What are the contraindications for Mirtazapine (Remeron)?

Mirtazapine Contraindications

Mirtazapine is absolutely contraindicated in patients with known hypersensitivity to the drug and in those taking monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping MAOI therapy due to the risk of potentially fatal serotonin syndrome. 1

Absolute Contraindications

1. Hypersensitivity

   • Hypersensitivity to mirtazapine or any of its excipients 1

2. MAOI Therapy

   • Concurrent use with MAOIs intended to treat psychiatric disorders 1
   • Use within 14 days of stopping an MAOI intended to treat psychiatric disorders 1
   • Starting mirtazapine in patients being treated with other MAOI drugs such as:
     • Linezolid
     • Intravenous methylene blue 1

Relative Contraindications/Use with Caution

Cardiovascular Considerations

• QT Interval Prolongation

  • Mirtazapine can cause QT interval prolongation, potentially predisposing patients to ventricular tachycardia 2
  • Use with caution in patients with pre-existing cardiac conditions or those taking other QT-prolonging medications

• Hypertension

  • May cause hypertension, similar to MAOIs 2
  • Monitor blood pressure, especially when initiating therapy

Hematologic Considerations

• Agranulocytosis Risk
  • Rare but serious risk of agranulocytosis (absolute neutrophil count <500/mm³) 1
  • In premarketing trials, 2 out of 2796 patients developed agranulocytosis and a third developed severe neutropenia 1
  • Discontinue if patient develops sore throat, fever, stomatitis, or other signs of infection along with low WBC count 1

Neuropsychiatric Considerations

• Bipolar Disorder

  • Not approved for bipolar depression 1
  • Screen patients for bipolar disorder before initiating therapy to avoid precipitating mixed/manic episodes 1

• Suicidality

  • Risk of suicidal thinking and behavior, particularly in children, adolescents, and young adults 1
  • Monitor for worsening depression or emergence of suicidal ideation

Special Populations

• Pregnancy

  • Not recommended during pregnancy 2
  • Women of reproductive potential must use reliable contraception 2

• Nursing Mothers

  • Not recommended during nursing 2

• Hepatic/Renal Impairment

  • Clearance may be reduced in hepatic or renal impairment 3
  • Careful dosage titration and monitoring required 4

Drug Interactions to Avoid

1. Serotonergic Drugs (risk of serotonin syndrome)

   • Triptans
   • Tricyclic antidepressants
   • Fentanyl
   • Lithium
   • Tramadol
   • Tryptophan
   • Buspirone
   • St. John's Wort 1

2. CNS Depressants

   • Alcohol
   • Benzodiazepines
   • Other sedatives 4

Clinical Pitfalls and Caveats

1. Sedation Paradox

   • Increased sedation is more common at subtherapeutic doses 3
   • Using appropriate dosages (≥15 mg as a single evening dose) from the beginning may reduce sedation complaints 3

2. Weight Gain

   • Increased appetite (11% vs 2% with placebo) and weight gain (10% vs 1% with placebo) are common side effects 4
   • Consider alternative antidepressants in patients where weight gain would be problematic

3. Monitoring Requirements

   • Monitor for emergence of serotonin syndrome symptoms 1
   • Regular monitoring for suicidal thoughts, especially in younger patients 1
   • Monitor complete blood count if signs of infection develop 1

4. Discontinuation

   • Avoid abrupt discontinuation to prevent withdrawal symptoms 2

In cardiovascular disease patients, mirtazapine has been shown to be relatively safe compared to tricyclic antidepressants, which should be avoided in heart failure due to risk of orthostatic hypotension, worsening heart failure, and arrhythmias 2. However, careful monitoring is still required, particularly for QT interval prolongation and hypertension.