What type of medication is mirtazapine?

Mirtazapine Classification and Mechanism of Action

Mirtazapine is a tetracyclic antidepressant classified as a Noradrenergic and Specific Serotonergic Antidepressant (NaSSA) that works by blocking presynaptic alpha-2 adrenergic receptors and postsynaptic serotonin type 2 and type 3 receptors. 1

Pharmacological Classification and Mechanism

Mirtazapine has a unique pharmacological profile that distinguishes it from other antidepressant classes:

• Primary classification: Noradrenergic and Specific Serotonergic Antidepressant (NaSSA) 2
• Chemical structure: Tetracyclic compound belonging to the piperazino-azepine group 3
• Receptor activity:
  • Blocks presynaptic alpha-2 adrenergic auto- and heteroreceptors 4
  • Antagonizes postsynaptic serotonin 5-HT2 and 5-HT3 receptors 5
  • Has weak affinity for 5-HT1 receptors 5
  • Has histamine (H1) antagonist properties (particularly at lower doses) 5
  • Has very weak muscarinic anticholinergic activity 5

Differentiation from Other Antidepressant Classes

Mirtazapine differs from other common antidepressant classes:

• Unlike SSRIs/SNRIs, mirtazapine does not inhibit the reuptake of serotonin or norepinephrine 4
• Unlike tricyclic antidepressants (TCAs), mirtazapine has fewer anticholinergic side effects 2
• Unlike MAOIs, mirtazapine does not inhibit monoamine oxidase enzymes 3

FDA-Approved Indication

Mirtazapine is FDA-approved for the treatment of Major Depressive Disorder (MDD) in adults 3. According to the American College of Physicians guideline, it is considered a second-generation antidepressant 6.

Clinical Applications

While primarily indicated for depression, mirtazapine has several characteristics that make it useful in specific clinical scenarios:

• Faster onset of action: Evidence suggests mirtazapine may work more quickly than some SSRIs 2
• Beneficial for sleep disturbances: Its sedative properties make it useful for patients with depression and insomnia 5
• Anxiolytic effects: Shows effectiveness for anxiety symptoms accompanying depression 1
• Less sexual dysfunction: Unlike many other antidepressants, mirtazapine is not commonly associated with sexual dysfunction 5

Common Side Effects

The most frequently reported adverse effects include:

• Somnolence (particularly at lower doses) 5
• Increased appetite 3
• Weight gain 3
• Dizziness 1

Dosing Considerations

• Starting dose: 15 mg/day administered as a single dose at bedtime 1
• Maintenance dose: Can be titrated up to 30-45 mg/day based on clinical response 4
• Pharmacokinetics: Rapid absorption, extensive hepatic metabolism, elimination half-life of approximately 22 hours allowing for once-daily dosing 4

Important Precautions

• Contraindicated with MAOIs (including 14 days after discontinuing MAOIs) 3
• Carries a black box warning regarding increased risk of suicidal thoughts and behaviors in young adults 3
• Rare but serious adverse effects include agranulocytosis and neutropenia 4

Mirtazapine's unique mechanism of action and side effect profile make it a valuable option for treating depression, particularly in patients who may benefit from its sedative properties or who experience intolerable side effects with other antidepressants.