): May require an increase in mirtazapine dosage 1
- Strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin): May require a decrease in mirtazapine dosage 1
- Cimetidine: May require a decrease in mirtazapine dosage 1
Clinical Considerations
- Mirtazapine has a half-life of 20-40 hours, making it suitable for once-daily dosing 5
- The drug shows linear pharmacokinetics over the dose range of 15-80 mg 6, though the maximum approved dose remains 45 mg
- When discontinuing treatment, gradually reduce the dosage rather than stopping abruptly to minimize withdrawal symptoms 1
Safety Profile at Maximum Dose
Mirtazapine appears to have a favorable safety profile even at maximum doses:
- Cases of overdose up to 975 mg have caused significant sedation but no cardiovascular or respiratory effects or seizures 5
- The most common side effects include drowsiness, dry mouth, increased appetite, and weight gain 4
- Unlike many other antidepressants, mirtazapine has minimal cardiovascular and anticholinergic effects 5
Remember that while 45 mg is the maximum FDA-approved dose, the optimal therapeutic dose should be determined based on individual response and tolerability, with careful monitoring for adverse effects.