Mirtazapine acts as an antagonist of alpha2 adrenergic presynaptic receptors, leading to an increase of 5HT and NA. This is the underlying mechanism of its antidepressant effect. But , its also a H1 antagonist with a strong affinity. So, it is used at a low dosage (15 mg) for its sedative effect.
It is described that, at higher dosage, this sedative effect is "lost".Why ? Is it because at 30-15mg, the increase of NA induce insomnia ? It could be a problem if you want to use the mirtazapine at an effective antidepressant dosage (30-45mg), and keep the benefit of this sleep inducer property....
Maybe this article can help you...
https://proceedings.med.ucla.edu/wp-content/uploads/2016/11/Dose-Dependent-Sedating-and-Stimulating-Effects-of-Mirtazapine.pdf
At low doses antihistaminic property is more pronounced and higher doses leads more noradrenergic activity,this is one of the important reason. But differential response for sedation is also noted for sleep inducing effects of Mirtazepine. At therapeutic doses benefit of sleep inducer property noted and few patient also reported daytime sedation with night dose of Mirtazepine.
Just a note - my gues is another factor s the histamine receptors in the brain get fully occupied when you go above 30 mg
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