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Mirtazapine

Remeron · Mirataz

Noradrenergic and Specific Serotonergic AntidepressantGeneric availableTDM data

The mechanism of action of mirtazapine for the treatment of major depressive disorder, is unclear. However, its efficacy could be mediated through its activity as an antagonist at central presynaptic α 2 -adrenergic inhibitory autoreceptors and heteroreceptors and enhancing central noradrenergic and serotonergic activity.

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FDA-Approved Indications

  • Major depressive disorder (adults)

Common Off-Label Uses

  • Insomnia
  • Appetite stimulation/weight gain
  • Nausea (chemotherapy or other)
  • PTSD nightmares
  • Generalized anxiety disorder

What Sets This Drug Apart

  • Unique NaSSA mechanism (NOT a reuptake inhibitor): alpha-2 antagonism enhances norepinephrine/serotonin release; 5-HT2A/2C/3 antagonism shapes receptor selectivity
  • Dose-paradox: lower doses (7.5-15 mg) are MORE sedating than higher doses (30-45 mg) because noradrenergic activation outweighs H1 histamine blockade at higher doses
  • Most sedating non-TCA antidepressant (potent H1 antagonism at lower doses); therapeutically useful for insomnia but limiting for daytime function
  • Significant weight gain and appetite stimulation; sometimes used therapeutically in underweight or anorexic patients
  • Minimal sexual dysfunction compared to SSRIs/SNRIs — an important switch option when sexual side effects are intolerable
  • No meaningful CYP inhibition despite being a multi-CYP substrate (1A2, 2D6, 3A4); low drug interaction potential as a perpetrator
Boxed Warning
SUICIDAL THOUGHTS AND BEHAVIORS