What is the recommended dosing of mirtazapine (Remeron) for optimal sleep?

Mirtazapine Dosing for Optimal Sleep

For optimal sleep effects, mirtazapine should be started at 7.5-15 mg taken once daily at bedtime, with lower doses (7.5 mg) generally being more sedating than higher doses. 1, 2

Mechanism of Action for Sleep

Mirtazapine's sleep-promoting effects are primarily due to:

• Potent antagonism of histamine H1 receptors (causing sedation)
• Blockade of serotonin 5-HT2 and 5-HT3 receptors (reducing insomnia and anxiety)
• Alpha-2 adrenergic receptor antagonism (enhancing noradrenergic and serotonergic transmission) 2, 3

Dosing Algorithm for Sleep

1. Initial dose: 7.5 mg (half of a 15 mg tablet) at bedtime 1, 4

   • This lower dose typically produces more sedation than higher doses due to the predominance of H1 receptor blockade
   • FDA-approved starting dose is 15 mg, but lower doses are commonly used off-label for insomnia 1

2. Dose adjustment:

   • If 7.5 mg is ineffective after 1-2 weeks, increase to 15 mg at bedtime
   • Paradoxically, increasing beyond 15 mg may reduce sedative effects as noradrenergic effects become more prominent at higher doses 2, 4
   • Maximum dose should not exceed 45 mg per day 1

3. Timing: Administer consistently each night, preferably 30-60 minutes before desired sleep time 1, 4

Clinical Evidence

• In clinical studies, mirtazapine has demonstrated effectiveness for sleep disturbances with improvements noted in:

  • Sleep onset
  • Sleep duration
  • Sleep quality 4

• A fixed dosing regimen of mirtazapine at bedtime has shown greater effects on sleep compared to ascending dose regimens 4

• Sleep improvements may be observed within the first week of treatment, while antidepressant effects typically take 2-4 weeks 2

Important Considerations

• Sedation profile: Sedation is most prominent at lower doses (7.5-15 mg) and may decrease at higher doses (30-45 mg) as noradrenergic effects become more prominent 2, 3

• Side effects to monitor:

  • Increased appetite and weight gain (10% vs 1% with placebo) 3
  • Morning drowsiness/hangover effects
  • Dry mouth (25% vs 16% with placebo) 3

• Advantages over other sleep medications:

  • No significant risk of respiratory depression
  • Minimal risk of dependence or withdrawal
  • May be especially beneficial in patients with comorbid depression and anorexia 5

• Cautions:

  • Elderly patients may require lower starting doses (7.5 mg)
  • Monitor for rare but serious adverse effects such as agranulocytosis 3
  • Screen for bipolar disorder before initiating treatment 1

Comparison to Other Sleep Medications

The American Academy of Sleep Medicine does not specifically recommend mirtazapine for insomnia in their clinical practice guidelines, though it is commonly used off-label 5. For primary insomnia, they suggest:

• Suvorexant, eszopiclone, zolpidem, or doxepin for sleep maintenance insomnia
• Zaleplon, zolpidem, or ramelteon for sleep onset insomnia 5

However, mirtazapine may be particularly useful when insomnia co-occurs with depression, anxiety, or poor appetite 5.