Mirtazapine (Remeron) is a noradrenergic and specific serotonergic (5-HT) antidepressant (NaSSA) with a relatively high response rate and low dropout rate (Cipriani et al, 2018). It is an antagonist at norepinephrine (alpha-2), 5-HT2, and 5-HT3 receptors. Mirtazapine is a suitable first-line antidepressant option for an underweight patient who can’t sleep. Mirtazapine has antiemetic properties thanks to 5-HT3 antagonism, which is the principal mechanism of action of ondansetron (Zofran).
Remeron is a potent antihistamine, leading to sedation and appetite stimulation. About half of patients gain significant weight. However, at higher doses, its noradrenergic characteristics outshine its antihistamine effects. Hence, at high doses mirtazapine can be less sedating and cause less appetite stimulation. This is an unusual property among psychotropics, also noted with the TCA doxepin (Sinequan).
Mirtazapine may work a bit faster than other antidepressants. The patient will “remember” the prescriber fondly for making them feel better quickly with Remeron, then not so fondly for making them fat. Consider using Remeron for an acute depressive episode, then changing to another antidepressant (or increasing the dose of mirtazapine) if the patient starts gaining weight.
“California Rocket Fuel” is a combination of mirtazapine with the SNRI venlafaxine (Effexor). This combo was previously felt to be exceptionally effective for depression due to complementary mechanisms of action. Unfortunately, mirtazapine augmentation was recently found to be no better than placebo for individuals who had failed antidepressant monotherapy (Navarro et al, 2019).
Mirtazapine is a third-line treatment for akathisia (behind propranolol and clonazepam) at 15 mg. At higher doses mirtazapine may exacerbate akathisia. Other side effects of mirtazapine include dry mouth and constipation. There is a risk of neutropenia, although rare.
Remeron does not inhibit sexual functioning, and can actually be used as an adjunct to reverse SSRI-induced sexual dysfunction.
Dosing: Start 15 mg HS; FDA maximum is 45 mg, but 60 mg is safe and may be more effective for depression. Note that mirtazapine causes less somnolence and less weight gain at higher doses. For treatment of akathisia, do not exceed 15 mg.