Mirtazapine Dosing in Adults
Start mirtazapine at 15 mg once daily at bedtime, and if needed after 1-2 weeks, increase up to a maximum of 45 mg daily. 1
Standard Dosing Protocol
- Initial dose: 15 mg once daily, preferably in the evening prior to sleep 1
- Dose titration: Increase as needed up to 45 mg daily maximum 1
- Timing of dose changes: Wait at least 1-2 weeks between dose adjustments to allow adequate time to evaluate response 1
- The effective dosage range is 15-45 mg daily, with once-daily bedtime administration enabled by the 20-40 hour elimination half-life 2, 3
Clinical Response Timeline
- Begin assessing therapeutic response and adverse effects within 1-2 weeks of starting treatment 4
- Sleep disturbances and anxiety symptoms may improve within the first week, while full antidepressant effects typically emerge in 2-4 weeks 2, 5
- If inadequate response after 6-8 weeks, treatment modification is strongly recommended 4
Duration of Treatment
- Continue treatment for 4-9 months after satisfactory response in first-episode major depressive disorder 4
- For patients with 2 or more depressive episodes, longer duration therapy is beneficial 4
Dosage Adjustments for Drug Interactions
- With strong CYP3A inducers (carbamazepine, phenytoin, rifampin): Increase mirtazapine dose; decrease when inducer discontinued 1
- With strong CYP3A inhibitors (ketoconazole, clarithromycin): Decrease mirtazapine dose; increase when inhibitor discontinued 1
- With cimetidine: Decrease mirtazapine dose; increase when cimetidine discontinued 1
Special Clinical Considerations
- Mirtazapine is particularly suitable for patients with depression accompanied by insomnia or weight loss due to its sedating properties and appetite-stimulating effects 4, 6
- The sedative effects help address sleep disturbances that commonly accompany depression 7
- Evening administration is recommended to leverage sedative properties for sleep benefit 7
Common Adverse Effects to Monitor
- Most common: Somnolence/sedation, increased appetite, weight gain, dry mouth 4, 1, 2
- Sedation is more prominent at lower doses and may decrease as dose increases to therapeutic range 5
- Mirtazapine has minimal anticholinergic, cardiovascular, and sexual dysfunction side effects compared to tricyclic antidepressants and SSRIs 2, 5
Discontinuation
- Gradually taper the dose rather than stopping abruptly to minimize withdrawal symptoms 1
Important Precautions
- Screen 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
- Exercise caution in patients with obstructive sleep apnea, as mirtazapine may worsen this condition 7