Mirtazapin G.L. (Mirtazapine)

Mirtazapine acts on central neurotransmitter pathways involved in mood regulation, primarily used for depressive disorders.

• Major depressive disorder: reduces depressive symptoms and improves mood in adult patients.
• Depressive episodes associated with major depressive disorder: enhances sleep quality, appetite and overall functional status.
• Treatment‑resistant depression (adjunctive use): may augment response when combined with other antidepressants under specialist supervision.

• Mirtazapine antagonizes central presynaptic α2‑adrenergic receptors, increasing the release of norepinephrine and serotonin. It also blocks postsynaptic 5‑HT2 and 5‑HT3 receptors and H1 histamine receptors, which together enhance noradrenergic and serotonergic neurotransmission while producing sedative and appetite‑stimulating effects. The combined receptor profile leads to a rapid onset of antidepressant activity and contributes to its characteristic side‑effect profile, such as sedation and weight gain.

Mirtazapine may cause a range of adverse reactions, varying from mild to serious.

Common Side Effects

• Drowsiness: persistent sleepiness or fatigue that may affect daily activities, especially during the initial weeks of therapy.
• Increased appetite and weight gain: notable rise in hunger leading to gradual weight increase, often accompanied by changes in food preferences.
• Dry mouth: reduced salivation causing discomfort, difficulty swallowing, and a dry sensation in the oral cavity.
• Constipation: slowed intestinal motility resulting in infrequent, hard stools and possible abdominal discomfort.

Serious or Rare Side Effects

• Agranulocytosis: a rare but severe drop in white blood cell count that can increase infection risk and requires immediate medical attention.
• Serotonin syndrome: potentially life‑threatening condition characterized by agitation, hyperthermia, tremor, and autonomic instability when combined with other serotonergic drugs.
• Suicidal thoughts or behavior: emergence or worsening of suicidal ideation, especially during early treatment or dosage changes, necessitating close monitoring.

When prescribing mirtazapine, clinicians should consider several precautionary measures to ensure safe use.

• Assess psychiatric history: monitor for worsening depression or emergence of suicidal ideation.
• Evaluate hepatic function: use with caution in patients with severe liver impairment.
• Caution in elderly: increased risk of sedation, falls and orthostatic hypotension.
• Avoid abrupt discontinuation: taper the dose to reduce the likelihood of withdrawal symptoms.
• Pregnancy and lactation: prescribe only if the potential benefit outweighs the unknown risk to the fetus or infant.
• Store at ambient temperature: keep in the original packaging, protect from moisture and light.

Mirtazapine can interact with other medicines, altering its effectiveness or safety profile.

Major Interactions (Avoid)

• Monoamine oxidase inhibitors (MAOIs): concurrent use may precipitate serotonin syndrome, a potentially fatal condition.
• Potent CYP2D6 inhibitors (e.g., fluoxetine, paroxetine): can raise mirtazapine plasma concentrations, increasing risk of adverse effects.
• Central nervous system depressants (e.g., benzodiazepines, alcohol): additive sedation and respiratory depression may occur.

Moderate Interactions (Monitor Closely)

• Other serotonergic agents (e.g., SSRIs, SNRIs, tramadol): monitor for signs of serotonin syndrome.
• Antihistamines: may enhance sedative effects, requiring dose adjustment.
• Warfarin: mirtazapine may affect INR values, necessitating regular coagulation monitoring.