Mirtazapine (Remeron)

Class

Noradrenergic and specific serotonergic antidepressant (NaSSA)

Mechanism

Antagonist at central presynaptic alpha-2-adrenergic autoreceptors and heteroreceptors, enhancing norepinephrine and serotonin release; antagonizes 5-HT2 and 5-HT3 receptors and potent H1 histamine receptor antagonist contributing to sedation.

FDA-Approved Use

Major depressive disorder (MDD)

Off-Label Use

Generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), panic disorder, insomnia, chronic tension headache prophylaxis, post-stroke depression (PSD), depression in dementia

Formulation

Oral tablets (7.5 mg, 15 mg, 30 mg, 45 mg)

Titration

7.5–15 mg p.o. nightly, titrating as clinically appropriate

Dose Range

15–45 mg/day

Kinetics

Half-life ~20–40 hours; metabolized via CYP1A2, CYP2D6, and CYP3A4; steady state in ~1 week

Common AEs

Sedation, increased appetite, weight gain, dry mouth, dizziness, constipation, elevated cholesterol and triglycerides

Serious/Rare AEs

Agranulocytosis (rare), serotonin syndrome

Monitoring

Monitor weight, metabolic parameters (lipids, glucose), sedation level, and mood symptoms

Black Box Warning

Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults with MDD and other psychiatric disorders

Considerations

Mirtazapine should be used cautiously in elderly patients due to increased risks of sedation, falls, and weight gain. Limited evidence supports its use in neurodegenerative disorders such as Parkinson’s disease (PD) or dementia, though it may help with insomnia and weight loss in some patients. Regular monitoring for metabolic effects is recommended in patients with metabolic risk factors.