Does increasing mirtazapine (Remeron) from 7.5mg to 15mg reduce or lose its nighttime sedative effect?

Does Increasing Mirtazapine from 7.5mg to 15mg Reduce Nighttime Sedation?

No, you do not lose the sedative effect when increasing mirtazapine from 7.5mg to 15mg—in fact, sedation may actually decrease at higher doses due to mirtazapine's unique pharmacology where antihistaminic effects (causing sedation) are more prominent at lower doses. 1, 2

Understanding Mirtazapine's Paradoxical Dose-Sedation Relationship

The common clinical concern about losing sedation with dose increases is based on a misunderstanding of mirtazapine's pharmacology:

• At lower doses (7.5mg), mirtazapine's sedative effects are primarily mediated through potent histamine H1 receptor antagonism, which causes significant drowsiness 1, 3

• At therapeutic doses (15mg and above), the noradrenergic effects become more prominent, which can actually reduce the sedation experienced at subtherapeutic doses 1, 2

• Multiple studies demonstrate that sedation is paradoxically more common at subtherapeutic dosages and is reported in substantially fewer patients when appropriate dosages (≥15mg) are used from the beginning of treatment 1, 3

Clinical Evidence on Dosing and Sedation

The recommended starting dose is 15mg once daily at bedtime, not 7.5mg 4, 2:

• The effective dosage range is 15-45mg daily, with 7.5mg considered subtherapeutic 4, 2

• Pharmacokinetic studies show dose-proportional plasma concentrations: 15mg produces mean levels of 7.3±3.2 ng/mL, 30mg produces 18±7 ng/mL, and 45mg produces 28±12 ng/mL 4

• Maximum recommended dose is 30-45mg daily 4, 5

What to Expect When Increasing from 7.5mg to 15mg

Sleep benefits are maintained or improved 6, 5:

• The National Comprehensive Cancer Network recommends mirtazapine as particularly effective for patients with both depression and insomnia, without dose-specific restrictions for sleep benefits 6, 5

• Mirtazapine improves sleep disturbances and anxiety symptoms, often within the first week of treatment at therapeutic doses 2, 3

• The drug is specifically noted as "potent and well tolerated; promotes sleep, appetite, and weight gain" at the standard 7.5-30mg bedtime dosing range 4

Important Clinical Caveats

If insomnia emerges after dose increase, consider alternative explanations 6:

• Inadequate treatment of underlying depression (which commonly causes insomnia) may be the actual culprit 6

• Concurrent medication changes should be evaluated 6

• Worsening obstructive sleep apnea if present—mirtazapine may worsen this condition regardless of dose 6

Common side effects to monitor 5, 7:

• Increased appetite and weight gain (more common than with placebo) 2, 3
• Dry mouth 5
• Transient somnolence (actually decreases at higher therapeutic doses) 1, 3

Practical Dosing Algorithm

1. Start at 15mg at bedtime (not 7.5mg) for most patients 4, 2

2. Assess response within 1-2 weeks of any dose modification 6, 5

3. If inadequate response at 6-8 weeks, increase to 30mg, then potentially to 45mg maximum 4, 5, 2

4. Continue effective dose for 4-9 months after satisfactory response in first-episode depression 5