Mirtazapine: An Antidepressant with Noradrenergic and Specific Serotonergic Effects

Abstract

Mirtazapine is a unique antidepressant that refines the specificity of effects on noradrenergic and serotonergic systems. It is an antagonist of presynaptic α2‐adrenergic autoreceptors and heteroreceptors on both norepinephrine and serotonin (5‐HT) presynaptic axons, plus is a potent antagonist of postsynaptic 5‐HT2 and 5‐HT3 receptors. The net outcome of these effects is increased noradrenergic activity together with specific increased serotonergic activity, especially at 5‐HT1A receptors. This mechanism of action maintains equivalent antidepressant efficacy but minimizes many of the adverse effects common to both tricyclic antidepressants and selective serotonin reuptake inhibitors. Mirtazapine has an onset of clinical effect in 2–4 weeks similar to other antidepressants, although sleep disturbances and anxiety symptoms may improve in the first week of treatment. It has minimal cardiovascular and anticholinergic effects, and essentially lacks serotonergic effects such as gastrointestinal symptoms, insomnia, and sexual dysfunction. Sedation, increased appetite, and weight gain are more common with mirtazapine than with placebo. An elimination half‐life of 20–40 hours enables once‐daily bedtime dosing. The recommended initial dosage is 15 mg once/day at bedtime, with an effective daily dosage range of 15–45 mg. Cases of overdose of up to 975 mg caused significant sedation but no cardiovascular or respiratory effects or seizures.

The Neurobiology of Sexual Function

“…For example, mirtazapine is a newly developed antidepressant that increases both serotonergic and noradrenergic activity and early reports suggest that rates of sexual dysfunction with mirtazapine are lower than placebo. 236 Similarly, some evidence suggests that yohimbine, a drug that increases NE activity, may be useful in treating erectile dysfunction and anorgasmia. [237][238][239] Studies suggest that NE is also active during the sexual response cycles of women.…”

Intolerance to Mirtazapine in Advanced Cancer

“…They concluded that lowdose ketamine is helpful and safe when added to opioid analgesia in postoperative patients. 4 In a second meta-analysis, Bell et al reported a similar role for ketamine in a postsurgical population. 5 Ketamine has been shown, anecdotally, to help manage a variety of adult opioid-refractory nonsurgical pains as well.…”

“…In addition, mirtazapine blocks presynaptic autoregulatory norepinephrine receptors that facilitate norepinephrine neurotransmission. 3,4 Mirtazapine has a rapid onset to activity relative to other antidepressants. 5,6 Rapid improvement of symptoms in individuals with a short survival time is important.…”

Appetite Stimulation After Surgery in a High Nutrition Risk Adolescent With Myotonic Dystrophy and Depression Case Report

“…In addition to its primary action, it is also a potent H1-histaminergic blocker, which can cause sedation, increased appetite, and weight gain. [21][22][23] Although weight gain may be an undesirable side effect in most patients, it is helpful in the treatment of certain groups of patients, as in this patient, whose underlying illness has led to poor appetite and unhealthy weight loss. Of note, the Food and Drug Administration has attached a black box warning to the use of mirtazapine as it has been associated with rare worsening depression and suicidal tendencies.…”