II. Indications

  1. Major Depression
    1. Unresponsive to other Antidepressants
    2. Comorbid Anxiety Disorder
    3. Comorbid Insomnia
  2. Other indications
    1. Cachectic or chronically ill patients
    2. Antipsychotic induced Akathisia

III. Mechanism

  1. Tetracyclic piperazinoazepine
  2. Norepinephrine Antagonist Serotonin Antagonist
    1. Blocks Pre-synaptic Alpha 2 Adrenergic Receptors
      1. Enhances central noradrenergic activity
    2. Blocks Post-synaptic 5-HT2, 5-HT3 Serotonin Receptors
      1. Enhances central Serotoninergic activity at 5-HT-1
  3. Significant Antihistamine activity
    1. Dose dependent effect
      1. Dose 15 mg: Antihistamine effects predominate
      2. Dose 45 mg: Noradrenergic effects predominate
    2. Antihistamine Symptoms
      1. Weight gain
      2. Sedation

IV. Pharmacokinetics

  1. Half-Life: 20 to 40 hours
  2. Primarily Hepatic metabolism

V. Dosing

  1. Major Depression
    1. Start: 15 mg orally at bedtime
    2. May titrate dose every 1-2 weeks
    3. Effective dose: 15 to 30 mg orally at bedtime (maximum dose 45 mg/day)
  2. Antipsychotic induced Akathisia
    1. Dose: 15 mg orally daily each morning

VI. Efficacy: Effective in treating Major Depression

  1. Superior to Placebo
  2. As effective as Elavil, Desyrel, and Prozac

VII. Adverse Effects

  1. Somnolence (54%)
    1. Consider dosing at bedtime to improve sleep
  2. Dry Mouth (25%)
  3. Increased appetite (17%)
  4. Weight gain (12%) may be significant
  5. Dizziness (7%)
  6. Agranulocytosis (0.1% cases)

VIII. Precautions

  1. Agranulocytosis (occurs in 0.1% cases)
    1. Similar Incidence to other Antidepressants
    2. Does not warrant routine CBC monitoring
  2. Do not use within 14 days of MAO Inhibitor
  3. Serotonin Syndrome risk
  4. Do not use with drugs causing excessive sedation
    1. Alcohol
    2. Benzodiazepines

IX. Advantages

  1. No cardiac effects
  2. No or minimal Orthostatic Hypotension
  3. Low incidence Antidepressant Induced Sexual Dysfunction
  4. No deaths have occurred in overdosage
  5. Available as a solutab (dissolves)

X. Safety

  1. Pregnancy Category C
  2. Unknown safety in Lactation

XI. Drug Interactions

  1. Minimal Cytochrome P450 inhibition

XIII. References

  1. (2023) Med Lett Drugs Ther 62(1592): 25-32
  2. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 38-9
  3. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  4. Burrows (1997) Psychopharmacol 17:34S-39S [PubMed]
  5. Hartmann (1999) Am Fam Physician 59(1): 159-61 [PubMed]
  6. Majeroni (1998) J Am Board Fam Pract 11:127-39 [PubMed]

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Related Studies

Cost: Medications

mirtazapine (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
MIRTAZAPINE 15 MG ODT Generic $0.47 each
MIRTAZAPINE 15 MG TABLET Generic $0.07 each
MIRTAZAPINE 30 MG ODT Generic $0.47 each
MIRTAZAPINE 30 MG TABLET Generic $0.09 each
MIRTAZAPINE 45 MG ODT Generic $0.68 each
MIRTAZAPINE 45 MG TABLET Generic $0.13 each
MIRTAZAPINE 7.5 MG TABLET Generic $0.74 each

Ontology: Mirtazapine (C0049506)

Definition (NCI_NCI-GLOSS) A drug used to treat depression. It belongs to the family of drugs called antidepressant agents.
Definition (NCI) A synthetic tetracyclic derivative of the piperazino-azepines with antidepressant activity. Although its mechanism of action is unknown, mirtazapine enhances central adrenergic and serotonergic transmission, possibly by acting as an antagonist at central presynaptic alpha 2 adrenergic inhibitory autoreceptors and heteroreceptors. This agent is a potent antagonist of 5-hydroxytryptamine type 2 (5-HT2), 5-HT3, and histamine 1 (H1) receptors, and a moderate antagonist of peripheral alpha 1 adrenergic and muscarinic receptors.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C035133
SnomedCT 108430001, 386847004
LNC LP19150-9, MTHU007402
English 6-azamianserin, Pyrazino(2,1-a)pyrido(2,3-c)(2)benzazepine, 1,2,3,4,10,14b-hexahydro-2-methyl-, mirtazapine, MIRTAZAPINE, Mirtazapine, mirtazapine (medication), mirtazapine [Chemical/Ingredient], Mirtazapine (product), Mirtazapine (substance)
Spanish mirtazapina (producto), mirtazapina (sustancia), mirtazapina

Ontology: Remeron (C0525726)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C035133
English Remeron, zispin, remeron, Zispin, Celltech brand of mirtazapine, Norset, Organon brand of mirtazapine, Remergil