From the Guidelines
True, mirtazapine typically becomes less sedating at doses above 30mg. This is because at lower doses (7.5-15mg), mirtazapine strongly blocks histamine H1 receptors, which produces significant sedation, as seen in the dosing guidelines for mirtazapine, which recommends a starting dose of 7.5 mg at bedtime and a maximum dose of 30 mg at bedtime for potent sedation and promotion of sleep, appetite, and weight gain 1. As the dose increases to 30mg and beyond, the medication begins to block serotonin 5-HT2 and 5-HT3 receptors more effectively while also increasing norepinephrine activity, which counteracts some of the sedating properties, making higher doses less sedating than lower ones.
Some key points to consider when prescribing mirtazapine include:
- Starting dose: 7.5-15 mg at bedtime for sedation
- Maximum dose: 30-45 mg at bedtime for antidepressant efficacy with less sedation
- Common side effects: sleep disorders, constipation or diarrhea, anxiety, increased appetite and weight gain, nausea, headache, fatigue 1
- Clinicians often prescribe lower doses specifically for sleep or when sedation is desired, while higher doses are typically used when the primary goal is antidepressant efficacy with less sedation.
It's essential to understand the dose-dependent effects of mirtazapine to manage patient expectations and optimize treatment outcomes, particularly in terms of sedation and antidepressant efficacy, which can impact morbidity, mortality, and quality of life.
From the Research
Mirtazapine Sedative Effects
- The statement that mirtazapine starts losing sedative effects when over 30mg is partially supported by the available evidence 2.
- A study on rats found that a 30 mg/kg dose of mirtazapine produced sedation within minutes, but only in the first few days of administration, suggesting that sedative effects may be temporary and decrease with continued use 2.
- However, the study does not provide a clear answer to the question of whether mirtazapine loses sedative effects when the dose is over 30mg in humans.
- Another study found that low doses of mirtazapine (7.5-15 mg/day) are often used for management of insomnia, suggesting that sedative effects may be present at lower doses 3.
- A review of mirtazapine's pharmacology and therapeutic potential found that the drug produces fewer anticholinergic-, adrenergic- and serotonergic-related adverse events than tricyclic antidepressants, but may cause drowsiness and excessive sedation, especially at higher doses 4.
- An exploratory analysis of the relationship between mirtazapine dose and incidence of adrenergic side effects found no significant increase in risk of noradrenergic side effects with higher doses 5.