What class of drug is mirtazapine?

Mirtazapine Drug Classification

Mirtazapine is a tetracyclic antidepressant belonging to the noradrenergic and specific serotonergic antidepressant (NaSSA) class. 1, 2, 3

Pharmacological Classification Details

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

• Chemical Structure: Tetracyclic compound with the chemical designation 1,2,3,4,10,14b-hexahydro-2-methylpyrazino[2,1-a]pyrido[2,3-c]2benzazepine 1
• Mechanism of Action:
  • Increases noradrenergic and serotonergic neurotransmission via blockade of central α2-adrenergic auto- and heteroreceptors 2
  • Directly blocks 5-HT2 and 5-HT3 receptors 2
  • Enhances 5-HT1 receptor-mediated neurotransmission 2

Classification in Clinical Guidelines

The American College of Physicians classifies mirtazapine as a second-generation antidepressant 4, 5. Within this broader category, it is specifically recognized as a serotonin norepinephrine reuptake inhibitor (SNRI) in some contexts 4.

However, it's important to note that while sometimes grouped with SNRIs for clinical purposes, mirtazapine's mechanism differs from traditional SNRIs:

• Unlike typical SNRIs, mirtazapine does not inhibit serotonin or norepinephrine reuptake 2
• It acts through receptor antagonism rather than reuptake inhibition 2, 6

Clinical Distinctions from Other Antidepressant Classes

Mirtazapine differs from other antidepressant classes in several important ways:

• Versus SSRIs: Mirtazapine has a faster onset of action (potentially within 1-2 weeks) compared to SSRIs 7
• Versus Tricyclic Antidepressants (TCAs): Mirtazapine has fewer anticholinergic, adrenergic, and cardiovascular side effects than TCAs 2, 6
• Versus Monoamine Oxidase Inhibitors (MAOIs): MAOIs have significant cardiovascular side effects and should be avoided in cardiovascular disease, while mirtazapine has been shown to be safe in this population 4

Clinical Relevance of Classification

The NaSSA classification of mirtazapine explains its unique clinical profile:

• Sedation: High affinity for histamine H1 receptors explains its sedative properties, making it useful for depression with insomnia 4, 6
• Appetite stimulation: Can be beneficial in patients with depression and weight loss 4, 3
• Low sexual dysfunction: Unlike SSRIs, mirtazapine has minimal sexual side effects 3
• Cardiovascular safety: Generally well-tolerated in patients with cardiovascular disease 4

Understanding mirtazapine's classification as a NaSSA helps clinicians leverage its unique receptor profile for specific patient populations, particularly those with insomnia, anxiety, or poor tolerance of other antidepressant classes.