What is mirtazapine?

From the Guidelines

Mirtazapine is an atypical antidepressant that has been shown to be safe and offers additional benefits, including appetite stimulation, and may be used for sleep, as noted in a recent study published in Circulation in 2024 1.

Key Points About Mirtazapine

• Mirtazapine belongs to the class of drugs called tetracyclic antidepressants and works by increasing the levels of norepinephrine and serotonin in the brain, which helps improve mood.
• It is typically taken once daily at bedtime, with starting doses usually at 15 mg and potentially increasing to 30-45 mg based on response and tolerability.
• The medication is known for its sedative effects, making it particularly helpful for patients with depression who also experience insomnia or appetite loss.
• Common side effects include drowsiness, increased appetite, weight gain, and dry mouth.
• These sedative effects tend to be more pronounced at lower doses (15 mg) and may actually decrease at higher doses.
• Patients should be aware that mirtazapine may take 2-4 weeks to show full therapeutic effects, and the medication should not be stopped abruptly but rather tapered off under medical supervision.
• It should be used cautiously in elderly patients and those with liver or kidney problems, and alcohol should be avoided while taking this medication.

Considerations for Use

• According to the study published in Circulation in 2024 1, mirtazapine has been shown to be safe, but its efficacy in treating depression in patients with cardiovascular disease has not been assessed.
• Cognitive behavioral therapy for insomnia is recommended as first-line treatment before the initiation of sedating antidepressants like mirtazapine 1.
• The American College of Physicians recommends that when clinicians choose pharmacologic therapy to treat patients with acute major depression, they select second-generation antidepressants, including mirtazapine, on the basis of adverse effect profiles, cost, and patient preferences 1.

From the FDA Drug Label

Mirtazapine tablets contain mirtazapine. Mirtazapine has a tetracyclic chemical structure and belongs to the piperazino-azepine group of compounds. Mirtazapine is a white to creamy white crystalline powder which is practically insoluble in water.

Mirtazapine is an antidepressant medication, specifically a tetracyclic compound belonging to the piperazino-azepine group of compounds, used for the treatment of major depressive disorder (MDD) in adults 2.

• It has the empirical formula of C17H19N3 and a molecular weight of 265.35.
• Mirtazapine is available as oral tablets containing 15 or 30 mg of the active ingredient 2.

From the Research

What is Mirtazapine

• Mirtazapine is a presynaptic alpha-2 antagonist that has dual action by increasing noradrenergic and serotonergic neurotransmission 3.
• It is a noradrenergic and specific serotonergic antidepressant (NaSSA) that is approved in many countries for use in the treatment of major depression 4.
• Mirtazapine has a unique pharmacodynamic profile, which includes the enhancement of serotonergic neurotransmission specifically mediated via 5-HT1 receptors, and it is a postsynaptic serotonergic 5-HT2 and 5-HT3 antagonist 3.

Mechanism of Action

• The enhancement of serotonergic neurotransmission is specifically mediated via 5-HT1 receptors because mirtazapine is a postsynaptic serotonergic 5-HT2 and 5-HT3 antagonist 3.
• Mirtazapine has only a weak affinity for 5-HT1 receptors and has very weak muscarinic anticholinergic and histamine (H1) antagonist properties 3.
• Mirtazapine lacks auto-induction of hepatic isoenzymes, and although it is a substrate of P450 isoenzymes 1A2, 2D6, and 3A4, in vitro studies show that it is not a potent inhibitor or inducer of any of these enzymes 3.

Efficacy and Tolerability

• Mirtazapine is an effective, safe, and well-tolerated addition to the antidepressant armamentarium 3.
• Controlled clinical trials involving almost 2800 mirtazapine-treated patients have demonstrated the compound to be effective for the treatment of moderate-to-severe major depression 3.
• Mirtazapine has shown a rapid onset of action in patients with predominantly severe depressive illness in a comparative study against fluoxetine 3.
• Transient somnolence, hyperphagia, and weight gain are the most commonly reported adverse events, which may be attributed to the antihistaminic (H1) activity of mirtazapine at low doses 3.

Clinical Applications

• Mirtazapine may also be effective in the treatment of anxiety disorders, obsessive-compulsive disorder, undifferentiated somatoform disorder, and, as add-on therapy, in schizophrenia 4.
• Mirtazapine appears to be an effective strategy for treating anxiety, agitation, and insomnia and for diminishing SSRI-related sexual dysfunction without compromising the patient's therapeutic response to the medication 5.
• The anxiolytic properties of mirtazapine may be due to its antagonism of 5-HT(2) receptors and can appear as early as the first week of treatment 5.