Mirtazapine is a tetracyclic antidepressant that belongs to the noradrenergic and specific serotonergic antidepressant (NaSSA) class. First introduced in the 1990s, it has become a widely used treatment for major depressive disorder (MDD) and other psychiatric conditions due to its unique receptor profile, effectiveness in improving both mood and sleep, and relatively low incidence of sexual side effects compared to selective serotonin reuptake inhibitors (SSRIs). Unlike SSRIs and SNRIs, which primarily target serotonin reuptake, mirtazapine works by antagonising central presynaptic alpha-2 adrenergic receptors, which increases the release of norepinephrine and serotonin. It also antagonises specific serotonin receptors (5-HT2 and 5-HT3) while enhancing transmission through 5-HT1A receptors, contributing to its antidepressant and anxiolytic properties. Additionally, potent antagonism at histamine H1 receptors explains its strong sedative effect, particularly at lower doses.
Clinically, mirtazapine is valued for its ability to reduce anxiety, improve sleep, stimulate appetite, and induce weight gain, making it especially suitable for patients with depression accompanied by insomnia, weight loss, or reduced appetite. Its sedative properties are most prominent at lower doses (15–30 mg), while higher doses (45 mg) are often less sedating due to reduced relative histamine receptor occupancy. This paradox is clinically important when tailoring therapy to patient needs. The drug’s favourable sexual side-effect profile also makes it an attractive alternative for patients intolerant to SSRIs or SNRIs.
Mirtazapine is generally well tolerated, but side effects such as weight gain, daytime sedation, and increased appetite are common. Rare but serious risks include agranulocytosis, serotonin syndrome when combined with serotonergic drugs, and worsening suicidal ideation in young adults. Because of its receptor actions, mirtazapine has been used off-label for a range of conditions, including generalised anxiety disorder, post-traumatic stress disorder, obsessive-compulsive disorder, and insomnia. It is available in standard tablets, orally disintegrating tablets (ODTs), and oral solutions in some markets.
Mirtazapine is taken once daily, usually at bedtime due to its sedating effect. Initial doses are commonly 15 mg, titrated up to 30–45 mg depending on clinical response and tolerability. Long-term maintenance therapy is often required in recurrent depression, guided by symptom control and side-effect burden.
Most side effects are dose-dependent and can often be managed by adjusting dosage, timing of administration, or supportive measures. Patients should not discontinue mirtazapine abruptly but should taper under medical supervision to avoid withdrawal symptoms such as anxiety, irritability, insomnia, or flu-like complaints.
Patients and families should be educated about warning signs, the importance of adherence, and when to seek urgent medical advice.
Mirtazapine is metabolised mainly via CYP1A2, CYP2D6, and CYP3A4 pathways. Important interactions include:
Patients should be encouraged to maintain an updated list of all medicines, vitamins, and supplements, and to share this with each healthcare provider to prevent dangerous interactions.
Overdose: Symptoms may include profound drowsiness, disorientation, confusion, tachycardia, hypotension, and in rare severe cases, seizures or cardiac arrhythmias. Fatal outcomes are rare with isolated overdose but possible in combination with other CNS depressants. Management is supportive, with monitoring of airway, breathing, circulation, and ECG. Activated charcoal may be considered if ingestion was recent.
Accidental double dose: Typically results in excess sedation or dizziness. Patients should avoid driving or operating heavy machinery and seek medical advice if symptoms persist or worsen.
Missed dose: Take as soon as remembered unless it is close to the next scheduled dose. Do not double doses. Consistent daily use is critical for antidepressant effectiveness.
Always read the medication guide and consult a healthcare provider for personalised dosing instructions. Sudden discontinuation should be avoided to prevent withdrawal symptoms.
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