What is the recommended dosage and usage of Mirtazapine (generic name) for adults with major depressive disorder, considering factors such as age, medical history, and potential side effects?

Mirtazapine for Major Depressive Disorder in Adults

Recommended Starting Dosage

Start mirtazapine at 15 mg once daily, administered orally in the evening prior to sleep. 1

• If inadequate response occurs after 1-2 weeks of evaluation, increase the dose 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 response assessment 1
• For elderly, debilitated, or frail patients, consider starting at 7.5 mg at bedtime 2

Response Assessment and Treatment Duration

Begin assessing therapeutic response and adverse effects within 1-2 weeks of treatment initiation. 2

• If the patient does not show adequate response within 6-8 weeks, treatment modification is strongly recommended 2
• Continue treatment for 4-9 months after achieving satisfactory response in patients with a first episode of major depressive disorder 2
• For patients with 2 or more prior depressive episodes, extend treatment duration beyond 9 months 2

Clinical Advantages and Specific Indications

Mirtazapine is particularly suitable for patients with depression accompanied by insomnia, weight loss, or anxiety symptoms. 2

• Mirtazapine has a faster onset of action than fluoxetine, paroxetine, and sertraline, with significant improvements potentially visible within 1 week 2, 3
• The drug promotes sleep, appetite, and weight gain through its antihistaminic (H1) activity 2, 3
• It demonstrates important anxiolytic and sleep-improving effects related to its unique pharmacodynamic properties as a noradrenergic and specific serotonergic antidepressant (NaSSA) 3
• Mirtazapine is especially effective for sleep disturbances associated with depression and anxiety 2

Common Side Effects to Monitor

The most frequently reported adverse effects include:

• Somnolence/sedation (appears less frequent at higher dosages) 2, 3
• Increased appetite and weight gain 2, 3
• Dry mouth 2
• Sleep disorders 2
• Constipation or diarrhea 2

Importantly, mirtazapine does not cause sexual dysfunction, unlike SSRIs. 3

Special Populations and Dosage Adjustments

Hepatic or Renal Impairment

• Reduce dosage in patients with hepatic or renal impairment, as mirtazapine is extensively metabolized by the liver and excreted mainly in the urine 1, 4

Drug Interactions Requiring Dose Modification

Strong CYP3A Inducers (carbamazepine, phenytoin, rifampin):

• Increase mirtazapine dosage when these drugs are added 1
• Decrease mirtazapine dosage if the inducer is discontinued 1

Strong CYP3A4 Inhibitors (ketoconazole, clarithromycin):

• Decrease mirtazapine dosage when these drugs are added 1
• Increase mirtazapine dosage if the inhibitor is discontinued 1

Cimetidine:

• Decrease mirtazapine dosage with concomitant use 1
• Increase mirtazapine dosage if cimetidine is discontinued 1

Critical Safety Considerations

Screen all patients for personal or family history of bipolar disorder, mania, or hypomania before initiating mirtazapine. 1

• At least 14 days must elapse between discontinuing an MAOI antidepressant and starting mirtazapine 1
• At least 14 days must elapse after stopping mirtazapine before starting an MAOI antidepressant 1
• Gradually reduce the dosage rather than stopping abruptly to minimize discontinuation adverse reactions 1

When Mirtazapine May Not Be Appropriate

Do not use mirtazapine for mild depression or short treatment courses (less than 6-8 weeks). 2

• Antidepressants, including mirtazapine, are most effective in severe depression, not mild depression 2
• For mild depression, cognitive behavioral therapy is generally preferred over pharmacotherapy 2
• A 3-week treatment course is insufficient, as the acute treatment phase lasts 6-12 weeks 2

Alternative Options for Inadequate Response

If inadequate response to mirtazapine occurs after 6-8 weeks:

• Consider switching to an SSRI or SNRI 2
• Consider adding another antidepressant with a different mechanism of action 2
• For refractory insomnia with depression, alternatives include trazodone, olanzapine, zolpidem, chlorpromazine, quetiapine, or lorazepam 2