What is the recommended dosage and treatment protocol for Mirtazepine (Remeron) in patients with major depressive disorder?

Mirtazapine Dosing and Treatment Protocol for Major Depressive Disorder

Start mirtazapine at 15 mg once daily at bedtime, and if inadequate response occurs within 6-8 weeks, increase the dose up to a maximum of 45 mg daily, with dose changes made no more frequently than every 1-2 weeks. 1

Initial Dosing Strategy

• Begin with 15 mg once daily, administered orally in the evening prior to sleep 1
• The FDA-approved starting dose is 15 mg/day, which balances efficacy with tolerability 1
• Bedtime administration is preferred because mirtazapine promotes sleep and sedation, making it particularly suitable for patients with depression accompanied by insomnia 2

Dose Titration Protocol

• If patients do not achieve adequate response, 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 evaluation of response 1
• The effective dosage range is 15-45 mg daily 3, 4
• Some sources suggest an initial 4-day period at 15 mg, then increasing to 30 mg/day for 10 days, with further increases to 45 mg/day if needed 3

Timeline for Assessment and Response

• Begin assessing patient status, therapeutic response, and adverse effects within 1-2 weeks of treatment initiation 5, 2
• Mirtazapine demonstrates a faster onset of action than SSRIs (citalopram, fluoxetine, paroxetine, sertraline), with significant improvements potentially visible within the first 1-2 weeks 5, 6
• If the patient does not have an adequate response within 6-8 weeks, modify treatment 5, 2
• After 4 weeks, response rates between mirtazapine and other antidepressants become similar 5

Duration of Continuation Therapy

• Continue treatment for 4-9 months after a satisfactory response in patients with a first episode of major depressive disorder 5, 2
• For patients who have had 2 or more episodes of depression, an even longer duration of therapy may be beneficial 5, 2
• Continuation of antidepressant therapy reduces the risk for relapse 5

Pre-Treatment Screening

• Screen patients for personal or family history of bipolar disorder, mania, or hypomania prior to initiating mirtazapine 1
• At least 14 days must elapse between discontinuation of an MAOI antidepressant and initiation of mirtazapine, and vice versa 1

Dosage Modifications for Drug Interactions

• With strong CYP3A inducers (carbamazepine, phenytoin, rifampin): An increase in mirtazapine dosage may be needed; conversely, decrease the dose if the inducer is discontinued 1
• With strong CYP3A4 inhibitors (ketoconazole, clarithromycin): A decrease in mirtazapine dosage may be needed; conversely, increase the dose if the inhibitor is discontinued 1
• With cimetidine: A decrease in mirtazapine dosage may be needed; conversely, increase the dose if cimetidine is discontinued 1

Special Populations

• In patients with hepatic or renal insufficiency: Careful dosage titration and regular monitoring for adverse events is recommended 3
• Mirtazapine clearance may be reduced by hepatic or renal impairment since it is extensively metabolized by the liver and excreted mainly in the urine 7
• Second-generation antidepressants, including mirtazapine, show no differences in efficacy among elderly patients (65-80 years), very elderly patients (>80 years), or younger patients 5

Discontinuation Protocol

• Gradually reduce the dosage of mirtazapine rather than stopping abruptly whenever possible to avoid adverse reactions upon discontinuation 1

Common Adverse Effects to Monitor

• Drowsiness/sedation (23% vs 14% placebo), increased appetite (11% vs 2% placebo), and weight gain (10% vs 1% placebo) are the most common side effects 5, 2
• Dry mouth occurs in 25% vs 16% with placebo 5, 2
• Sedation is more common at subtherapeutic dosages and is reported less frequently when appropriate dosages (≥15 mg as a single evening dose) are used from the beginning 7
• Mirtazapine has minimal cardiovascular and anticholinergic effects, and essentially lacks serotonergic effects such as gastrointestinal symptoms and sexual dysfunction 4

Clinical Advantages

• Mirtazapine is particularly effective for patients with depression accompanied by insomnia, anxiety, anorexia, or weight loss 2, 8
• It has a faster onset of action than some SSRIs, with improvements in sleep disturbances and anxiety symptoms potentially occurring within the first week 5, 4
• Mirtazapine produces fewer anticholinergic, cardiac, and neurological adverse events compared to tricyclic antidepressants 3

Treatment-Resistant Depression

• If inadequate response to mirtazapine occurs after 6-8 weeks, consider switching to an SSRI or SNRI, or adding another antidepressant with a different mechanism of action 2
• Approximately 38% of patients do not achieve treatment response during 6-12 weeks with second-generation antidepressants, and 54% do not achieve remission 5