Prescription ·Strong evidence ·Reviewed May 2026
Prescription noradrenergic and specific serotonergic antidepressant (NaSSA) approved for major depressive disorder. Known for its sedating and appetite-stimulating properties, which can be therapeutically useful in patients with insomnia and poor appetite or weight loss. At lower doses, sedation is more prominent due to stronger histamine H1 blockade; at higher doses, noradrenergic activation can offset sedation. Dosage must be determined by your prescribing physician.
The bottom line
Evidence rating strong. Most-documented uses: depression symptom relief, sleep improvement, appetite stimulation. 10 sources indexed (2015–2026), with 1 interaction record on file.
Core mechanism
Antagonizes central presynaptic alpha-2 adrenergic receptors, enhancing norepinephrine and serotonin release. Also blocks serotonin 5-HT2A, 5-HT2C, and 5-HT3 receptors, directing serotonin activity toward 5-HT1A receptors. Potent histamine H1 receptor antagonist (contributing to sedation and weight gain) with minimal anticholinergic activity.
Can be taken with or without food. Typically administered at bedtime due to sedating effects. Orally disintegrating tablets dissolve on the tongue without water.3
Nutrients this medication can lower over time, and what to replace.
Antidepressant-associated SIADH can increase renal free-water retention and dilute serum sodium, producing hyponatremia.
Mirtazapine enhances serotonergic and noradrenergic transmission through alpha-2 antagonism. Adding 5-HTP increases serotonin production, creating risk of serotonin excess.
Recommendation: Avoid combining 5-HTP with mirtazapine. While mirtazapine's mechanism differs from SSRIs, the serotonergic enhancement is still significant.
Numbered references. Citations throughout the page link here.
Ostenfeld A, Lyngholm S, Christensen SE et al.. Mirtazapine in pregnancy and lactation: A systematic review of adverse outcomes. Acta psychiatrica Scandinavica. 2025
Milosavljević MN, Janković SM, Kostić MJ et al.. Mirtazapine-induced Acute Pancreatitis in Patients With Depression: A Systematic Review. Journal of psychiatric practice. 2023
Furukawa TA, Cipriani A, Cowen PJ et al.. Optimal dose of selective serotonin reuptake inhibitors, venlafaxine, and mirtazapine in major depression: a systematic review and dose-response meta-analysis. The lancet. Psychiatry. 2019
Ottman AA, Warner CB, Brown JN. The role of mirtazapine in patients with fibromyalgia: a systematic review. Rheumatology international. 2018
Smit M, Dolman KM, Honig A. Mirtazapine in pregnancy and lactation - A systematic review. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2016
Vidal C, Reese C, Fischer BA et al.. Meta-Analysis of Efficacy of Mirtazapine as an Adjunctive Treatment of Negative Symptoms in Schizophrenia. Clinical schizophrenia & related psychoses. 2015
Ostenfeld A, Carlsen SE, Jensen AK et al.. Mirtazapine or ondansetron for hyperemesis gravidarum: a randomized placebo-controlled trial. American journal of obstetrics and gynecology. 2026
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