Mirtazapine Dosing for Major Depressive Disorder
Start mirtazapine at 15 mg once daily at bedtime, and if inadequate response occurs, increase up to a maximum of 45 mg daily, with dose changes made no more frequently than every 1-2 weeks. 1
Initial Dosing
- Begin with 15 mg once daily, administered orally in the evening prior to sleep 1
- This starting dose is supported by both FDA labeling and clinical guidelines 2, 1
- The bedtime administration takes advantage of mirtazapine's sedating properties, which can improve sleep disturbances often present in depression 2, 3
Dose Titration
- If patients do not respond adequately to 15 mg, increase the dose up to a maximum of 45 mg per day 1
- Wait at least 1-2 weeks between dose adjustments to allow sufficient time for evaluation of therapeutic response 1
- The effective dosage range is 15-45 mg daily 3, 4
- Some older literature mentions doses up to 80 mg/day, but the FDA-approved maximum is 45 mg daily 1, 5
Timeline for Response Assessment
- Begin assessing therapeutic response and adverse effects within 1-2 weeks of treatment initiation 2
- Mirtazapine has a faster onset of action than some SSRIs (fluoxetine, paroxetine, sertraline), with sleep and anxiety symptoms potentially improving within the first week 2, 3
- If inadequate response occurs within 6-8 weeks, treatment modification is strongly recommended 2
- Full antidepressant effect typically occurs within 2-4 weeks 3
Duration of Treatment
- Continue treatment for 4-9 months after satisfactory response in patients with first-episode major depressive disorder 2
- For patients with 2 or more depressive episodes, consider even longer duration of therapy 2
Dosage Modifications for Drug Interactions
Strong CYP3A Inducers
- Increase mirtazapine dose when used concomitantly with strong CYP3A inducers (carbamazepine, phenytoin, rifampin) 1
- Conversely, decrease dose if the inducer is discontinued 1
Strong CYP3A Inhibitors
- Decrease mirtazapine dose when used with strong CYP3A4 inhibitors (ketoconazole, clarithromycin) 1
- Increase dose if the inhibitor is discontinued 1
Cimetidine
- Decrease mirtazapine dose when used concomitantly with cimetidine 1
- Increase dose if cimetidine is discontinued 1
Discontinuation
- Gradually taper the dose rather than stopping abruptly to minimize withdrawal symptoms 1
- Adverse reactions may occur upon abrupt discontinuation or rapid dose reduction 1
Special Populations
- In patients with hepatic or renal impairment, use careful dose titration with regular monitoring 6
- Mirtazapine is extensively metabolized by the liver and excreted mainly in urine, so clearance may be reduced in these populations 5
Important Clinical Considerations
- Screen all patients for personal or family history of bipolar disorder, mania, or hypomania before initiating treatment 1
- Allow at least 14 days between discontinuing an MAOI and starting mirtazapine, and vice versa 1
- The elimination half-life of 20-40 hours supports once-daily dosing 3, 5
Common Side Effects to Monitor
- Somnolence/sedation (often dose-related and may decrease at higher therapeutic doses) 2, 4
- Increased appetite and weight gain 2, 4
- Dry mouth 2, 4
- Constipation or diarrhea 2
Clinical Advantages
- Particularly suitable for patients with depression accompanied by insomnia or weight loss due to its sleep-promoting and appetite-stimulating properties 2
- Minimal cardiovascular and anticholinergic effects compared to tricyclic antidepressants 3
- Lacks serotonergic side effects such as gastrointestinal symptoms and sexual dysfunction common with SSRIs 3, 5