Mirtazapine Tablets are indicated for the treatment of major depressive disorder (MDD).

Pharmacodynamics: The exact mechanism of action of Mirtazapine in major depressive disorder is not fully understood. It is believed to enhance central noradrenergic and serotonergic neurotransmission. Mirtazapine acts as an antagonist at central presynaptic α2-adrenergic autoreceptors and heteroreceptors, resulting in increased release of norepinephrine and serotonin. It is a potent antagonist of 5-HT2 and 5-HT3 receptors, with minimal affinity for 5-HT1 receptors. It also strongly blocks histamine (H1) receptors, which contributes to its sedative effect. In addition, it has moderate antagonistic activity at peripheral α1-adrenergic receptors, which may lead to orthostatic hypotension. Mild antimuscarinic activity is present, resulting in a low incidence of anticholinergic side effects.

Pharmacokinetics: After oral administration, Mirtazapine is rapidly absorbed, reaching peak plasma concentration in about 2 hours. It is approximately 85% bound to plasma proteins. The elimination half-life ranges from 20 to 40 hours (about 26 hours in males and 37 hours in females), supporting once-daily dosing. It shows linear pharmacokinetics within the therapeutic dose range.  Mirtazapine is extensively metabolized in the liver and eliminated via urine and feces within about four days. The main metabolic pathways are demethylation and oxidation followed by conjugation.

Adult dose: The recommended starting dose for Mirtazapine tablets is 15 mg/day, administered in a single dose, preferably in the evening or prior to sleep. The effective dose range was generally 15 to 45 mg/day and the patients not responding to the initial 15 mg dose may benefit from dose increases up to a 30 mg to maximum of 45 mg/day. Mirtazapine has an elimination half-life of approximately 20 to 40 hours; therefore, dose changes should be made at intervals of less than 1 to 2 weeks in order to allow sufficient time for the therapeutic response to a given dose.

Use in children: Use in children are not recommended to Mirtazapine.

Missed Dose: If anyone misses a dose of mirtazapine, take it as soon as remember unless it is close to when the next dose is due. If anyone missed a dose of medication and it is close to the time of next dose, skip the missed dose and should take next dose at the regularly scheduled time. One should not take double or more than prescribed dose.

Mirtazapine has clinically significant drug–drug interactions with monoamine oxidase inhibitors (MAOIs) and other serotonergic agents such as tryptophan, triptans, linezolid, SSRIs, venlafaxine, lithium, tramadol, and St. John’s wort. Concomitant use may increase the risk of serotonin-related effects. Mirtazapine may also affect the metabolism of carbamazepine, phenytoin, and cimetidine. Alcohol and diazepam should be avoided during treatment due to enhanced CNS depressant effects.

Mirtazapine is contraindicated in patients with known hypersensitivity to mirtazapine or any excipients.
Concomitant use with monoamine oxidase inhibitors (MAOIs) is contraindicated. Mirtazapine should not be used within 14 days of starting or stopping MAOI therapy.

Common side effects include dizziness, drowsiness, dry mouth, increased appetite, and weight gain.

Pregnancy Category C. Use during pregnancy only if clearly needed. Patients should inform their physician if they are pregnant, planning pregnancy, or breastfeeding.

Patients and caregivers should monitor for anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggression, impulsivity, akathisia, hypomania, mania, behavioral changes, worsening depression, and suicidal thoughts, especially during early treatment or dose adjustments. Risk of agranulocytosis should be considered. Mirtazapine may impair judgment, thinking, and motor coordination due to sedation. Significant elevation of liver enzymes (ALT ≥3 times normal) may occur.

Atypical antidepressants

Store below 30°C, protect from light and moisture. Keep out of reach of children.