Mirtazapine

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What is Mirtazapine?

Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) used to treat major depressive disorder. Rather than blocking reuptake transporters like SSRIs and SNRIs, it works by blocking presynaptic alpha-2 autoreceptors and heteroreceptors, increasing the release of both norepinephrine and serotonin. It also blocks specific serotonin receptors (5-HT2 and 5-HT3) and histamine H1 receptors, which accounts for its strong sedating and appetite-stimulating effects. Mirtazapine is taken once daily at bedtime, and its sedation and appetite effects can be clinically useful for people with insomnia and weight loss accompanying depression.

Alpha-2 receptor blockade

Blocks presynaptic alpha-2 autoreceptors and heteroreceptors, removing the brake on norepinephrine and serotonin release, increasing the output of both neurotransmitters through a disinhibition mechanism distinct from reuptake inhibition

Sedation and appetite stimulation

Potent H1 histamine blockade produces significant sedation, while 5-HT2C receptor antagonism stimulates appetite — side effects that become therapeutic advantages for people experiencing depression alongside insomnia and unintentional weight loss

5-HT3 blockade antiemetic benefit

Blocking 5-HT3 receptors reduces nausea, a notable advantage over SSRIs and SNRIs that often cause GI side effects

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