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Mirtazapine

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Mirtazapine, Remeron, Norepinephrine Antagonist Serotonin Antagonist

  • 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
  • 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
  • Pharmacokinetics
  1. Half-Life: 20 to 40 hours
  2. Primarily Hepatic metabolism
  • 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
  1. Superior to Placebo
  2. As effective as Elavil, Desyrel, and Prozac
  • 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)
  • 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
  • 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)
  • Safety
  1. Pregnancy Category C
  2. Unknown safety in Lactation
  • Drug Interactions
  1. Minimal Cytochrome P450 inhibition
  • Resources
  1. Mirtazapine (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=f23631be-c7ae-46e9-b771-a70be17bc9f0
  • 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]