“If this blog helped you out, don’t keep it to yourself—share the link on your socials!” 👍 “Like what you read? Spread the love and share this blog on your social media.” 👍 “Found this useful? Hit share and let your friends know too!” 👍 “If you enjoyed this post, please share the URL with your friends online.” 👍 “Sharing is caring—drop this link on your social media if it helped you.”

Monday, July 28, 2025

Mirtazapine


Generic Name: Mirtazapine
Brand Names: Remeron, Remeron SolTab
Drug Class: Tetracyclic antidepressant
Pharmacologic Class: Noradrenergic and specific serotonergic antidepressant (NaSSA)
Legal Status: Prescription-only (Rx)

Mechanism of Action

Mirtazapine is an atypical antidepressant that exerts its effect through multiple central nervous system pathways. It functions primarily as:

  • A potent presynaptic alpha-2 adrenergic autoreceptor antagonist, which enhances the release of norepinephrine and serotonin (5-HT)

  • A selective serotonin 5-HT2 and 5-HT3 receptor antagonist, increasing postsynaptic 5-HT1A transmission

  • A strong histamine H1 receptor inverse agonist, contributing to its pronounced sedative effects

  • A weak antagonist of muscarinic cholinergic and peripheral alpha-1 adrenergic receptors

The combination of noradrenergic enhancement and serotonergic modulation underlies its antidepressant efficacy. Blocking 5-HT2 and 5-HT3 also helps minimize side effects like insomnia, anxiety, nausea, and sexual dysfunction, which are common with SSRIs.

Therapeutic Indications

Approved Use:

  • Major Depressive Disorder (MDD) in adults

Common Off-Label Uses:

  • Generalized Anxiety Disorder (GAD)

  • Post-Traumatic Stress Disorder (PTSD)

  • Social Anxiety Disorder

  • Insomnia (especially associated with depression)

  • Appetite stimulation in underweight patients or those with cachexia

  • Chemotherapy-induced nausea and vomiting (supportive care)

  • Pruritus (chronic, idiopathic, or renal-related)

Dosage and Administration

Formulations:

  • Tablets: 15 mg, 30 mg, 45 mg

  • Orally disintegrating tablets (ODT): 15 mg, 30 mg, 45 mg

Initial Dose:

  • 15 mg once daily at bedtime (due to sedation)

Maintenance Dose:

  • Typical therapeutic range: 15–45 mg/day

  • Titration in 15 mg increments every 1–2 weeks based on clinical response

Administration Notes:

  • Can be taken with or without food

  • Discontinuation should be gradual to avoid withdrawal symptoms

  • Not typically combined with other antidepressants unless under specialist supervision

Pharmacokinetics

  • Bioavailability: Approximately 50%

  • Peak Plasma Concentration: Reached in ~2 hours

  • Protein Binding: Approximately 85%

  • Metabolism: Extensive hepatic metabolism primarily via CYP1A2, CYP2D6, and CYP3A4

  • Half-Life: 20–40 hours (once-daily dosing appropriate)

  • Excretion: Mainly via urine (~75%), rest via feces

Contraindications

  • Known hypersensitivity to mirtazapine or any component of the formulation

  • Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping MAOIs

  • Use in combination with other serotonergic drugs without appropriate monitoring

  • Severe hepatic impairment (relative contraindication; requires dose adjustment)

Warnings and Precautions

  • Suicidality Risk: Increased risk of suicidal thoughts and behaviors in young adults, adolescents, and children; regular monitoring recommended especially at therapy initiation and during dose changes

  • Hematologic Effects: Rare cases of agranulocytosis, neutropenia; monitor CBC in patients presenting with sore throat, fever, or other infection signs

  • Mania/Hypomania: Use cautiously in patients with bipolar disorder; antidepressants may induce manic episodes

  • QT Prolongation: May increase QT interval; avoid in patients with known QT prolongation, recent MI, or electrolyte imbalance

  • Hyponatremia/SIADH: Syndrome of inappropriate antidiuretic hormone secretion may occur, especially in elderly

  • Withdrawal Symptoms: Abrupt discontinuation can cause dizziness, agitation, sleep disturbances, and flu-like symptoms

  • Seizure Risk: Although rare, seizures may occur; use with caution in patients with seizure history

Adverse Effects

Very Common (≥10%):

  • Somnolence

  • Increased appetite

  • Weight gain

  • Dry mouth

Common (1–10%):

  • Dizziness

  • Constipation

  • Abnormal dreams

  • Elevated cholesterol or triglycerides

  • Peripheral edema

Less Common (<1%):

  • Hepatic enzyme elevation

  • Rash

  • Tremor

  • Anxiety

  • Akathisia

Rare but Serious:

  • Agranulocytosis

  • Serotonin syndrome (when combined with serotonergic agents)

  • SIADH and hyponatremia

  • QT prolongation

  • Suicidal ideation

Special Populations

Elderly:

  • Start at lower doses (7.5–15 mg); monitor for excessive sedation and falls

Hepatic Impairment:

  • Clearance may be reduced; dose adjustment required

Renal Impairment:

  • Use with caution; metabolites excreted renally

Pregnancy:

  • Use only if potential benefits justify the potential risk

  • Not associated with major malformations but insufficient data for safety

Lactation:

  • Excreted into breast milk; caution advised, consider alternatives if breastfeeding

Drug Interactions

  • MAOIs: Contraindicated due to risk of hypertensive crisis or serotonin syndrome

  • SSRIs/SNRIs/Tryptans/Tramadol: Additive serotonergic effect increases serotonin syndrome risk

  • CYP450 inducers/inhibitors:

    • CYP3A4 inhibitors (ketoconazole, erythromycin): May increase mirtazapine levels

    • CYP3A4 inducers (carbamazepine, phenytoin): May reduce mirtazapine plasma concentration

  • Alcohol and CNS depressants: Potentiation of sedative effects

  • Benzodiazepines or antipsychotics: Additive CNS depression and risk of hypotension

Monitoring Parameters

  • Clinical response to depressive symptoms (especially in the first 4–6 weeks)

  • Suicidal thoughts and behavior (particularly in younger adults and adolescents)

  • Weight, BMI, and metabolic profile (lipids, glucose)

  • Complete blood count if signs of infection occur

  • ECG if patient has cardiac risk factors or is on other QT-prolonging agents

  • Signs of serotonin syndrome if coadministered with other serotonergic agents

Comparison with Other Antidepressants

Mirtazapine vs SSRIs (e.g., sertraline, fluoxetine):

  • Lower incidence of sexual dysfunction

  • More sedating and appetite-stimulating

  • Faster onset of sleep benefits

Mirtazapine vs SNRIs (e.g., venlafaxine):

  • Less risk of nausea and vomiting

  • Lower risk of dose-dependent hypertension

  • More suitable for anxious or underweight patients

Mirtazapine vs Trazodone:

  • Similar sedative benefits

  • Mirtazapine more effective for depression

  • Trazodone more frequently used for pure insomnia

Overdose

Symptoms:

  • Somnolence

  • Disorientation

  • Tachycardia

  • Agitation

  • Rarely seizures, cardiac toxicity, or fatality

Management:

  • Supportive care

  • Monitor cardiac rhythm and vital signs

  • Gastric lavage if within 1 hour of ingestion

  • No specific antidote; dialysis ineffective

Storage and Handling

  • Store at 20–25°C

  • Protect from moisture and direct sunlight

  • Keep tablets in original packaging

  • Keep out of reach of children




on
Labels:

No comments:

Post a Comment

Subscribe to: Post Comments (Atom)