What are the contraindications to starting mirtazapine (Remeron)?

Contraindications to Starting Mirtazapine

Mirtazapine is absolutely contraindicated in patients currently taking or who have taken MAOIs within the past 14 days, those with known hypersensitivity to mirtazapine, and should be avoided in patients with active psychotic disorders. 1

Absolute Contraindications

MAOI Use

• Concurrent use or use within 14 days of stopping MAOIs (including linezolid and intravenous methylene blue) is contraindicated due to increased risk of serotonin syndrome 1
• This includes both traditional MAOIs (phenelzine, tranylcypromine, selegiline, isocarboxazid) and the MAOIs linezolid and IV methylene blue 1

Hypersensitivity

• Known hypersensitivity to mirtazapine or any excipients is an absolute contraindication 1
• Severe skin reactions have been reported, including DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms), Stevens-Johnson syndrome, bullous dermatitis, erythema multiforme, and toxic epidermal necrolysis 1

Active Psychotic Disorders

• Mirtazapine should not be administered to patients with active psychotic disorders 2

Relative Contraindications and Major Precautions

Cardiovascular Concerns

• Exercise caution in patients with known cardiovascular disease or family history of QT prolongation, as mirtazapine can prolong the QTc interval and has been associated with Torsades de Pointes, ventricular tachycardia, and sudden death in postmarketing reports 1
• While mirtazapine has been shown to be safe in cardiovascular disease patients and has minimal cardiovascular effects compared to tricyclic antidepressants, monitoring is warranted 2, 3

Angle-Closure Glaucoma Risk

• Patients with anatomically narrow angles who do not have a patent iridectomy are at risk for angle-closure attacks, as pupillary dilation can occur with mirtazapine use 1

Hematologic Monitoring Required

• While not an absolute contraindication, be aware that agranulocytosis and severe neutropenia have occurred (approximately 1 in 1,000 patients) 1, 4
• If patients develop sore throat, fever, stomatitis, or other signs of infection with low WBC count, mirtazapine should be discontinued immediately 1

Hepatic and Renal Impairment

• Careful dosage titration and close monitoring are recommended in patients with hepatic or renal insufficiency, though these are not absolute contraindications 3

Drug Interactions Requiring Avoidance

• Avoid concomitant use with other serotonergic drugs unless clinically essential, due to increased serotonin syndrome risk (SSRIs, SNRIs, triptans, tricyclics, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, St. John's Wort) 1
• Avoid concomitant use with benzodiazepines and alcohol, as mirtazapine increases impairment of cognitive and motor skills 1, 3
• Avoid concomitant use with other QTc-prolonging medications in patients with cardiovascular risk factors 1

Special Populations

• Pregnancy and lactation: While the evidence provided focuses on obesity medications, standard practice dictates careful risk-benefit assessment in pregnancy and lactation for all antidepressants 2

Clinical Pearls

Common pitfall: Failing to recognize that linezolid and IV methylene blue are MAOIs—these require the same 14-day washout period as traditional MAOIs 1

Monitoring strategy: Baseline assessment should include cardiovascular history, family history of QT prolongation, current medication review for drug interactions, and consideration of baseline CBC given agranulocytosis risk 1, 3