Mirtazapine Dosing for Depression

Start mirtazapine at 15 mg once daily at bedtime, and if inadequate response occurs after 1-2 weeks, increase up to a maximum of 45 mg daily. 1

Initial Dosing

Begin with 15 mg once daily, administered in the evening prior to sleep 1
The FDA-approved starting dose is specifically 15 mg/day, not lower 1
Once-daily bedtime dosing is enabled by the 20-40 hour elimination half-life 2, 3

Do not increase the dose more frequently than every 1-2 weeks to allow sufficient time to evaluate response to the current dose 1
If patients do not respond adequately to 15 mg, increase up to a maximum of 45 mg per day 1
The effective dosage range is 15-45 mg daily 4, 2
Mean effective doses in clinical trials ranged from 21-32 mg/day 1

Begin assessing therapeutic response and adverse effects within 1-2 weeks of starting treatment 5
If inadequate response occurs within 6-8 weeks, treatment modification is strongly recommended 5
Mirtazapine may have a faster onset of action than some SSRIs (fluoxetine, paroxetine, sertraline), with improvements in sleep and anxiety symptoms potentially occurring within the first week 4, 5, 2
Full antidepressant effect typically occurs in 2-4 weeks, similar to other antidepressants 2

Continue treatment for 4-12 months after achieving remission for a first episode of major depression 4, 5
For patients with recurrent depression (2 or more episodes), longer duration therapy is beneficial 5
Patients on continued mirtazapine experienced significantly lower relapse rates over 40 weeks compared to placebo 1

Mirtazapine is a preferred agent for older patients with depression 4
Use a "start low, go slow" approach, beginning at approximately 50% of the standard adult starting dose 4
It is particularly suitable for elderly patients with depression accompanied by insomnia or weight loss 5

Consider dose reduction in patients with hepatic or renal disease 4
Careful dosage titration and close monitoring for adverse effects is recommended 6

With strong CYP3A4 inducers (carbamazepine, phenytoin, rifampin): Increase mirtazapine dose; decrease when inducer is discontinued 1
With strong CYP3A4 inhibitors (ketoconazole, clarithromycin): Decrease mirtazapine dose; increase when inhibitor is discontinued 1
With cimetidine: Decrease mirtazapine dose; increase when cimetidine is discontinued 1

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

Mirtazapine is particularly effective for patients with depression accompanied by insomnia, anxiety, anorexia, or weight loss 5, 2
It promotes sleep, appetite, and weight gain, which can be therapeutic in appropriate patients 5
The drug has minimal cardiovascular, anticholinergic, gastrointestinal, and sexual dysfunction side effects compared to TCAs and SSRIs 2, 3

Somnolence/sedation, increased appetite, weight gain, dry mouth, and dizziness are the most common adverse effects 1, 2, 7
Sedation is often dose-related and may be more prominent at lower doses 3