Mirtazapine for Major Depressive Disorder
Recommended Dosage
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
Dosing Algorithm
- Initial dose: 15 mg once daily, preferably in the evening prior to sleep 1
- Dose titration: If inadequate response at 15 mg, increase dose up to maximum of 45 mg/day 1
- Timing of dose changes: Wait at least 1-2 weeks between dose adjustments to allow sufficient time for evaluation of therapeutic response 1
- Administration: Once-daily dosing at bedtime is enabled by the 20-40 hour elimination half-life 2
Monitoring and Treatment Duration
Begin assessing therapeutic response and adverse effects within 1-2 weeks of starting treatment, and if inadequate response occurs by 6-8 weeks, strongly consider treatment modification. 3
Response Timeline
- Early improvement: Sleep disturbances and anxiety symptoms may improve within the first 1-2 weeks 2
- Full antidepressant effect: Clinical response typically occurs within 2-4 weeks 2
- Speed advantage: Mirtazapine demonstrates statistically significantly faster onset of action compared to citalopram, fluoxetine, paroxetine, or sertraline, though response rates equalize after 4 weeks 4
Treatment Duration
- First episode of MDD: Continue treatment for 4-9 months after achieving satisfactory response 3
- Recurrent depression: Patients with 2 or more prior episodes benefit from even longer duration of therapy 3
Clinical Advantages and Specific Indications
Mirtazapine is particularly suitable for patients with depression accompanied by insomnia, weight loss, or anorexia due to its sedating properties and appetite-stimulating effects. 3
Specific Patient Populations
- Depression with insomnia: Mirtazapine is especially effective for sleep disturbances associated with depression 3
- Depression with weight loss/anorexia: The medication promotes appetite and weight gain, making it ideal for patients with these symptoms 3
- Elderly patients: Mirtazapine leads to rapid and sustained improvements in depressive symptoms in elderly populations 5
Important Adverse Effects to Monitor
Common Side Effects
- Sedation/somnolence: Most common adverse effect, particularly at lower doses 3, 2
- Increased appetite and weight gain: Occurs more commonly than with placebo 3, 2
- Dry mouth: Frequently reported 3
- Constipation or diarrhea: May occur 3
Tolerability Profile
- Minimal cardiovascular and anticholinergic effects 2
- Lacks serotonergic adverse effects: Essentially no gastrointestinal symptoms, insomnia, or sexual dysfunction typical of SSRIs 2
- Superior tolerability: Demonstrates better tolerability than tricyclic antidepressants and trazodone 6
Drug Interactions and Dose Adjustments
CYP3A4 Interactions
- Strong CYP3A4 inducers (carbamazepine, phenytoin, rifampin): Increase mirtazapine dose as needed; decrease dose if inducer is discontinued 1
- Strong CYP3A4 inhibitors (ketoconazole, clarithromycin): Decrease mirtazapine dose; increase dose if inhibitor is discontinued 1
Other Interactions
- Cimetidine: Decrease mirtazapine dose with concomitant use; increase dose if cimetidine is discontinued 1
Critical Safety Considerations
MAOI Interactions
Allow at least 14 days between discontinuing an MAOI and starting mirtazapine, and at least 14 days after stopping mirtazapine before starting an MAOI. 1
Bipolar Screening
Screen all patients for personal or family history of bipolar disorder, mania, or hypomania prior to initiating mirtazapine. 1
Discontinuation
Gradually taper mirtazapine rather than stopping abruptly to minimize discontinuation adverse reactions. 1
Treatment-Resistant Depression
If inadequate response to mirtazapine occurs after 6-8 weeks at adequate doses, consider switching to an SSRI or SNRI, or adding another antidepressant with a different mechanism of action 3. The STAR*D trial demonstrated that approximately 38% of patients do not achieve treatment response and 54% do not achieve remission with initial second-generation antidepressant therapy, with 1 in 4 patients becoming symptom-free after switching medications 4.