Maximum Dose of Mirtazapine
The maximum recommended dose of mirtazapine is 45 mg per day, administered as a single daily dose, preferably in the evening prior to sleep. 1
FDA-Approved Dosing Guidelines
- Start at 15 mg once daily in the evening, and if inadequate response occurs, increase up to a maximum of 45 mg per day 1
- Dose changes should not be made more frequently than every 1-2 weeks to allow sufficient time for evaluation of response 1
- The FDA label explicitly states that 45 mg daily is the upper limit for safe and effective use 1
Clinical Context and Real-World Practice
- While the FDA-approved maximum is 45 mg daily, some clinicians use doses above this regulatory-defined maximum to attain optimal efficacy in treatment-resistant cases 2
- However, for standard clinical practice, you should not exceed 45 mg daily as this is the evidence-based maximum with established safety data 1
- The effective dosage range in clinical trials was 15-45 mg daily, with most patients responding within this range 3, 4
Dosing Strategy for Optimization
- Begin with 15 mg daily for at least 1-2 weeks 1
- If response is inadequate after 6-8 weeks at 15 mg, increase to 30 mg daily 5
- If still insufficient after another 1-2 weeks at 30 mg, increase to the maximum of 45 mg daily 1
- Paradoxically, sedation may be more prominent at lower doses (15 mg) and can decrease at higher therapeutic doses 6
Important Dosing Modifications
- Reduce the dose when using strong CYP3A4 inhibitors (ketoconazole, clarithromycin) or cimetidine 1
- Increase the dose when using strong CYP3A inducers (carbamazepine, phenytoin, rifampin), as these can decrease mirtazapine levels by up to 60% 1, 7
- In hepatic or renal impairment, clearance decreases by 30% (moderate impairment) to 50% (severe renal impairment), requiring dose reduction 7
Safety Considerations at Maximum Dose
- The 45 mg maximum dose has been established based on clinical trials showing linear pharmacokinetics up to 80 mg/day, but efficacy and safety data support only up to 45 mg 6, 7
- Common side effects at therapeutic doses include somnolence, increased appetite, weight gain, and dry mouth 5, 3
- Overdoses up to 975 mg have caused significant sedation but no cardiovascular, respiratory effects, or seizures, indicating a relatively safe overdose profile 4