What is the recommended starting dose and titration rate for mirtazapine (Remeron) in the treatment of Major Depressive Disorder (MDD)?

Mirtazapine Starting Dose and Titration for Major Depressive Disorder

Start mirtazapine at 15 mg once daily at bedtime, and titrate in increments of 15 mg every 1-2 weeks as needed, up to a maximum of 45 mg daily. 1

Starting Dose

• The FDA-approved starting dose is 15 mg once daily, administered orally, preferably in the evening prior to sleep 1
• In older adults, consider starting at approximately 50% of the standard adult dose (7.5 mg) due to greater risk of adverse drug reactions 2
• The 15 mg starting dose is supported by multiple research studies demonstrating efficacy and tolerability at this initial dosage 3, 4

Titration Rate and Schedule

• Dose changes should not be made in intervals of less than 1-2 weeks to allow sufficient time for evaluation of response to a given dose 1
• If patients do not have an adequate response to the initial 15 mg dose, increase the dose up to a maximum of 45 mg per day 1
• The effective daily dosage range is 15-45 mg, with titration typically occurring in 15 mg increments 3
• One research protocol suggested starting at 15 mg/day for 4 days, then increasing to 30 mg/day for 10 days, with further increases to 45 mg/day if needed 5

Timeline for Response Assessment

• Begin assessing patient status, therapeutic response, and adverse effects within 1-2 weeks of treatment initiation 6
• Mirtazapine may show faster onset of action compared to some SSRIs, with sleep disturbances and anxiety symptoms potentially improving in the first week of treatment 3
• Clinical improvement is typically noted within 2-4 weeks, though some patients may show significant improvement as early as 1-2 weeks 3, 7
• If the patient does not have an adequate response within 6-8 weeks, treatment modification is strongly recommended 6

Important Clinical Considerations

• Screen for bipolar disorder prior to initiating mirtazapine by assessing personal or family history of bipolar disorder, mania, or hypomania 1
• Mirtazapine is particularly suitable for patients with depression accompanied by insomnia or weight loss, as it promotes sleep, appetite, and weight gain 6
• Common side effects to monitor include somnolence/sedation (which may be more prominent at lower doses), increased appetite, weight gain, and dry mouth 6, 3

Dose Adjustments for Drug Interactions

• Decrease mirtazapine dose with concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) or cimetidine 1
• Increase mirtazapine dose with concomitant use of strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin) 1

Discontinuation

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

Maintenance Therapy

• Continue treatment for 4-9 months after a satisfactory response in patients with a first episode of major depressive disorder 6
• For patients who have had 2 or more episodes of depression, an even longer duration of therapy may be beneficial 6