Mirtaz7.5 mg

Mirtaz is an atypical antidepressant with the following evidence-based uses:

Established / FDA-approved use

• Major Depressive Disorder (MDD) in adults — Mirtaz is indicated for the treatment of major depressive disorder, based on controlled clinical trials in adult outpatients and inpatients meeting standard diagnostic criteria for depression.

Common off-label uses (not FDA-approved, but supported by clinical practice/limited evidence)

• Insomnia associated with depression, due to its sedating properties (usually at lower doses).
• Adjunct treatment for anxiety symptoms accompanying depression.
• Off-label use as an appetite stimulant in patients with poor appetite or unintended weight loss (e.g., in some cancer or elderly patients), based on its known side effect of increased appetite.
• Adjunctive use in treatment-resistant depression in combination with other antidepressants, under specialist supervision.

Use of Mirtaz for any indication should be individualized and supervised by a physician.

Each tablet contains Mirtazapine as the active ingredient. Mirtazapine is available as conventional film-coated tablets and orally disintegrating (dispersible) tablets, commonly in strengths of 7.5 mg, 15 mg, 30 mg, and 45 mg.

Mirtaz is an atypical antidepressant belonging to the class known as noradrenergic and specific serotonergic antidepressants (NaSSAs). Unlike selective serotonin reuptake inhibitors (SSRIs), Mirtaz does not primarily act by blocking neurotransmitter reuptake; instead it enhances central noradrenergic and serotonergic neurotransmission through receptor antagonism. It is commonly used for the treatment of major depressive disorder in adults and is notable for its sedating and appetite-stimulating side-effect profile, which is sometimes used to therapeutic advantage in patients with depression accompanied by insomnia or poor appetite.

Atypical antidepressant — Noradrenergic and Specific Serotonergic Antidepressant (NaSSA).

The precise mechanism of the antidepressant action of Mirtazapine is not fully established, but it is believed to enhance central noradrenergic and serotonergic activity through several receptor actions:

• Alpha-2 adrenergic antagonism: Mirtazapine blocks central presynaptic alpha-2 autoreceptors and heteroreceptors, which increases the release of norepinephrine and serotonin.
• 5-HT2 and 5-HT3 receptor antagonism: This shifts serotonergic transmission toward 5-HT1A receptor-mediated effects, thought to contribute to the antidepressant effect, and reduces nausea and sexual side effects compared with SSRIs.
• H1-histamine receptor antagonism: This is a potent effect responsible for the prominent sedative properties of Mirtazapine, especially at lower doses.

Mirtazapine has minimal effect on the reuptake of norepinephrine or serotonin and has negligible anticholinergic activity. It is well absorbed orally, extensively metabolized in the liver (via CYP1A2, CYP2D6, and CYP3A4), and has an elimination half-life of approximately 20–40 hours, allowing once-daily dosing.

Mirtaz tablets are usually taken once daily in the evening, preferably at bedtime, due to their sedating effect. Tablets may be taken with or without food. Orally disintegrating tablets should be placed on the tongue, allowed to dissolve, and swallowed without water (or with water if preferred), immediately upon removal from the blister pack. Conventional film-coated tablets should be swallowed whole with water. Do not chew film-coated tablets unless specifically formulated to be chewed. Take Mirtaz exactly as prescribed and do not adjust the dose or stop treatment without consulting a physician.

Mirtaz has the following clinically significant interactions:

• Monoamine oxidase inhibitors (MAOIs): Concurrent use, or use within 14 days of stopping an MAOI (or starting an MAOI within 14 days of stopping Mirtaz), is contraindicated due to risk of serious, potentially fatal reactions including serotonin syndrome (see Contraindications).
• Other serotonergic drugs (e.g., SSRIs, SNRIs, triptans, tramadol, other antidepressants): Concomitant use may increase the risk of serotonin syndrome; monitor closely for symptoms such as agitation, hallucinations, tachycardia, hyperthermia, and muscle rigidity.
• CNS depressants and alcohol: Mirtaz may enhance the sedative effects of benzodiazepines, other CNS depressants, and alcohol; concurrent use should be avoided or used with caution.
• Diazepam and other CYP3A4 substrates/inhibitors: Strong CYP3A4 inhibitors (e.g., ketoconazole, certain protease inhibitors) may increase Mirtaz plasma levels, requiring dose adjustment; strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin) may reduce efficacy.
• Warfarin: Rare reports of increased INR; monitor coagulation parameters if used together.

The most commonly reported side effects of Mirtaz include:

• Somnolence/sedation (very common, especially early in treatment)
• Increased appetite and weight gain
• Dry mouth
• Dizziness
• Constipation
• Fatigue/asthenia
• Abnormal dreams

Serious side effects requiring prompt medical attention

• Agranulocytosis/neutropenia: A rare but potentially serious drop in white blood cell count. Seek prompt medical attention for fever, sore throat, mouth ulcers, or other signs of infection while on Mirtaz, and periodic blood counts may be advised.
• Serotonin syndrome when combined with other serotonergic drugs (see Interactions).
• Orthostatic hypotension — dizziness or fainting on standing (see Precautions).
• Increased suicidal thoughts, especially in children, adolescents, and young adults (see Precautions).
• Rare mania/hypomania activation.
• Rare seizures.

