Remeron - Drug Monograph

Introduction

Remeron (mirtazapine) is a tetracyclic antidepressant approved by the FDA in 1996. It belongs to the noradrenergic and specific serotonergic antidepressant (NaSSA) class and is primarily used for the treatment of major depressive disorder. Unlike many other antidepressants, mirtazapine has a unique pharmacological profile that contributes to both its therapeutic effects and distinctive side effect pattern.

Mechanism of Action

Mirtazapine acts as an antagonist at central presynaptic α2-adrenergic autoreceptors and heteroreceptors, which enhances noradrenergic and serotonergic neurotransmission. It is also a potent antagonist of 5-HT2 and 5-HT3 receptors, which contributes to its antidepressant and anxiolytic effects while minimizing serotonergic side effects. Additionally, it has strong histamine H1 receptor antagonism, which accounts for its sedative properties.

Indications

• FDA-approved for the treatment of major depressive disorder (MDD)
• Off-label uses include:

- Generalized anxiety disorder - Post-traumatic stress disorder - Insomnia - Appetite stimulation in cachexic patients - Prevention of chemotherapy-induced nausea and vomiting

Dosage and Administration

• Geriatric patients: Start with 7.5 mg daily
• Hepatic impairment: Use with caution, consider lower doses
• Renal impairment (CrCl <40 mL/min): Use with caution
• CYP450 poor metabolizers: May require dose reduction

Pharmacokinetics

Contraindications

• Known hypersensitivity to mirtazapine or any component of the formulation
• Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI use
• Patients with untreated narrow-angle glaucoma

Warnings and Precautions

• Boxed Warning: Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults
• Agranulocytosis/neutropenia (monitor CBC regularly)
• Serotonin syndrome risk, particularly with concomitant serotonergic drugs
• Activation of mania/hypomania in bipolar disorder
• Discontinuation syndrome (taper gradually)
• Orthostatic hypotension
• Increased appetite and weight gain
• Somnolence/sedation (caution when operating machinery)

Drug Interactions

• MAOIs: Risk of serotonin syndrome (contraindicated)
• Other serotonergic drugs (SSRIs, SNRIs, tramadol): Increased serotonin syndrome risk
• CNS depressants (alcohol, benzodiazepines): Additive sedation
• Strong CYP3A4 inhibitors (ketoconazole): May increase mirtazapine levels
• Strong CYP3A4 inducers (carbamazepine): May decrease mirtazapine levels

Adverse Effects

• Somnolence (54%)
• Increased appetite (17%)
• Weight gain (12%)
• Dry mouth (25%)
• Constipation (13%)

• Agranulocytosis
• Serotonin syndrome
• Suicidal ideation
• Seizures
• Hyponatremia
• Angle-closure glaucoma

Monitoring Parameters

• Mental status and suicidal ideation (especially during initial treatment)
• Complete blood count (at baseline and periodically)
• Weight and BMI (regularly)
• Liver function tests (periodically)
• Serum sodium (in elderly patients)
• Therapeutic response and side effects
• Signs of serotonin syndrome

Patient Education

• Take medication at bedtime due to sedative effects
• Do not abruptly discontinue medication
• Report any signs of infection (fever, sore throat)
• Be aware of potential weight gain and implement healthy lifestyle measures
• Avoid alcohol and other CNS depressants
• Rise slowly from sitting/lying position to prevent dizziness
• Report any worsening depression or suicidal thoughts immediately
• Use effective contraception as effects on fetus are not well established
• Do not crush or chew Remeron SolTab tablets

References

1. FDA Prescribing Information: Remeron (mirtazapine) Tablets 2. Stahl SM. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 4th ed. Cambridge University Press; 2013. 3. Watanabe N, Omori IM, Nakagawa A, et al. Mirtazapine versus other antidepressive agents for depression. Cochrane Database Syst Rev. 2011;(12):CD006528. 4. Anttila SA, Leinonen EV. A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev. 2001;7(3):249-264. 5. Croom KF, Perry CM, Plosker GL. Mirtazapine: a review of its use in major depression and other psychiatric disorders. CNS Drugs. 2009;23(5):427-452. 6. Fagiolini A, Comandini A, Dell'Osso MC, Kasper S. Rediscovering trazodone for the treatment of major depressive disorder. CNS Drugs. 2012;26(12):1033-1049.