Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) used primarily for the treatment of major depressive disorder (MDD). It is a tetracyclic piperazinoazepine derivative that enhances central noradrenergic and serotonergic activity through antagonism of central alpha-2 adrenergic autoreceptors and heteroreceptors. Unlike SSRIs, it has minimal direct action on serotonin reuptake. In the Indian context, it is valued for its rapid onset of action on anxiety and sleep symptoms associated with depression, its appetite-stimulating effect, and a favorable side effect profile regarding sexual dysfunction.
Adult: Initial dose: 15 mg once daily, preferably at bedtime. Dose may be increased to 30 mg/day after 1-2 weeks based on response and tolerability. Maximum recommended dose: 45 mg/day.
Note: Administer orally, with or without food. The tablet should be swallowed whole with water. Bedtime administration is strongly recommended to mitigate daytime sedation and dizziness. Do not crush or chew.
Mirtazapine acts as a potent antagonist at central presynaptic alpha-2 adrenergic autoreceptors and heteroreceptors. Blockade of these inhibitory receptors increases the firing of noradrenergic neurons, leading to enhanced norepinephrine release. The increased norepinephrine stimulates alpha-1 adrenergic receptors on serotonergic neurons, which, coupled with mirtazapine's direct antagonism of inhibitory alpha-2 heteroreceptors on serotonin neurons, results in increased serotonin release. It is also a potent antagonist of histamine H1 receptors (causing sedation and weight gain) and a moderate antagonist of 5-HT2 and 5-HT3 receptors (which may contribute to its anxiolytic effect and lower incidence of nausea and sexual dysfunction).
Pregnancy: Pregnancy Category C (US FDA). Animal studies show evidence of fetal risk; no adequate, well-controlled studies in humans. Use only if potential benefit justifies potential risk to the fetus. Neonates exposed late in third trimester may develop withdrawal symptoms (hypotonia, tremor, jitteriness, respiratory distress) or persistent pulmonary hypertension (PPHN). Consult an obstetrician.
Driving: May impair alertness, judgment, and motor coordination, especially during initial treatment and dose escalation. Patients should be cautioned against driving or operating hazardous machinery until they are certain the medication does not affect them adversely.
| Monoamine Oxidase Inhibitors (MAOIs) - e.g., Phenelzine, Selegiline | Risk of serotonin syndrome (hyperthermia, rigidity, myoclonus, autonomic instability). | Contraindicated |
| Other CNS Depressants (Alcohol, Benzodiazepines, Opioids) | Additive sedation, impaired psychomotor performance, and respiratory depression. | Major |
| Strong CYP3A4 Inhibitors (e.g., Ketoconazole, Clarithromycin, Ritonavir) | Increased mirtazapine plasma levels, risk of enhanced side effects. | Moderate |
| Strong CYP3A4 Inducers (e.g., Carbamazepine, Phenytoin, Rifampicin) | Decreased mirtazapine plasma levels, potential loss of efficacy. | Moderate |
| Serotonergic Drugs (SSRIs, SNRIs, Tramadol, Linezolid, Triptans) | Increased risk of serotonin syndrome. | Moderate to Major |
Same composition (Mirtazapine (15mg)), different brands: