Mirtazapine is a hardworking drug with multiple side-gigs ! It’s a anti-depressant that is also commonly used off-label as a sleep medication but can also stimulate appetite and cause weight gain ( Remeron being a common brand here in USA) . As far as sleep goes, it does a funny, unique thing – or at least it’s supposed to !! Ordinarily you expect a stronger sedating effect on increasing doses of a sleep medication, but Mirtazapine likes it complicated. At doses under 15mg , the sedating effects predominate but at doses of 30 mg and above, it has more of anti-depressant effect while losing the sedating effect . The reason in theory has to do with the many receptors that Mirtazapine likes to hang out with. At lower doses it has just enough strength to attach to Histamine receptors in the brain and gives you anti-histamine sedation, but higher doses it causes release of Serotonin, Dopamine and Norepinephrine. This witches brew apparently makes you happier but then also more active & less sleepy … or at least it’s supposed to !!
Now I keep saying that annoying “at least it’s supposed to”, because this dose dependent sleep effect business is not very well studied in large numbers yet. A small study in 2005 showed the sedative effect is gone after a week even in lower doses, while an indirect, retrospective study published in 2019 did not find insomnia in doses higher than 30 mg, although it did show higher tachycardia incidence. So for sleep effects, you need to remember the Goldilocks principle – just the right dose, too low and patient gets no sleep, too high and patient still gets no sleep – but just the right dose might have them sleeping like a bear hibernating in winter 😉 hopefully more than just a week !
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