What is the optimal dose of Remeron (mirtazapine)?

Optimal Dosing of Mirtazapine (Remeron)

The recommended starting dose of mirtazapine is 15 mg once daily, administered orally in the evening prior to sleep, with titration up to a maximum of 45 mg per day based on clinical response. 1

Initial Dosing and Titration

• The FDA-approved starting dose for mirtazapine is 15 mg once daily, taken preferably in the evening prior to sleep 1
• Dose changes should not be made in intervals of less than 1-2 weeks to allow sufficient time for evaluation of response 1
• If patients do not have an adequate response to the initial 15 mg dose, the dose can be increased up to a maximum of 45 mg per day 1
• In clinical trials, the mean effective dose ranged from 21 to 32 mg/day 1

Dose-Response Relationship

• Mirtazapine has a unique dose-response relationship for sedation - lower doses (7.5-15 mg) are more sedating than higher doses due to stronger H1 receptor antagonism at lower doses 2
• At higher doses (30-45 mg), the noradrenergic effects become more prominent, potentially reducing the sedative effects 3
• For patients with insomnia as a prominent symptom of depression, the 15 mg dose may be particularly effective 3

Special Populations

• In older adults, lower starting doses (approximately 7.5 mg) are often recommended due to greater risk of adverse drug reactions 4
• Patients with hepatic or renal impairment require careful dosage titration and close monitoring for adverse events 5
• Dose adjustments may be needed with concomitant medications that affect CYP3A4 enzyme activity 1

Clinical Efficacy

• Mirtazapine has demonstrated efficacy across the dose range of 15-45 mg/day for major depressive disorder 1
• It shows rapid onset of action, particularly for sleep disturbances and anxiety symptoms, which may improve within the first week of treatment 6
• Mirtazapine is as effective as tricyclic antidepressants and may have a more rapid onset of action than SSRIs 7

Side Effect Considerations

• Common side effects include drowsiness (23%), dry mouth (25%), increased appetite (11%), and weight gain (10%) 3
• Sedation is often most prominent at lower doses and may diminish at higher doses 8
• Mirtazapine has minimal cardiovascular and anticholinergic effects compared to tricyclic antidepressants 6
• Unlike SSRIs, mirtazapine has minimal sexual dysfunction side effects 8

Pharmacokinetic Considerations

• Mirtazapine has an elimination half-life of 20-40 hours, making it suitable for once-daily dosing 9
• The drug shows linear pharmacokinetics over the dose range of 15-80 mg 9
• Bioavailability is approximately 50% due to first-pass metabolism 9
• Steady-state plasma levels are achieved within 4-6 days of consistent dosing 9

Discontinuation

• When discontinuing mirtazapine, gradually reduce the dosage rather than stopping abruptly to minimize withdrawal symptoms 1
• Adverse reactions may occur upon discontinuation or dose reduction 1

Practical Recommendations

• For patients with prominent sleep disturbances, the 15 mg dose taken at bedtime is often sufficient 3
• For patients with inadequate antidepressant response at 15 mg, titration to 30 mg and then 45 mg may be necessary 1
• Administration on an empty stomach is advised to maximize effectiveness 3
• Monitor for excessive sedation, especially during the initial treatment period 2

Remember that the optimal dose of mirtazapine should be determined based on efficacy and tolerability for each individual patient, with careful attention to the unique dose-dependent side effect profile of this medication.