Drug Guide
Mirtazapine
Classification
Therapeutic: Antidepressant
Pharmacological: Alpha-2 adrenergic antagonist, Noradrenergic and specific serotonergic antidepressant (NaSSA)
FDA Approved Indications
- Major depressive disorder (MDD)
Mechanism of Action
Mirtazapine works by antagonizing central presynaptic alpha-2 adrenergic receptors, which increases the release of norepinephrine and serotonin. It also antagonizes specific serotonin receptors (5-HT2 and 5-HT3) and histamine H1 receptors, contributing to its antidepressant effects and sedative properties.
Dosage and Administration
Adult: Initially 15 mg at bedtime, titrated up to 30-45 mg daily based on response and tolerability.
Pediatric: Not approved for pediatric use.
Geriatric: Start at lower doses due to increased sensitivity, usually 15 mg at bedtime.
Renal Impairment: Use caution; no specific dosage adjustment established, monitor closely.
Hepatic Impairment: Use caution; start at lower doses, monitor liver function.
Pharmacokinetics
Absorption: Well absorbed orally, food has minor effect on absorption.
Distribution: Widely distributed; approximately 85% protein-bound.
Metabolism: Extensively metabolized in the liver primarily via CYP2D6, CYP1A2, and CYP3A4 pathways.
Excretion: Metabolites excreted in urine and feces.
Half Life: Approximately 20-40 hours.
Contraindications
- Hypersensitivity to mirtazapine
Precautions
- Use cautiously in patients with a history of seizure disorders, bipolar disorder (risk of mania), or angle-closure glaucoma. Monitor for signs of depression or worsening mood, especially early in therapy. Use with caution in hepatic impairment.
Adverse Reactions - Common
- Drowsiness or sedation (Common)
- Increase in appetite, weight gain (Common)
- Dizziness (Common)
- Dry mouth (Common)
Adverse Reactions - Serious
- Suicidal thoughts or behaviors (Serious, especially in young adults and adolescents)
- Blood dyscrasias, agranulocytosis (rare) (Rare)
- Serotonergic syndrome (when combined with other serotonergic agents) (Rare)
Drug-Drug Interactions
- MAO inhibitors (risk of serotonin syndrome), other CNS depressants, serotonergic drugs, CYP450 inhibitors or inducers
Drug-Food Interactions
- Alcohol may increase sedative effects.
Drug-Herb Interactions
N/ANursing Implications
Assessment: Monitor mood, suicidal ideation, and mental status. Assess weight and appetite. Check for allergic reactions and adverse effects.
Diagnoses:
- Risk for injury related to sedation or dizziness
- Imbalanced nutrition: less than body requirements related to nausea or decreased appetite
Implementation: Administer at bedtime to reduce daytime sedation. Monitor for therapeutic effects and adverse reactions. Educate patient about the onset of action (may take 1-4 weeks).
Evaluation: Assess improvement in depressive symptoms and monitor for adverse effects.
Patient/Family Teaching
- Instruct patient to take medication as prescribed, usually at bedtime.
- Warn about drowsiness and advise caution when driving or operating machinery.
- Advise to avoid alcohol and sedatives. Discuss potential weight gain and appetite changes.
- Report mood changes, suicidal thoughts, or adverse effects immediately.
Special Considerations
Black Box Warnings:
- Suicidality in young adults, especially during initial treatment
Genetic Factors: CYP2D6 poor metabolizers may have increased plasma levels.
Lab Test Interference: None established.
Overdose Management
Signs/Symptoms: Drowsiness, tachycardia, agitation, hallucinations, seizures, coma.
Treatment: Supportive care, gastric lavage if ingestion is recent, activated charcoal, and symptomatic treatment. Monitor cardiac status for arrhythmias.
Storage and Handling
Storage: Store at room temperature, 20-25°C (68-77°F), away from moisture and light.
Stability: Stable under recommended storage conditions for the duration of its shelf life.