Pregnancy: Mirtaz should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Available data have not established a clear pattern of major birth defects, but neonates exposed to antidepressants late in the third trimester have occasionally shown complications such as respiratory distress, feeding difficulty, or withdrawal-type symptoms requiring monitoring. Abrupt discontinuation during pregnancy is not recommended without medical advice; discuss risks and benefits with a physician.

Lactation: Mirtaz is excreted in human breast milk in small amounts. Use during breastfeeding only after consulting a physician, who can weigh the benefits of treatment against potential effects on the nursing infant, and monitor the infant for sedation or feeding difficulty if used.

Agranulocytosis

Rare but potentially serious reductions in white blood cell count have been reported with Mirtaz. Patients and caregivers should be educated to watch for and promptly report fever, sore throat, mouth sores, or other signs of infection; treatment should generally be discontinued if significant neutropenia occurs (see Side Effects).

Serotonin Syndrome

Concomitant use of Mirtaz with other serotonergic agents, or use with/soon after an MAOI, can precipitate a potentially life-threatening serotonin syndrome (see Contraindications and Interactions). Discontinue immediately and seek emergency care if symptoms such as agitation, hallucinations, rapid heart rate, fever, muscle rigidity, or coordination problems occur.

Orthostatic Hypotension

Mirtaz may cause a drop in blood pressure on standing; use with caution in patients with cardiovascular disease, cerebrovascular disease, or conditions predisposing to hypotension.

Sedation and Impaired Performance

Sedation is common, especially at the start of treatment or with dose increases. Patients should avoid driving or operating hazardous machinery until they know how Mirtaz affects them, and should avoid alcohol.

Weight Gain and Metabolic Effects

Increased appetite and weight gain are common; monitor weight, and use with caution in patients with diabetes or dyslipidemia.

Discontinuation

Do not stop Mirtaz abruptly after regular use; taper gradually under medical supervision to reduce the risk of discontinuation symptoms (e.g., dizziness, nausea, irritability, anxiety).

Hepatic and Renal Impairment

Clearance of Mirtaz is reduced in patients with hepatic or renal impairment; use with caution, at lower doses, and with closer monitoring.

Activation of Mania/Hypomania

Use with caution in patients with a history of bipolar disorder, as antidepressants may trigger a manic episode.

Overdose of Mirtaz alone typically causes disorientation, drowsiness, impaired memory, and tachycardia; it has a relatively wide margin of safety compared with older antidepressants when taken alone, but overdose combined with alcohol or other CNS-depressant drugs, or with other medications, can be more dangerous and potentially life-threatening.

If an overdose of Mirtaz is suspected, seek immediate medical attention or contact a poison control center/emergency services right away. Do not attempt to manage an overdose at home. Treatment in a medical facility is generally supportive, based on symptoms, with monitoring of vital signs and cardiac function; there is no specific antidote.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Elderly

Use with caution; clearance of Mirtaz is reduced in elderly patients, who may also be more susceptible to sedation and orthostatic hypotension. Start at a lower dose and titrate slowly.

Hepatic Impairment

Mirtaz clearance is reduced in patients with hepatic impairment; use lower doses with careful monitoring.

Renal Impairment

Mirtaz clearance is reduced in patients with moderate to severe renal impairment; use lower doses with careful monitoring.

Pediatric

Safety and efficacy of Mirtaz have not been established in patients under 18 years of age; use is not recommended in this age group outside specialist guidance (see Pediatric Uses and Precautions).

An initial therapeutic response to Mirtaz may take 1–4 weeks, with full benefit sometimes taking longer. Once a response is achieved, treatment is generally continued for at least 6 months (and often longer) to consolidate remission and reduce risk of relapse, as advised by the treating physician. Treatment should not be stopped abruptly, and the total duration should be individualized based on clinical response and history of depressive episodes.

Atypical antidepressants; Noradrenergic and Specific Serotonergic Antidepressants (NaSSAs).

Mirtazapine works primarily by antagonizing central presynaptic alpha-2 adrenergic autoreceptors and heteroreceptors, which increases the release of norepinephrine and serotonin into the synapse. It also blocks postsynaptic 5-HT2 and 5-HT3 serotonin receptors, channeling the increased serotonergic activity through 5-HT1A receptors, which is thought to underlie its antidepressant effect while minimizing nausea and sexual side effects typical of SSRIs. Its potent antagonism of H1-histamine receptors accounts for its sedative and appetite-stimulating properties.

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The safety and efficacy of Mirtaz have not been established in patients under 18 years of age, and it is not approved for use in this population. As with other antidepressants, Mirtaz carries a boxed warning for increased risk of suicidal thinking and behavior in children, adolescents, and young adults (see Precautions and Warnings). If a physician determines that treatment with Mirtaz is necessary in a minor after careful risk-benefit assessment, close clinical monitoring for worsening depression, unusual behavior changes, and suicidal ideation is essential, particularly during the first few months of therapy and after any dose adjustment.