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Why does Mirtazapine cause Restless Legs Syndrome?


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Why does Mirtazapine cause Restless Legs Syndrome? Mirtazapine is known to often provoke restless legs syndrome (RLS). Mirtazapine has an approximate 30% chance of inducing it; by comparison, paroxetine, sertraline, and other psychiatric medications only have an approximate 5% chance of causing RLS symptoms.

Why is Mirtazapine prone to causing RLS?

It's very interesting, especially that high percentage. No one seems to know why. They say that it might be due to its strong antihistamine properties. Some experts have proposed that it is due to its 5HT2 antagonist properties. But then other strong antihistamines and 5HT2 antagonists should also be prone to cause RLS, e.g. Amitriptyline, Nortriptyline, Doxepine etc., but they don't seem to cause it as frequently as Mirtazapine. One could argue that it is due to anticholinergic properties, which might have a counterbalancing effect.

Some say that it may be Mirtazapine's pro-noradrenergic properties, but shouldn't we see it with other NRIs and pro-noradrenergic drugs? Many questions, no definitive answers...

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