Mirtazapine is considered a noradrenergic and specific serotonergic antidepressant. It’s one of a newer generation of medications used to treat major depression.
The mechanism is unique, and the noradrenergic effects are mediated by blockade of alpha-2 presynaptic receptors which results in an increase in norepinephrine. This is a negative feedback loop, which means norepinephrine in the synaptic cleft will bind to presynaptic alpha-2 receptors resulting in decreased norepinephrine release (hence the negative feedback). If we block the alpha-2 receptors preventing norepinephrine from binding it will allow more norepinephrine to be released. Essentially, we are taking the break off.
Mirtazapine is also a histamine H1 receptor blocker which is the reason for many of the side effects including sleepiness and weight gain.
The dose is usually 15 mg at bedtime and can be increased every 1-2 weeks to a maximum dose of 45 mg at bedtime. In some cases, doses of up to 90 mg at bedtime have been used.
If the goal is sedation and help with sleep a 15 mg tab can be broken in half to 7.5 mg which is more sedating than 15 mg. Sedation associated with the affinity for H1 receptors and typically experienced at dosages of 15 mg/day may be counteracted by an increasing noradrenergic neurotransmission at dosages of 30 mg/day. The main point is higher doses result in less sedation because of increased noradrenergic effects.
Be mindful of the propensity for weight gain with this medication. BMI and waits circumference should be monitored.
The most common side effect of mirtazapine is sleepiness (54%), dry mouth (25%), increased appetite (17%), constipation (13%), weight gain (12%), weakness, dizziness, and flu like syndrome.
This is a good choice for a depressed patient with difficulty sleeping, and poor appetite. It’s also a good choice for a patient who is concerned about sexual side effects. If a patient is concerned about weight gain and sleepiness this may not be the best medication for that person. It works well in combination with venlafaxine of desvenlafaxine. There is some evidence to support the use of mirtazapine in combination with haloperidol to treat the negative symptoms of schizophrenia.