Mirtazapine enhances noradrenergic and serotonergic neurotransmission through:

1. Alpha-2 Adrenergic Receptor Antagonism: Blocks presynaptic alpha-2 autoreceptors (increasing norepinephrine release) and heteroreceptors (enhancing serotonin release).
2. Serotonin Receptor Blockade: Antagonizes 5-HT2 and 5-HT3 receptors, reducing anxiety and nausea while promoting sleep and appetite (Lippincott Textbook of Pharmacology).
   Unlike SSRIs/SNRIs, it has minimal impact on serotonin reuptake, lowering the risk of sexual dysfunction (Lange Basic & Clinical Pharmacology).

1. Major Depressive Disorder (MDD):
   • First-line treatment for depression, particularly in patients with insomnia or weight loss (BNF).
2. Generalized Anxiety Disorder (GAD):
   • Off-label use for anxiety due to its calming effects.
3. Insomnia and Appetite Stimulation:
   • Low-dose mirtazapine (7.5–15 mg) is used off-label for sleep disturbances and cachexia (Lange Basic & Clinical Pharmacology).

• Adults:
  • Initial Dose: 15 mg at bedtime, increased to 30–45 mg/day after 1–2 weeks (BNF).
  • Maximum Dose: 45 mg/day (higher doses rarely improve efficacy).
• Elderly/Hepatic Impairment:
  • Start at 7.5 mg at bedtime; titrate cautiously (Lippincott).

Key Note: Lower doses (≤15 mg) are more sedating, while higher doses (30–45 mg) prioritize noradrenergic effects.

• Common: Sedation, weight gain, increased appetite, dry mouth, dizziness (BNF).
• Serious:
  • Agranulocytosis: Rare but requires immediate discontinuation if fever/sore throat occurs.
  • Hyperlipidemia/Hypercholesterolemia: Monitor lipids in long-term use.
  • QT Prolongation: Risk at high doses or with predisposing conditions (Lange Basic & Clinical Pharmacology).

• Contraindications:
  • Hypersensitivity to mirtazapine.
  • Concurrent use of MAO inhibitors (BNF).
• Monitoring:
  • Weight, lipid profile, and liver function tests periodically.
  • Blood counts if signs of infection arise (Lippincott).
• Pregnancy/Lactation:
  • Category C: Use only if benefits outweigh fetal risks. Excreted in breast milk—use with caution (Lange Basic & Clinical Pharmacology).

• CNS Depressants (e.g., alcohol, benzodiazepines): Enhanced sedation.
• Serotonergic Drugs (e.g., SSRIs, tramadol): Increased serotonin syndrome risk.
• CYP450 Interactions:
  • Inhibitors (e.g., fluvoxamine): Raise mirtazapine levels.
  • Inducers (e.g., carbamazepine): Reduce efficacy (BNF).

• Generic Name: Mirtazapine.
• Brand Names: Remeron®, Zispin®, and others.
• Formulations:
  • Tablets: 15 mg, 30 mg, 45 mg.
  • Orally Disintegrating Tablets: 15 mg, 30 mg (BNF).