No

Antidepressant, Alpha-2 Antagonist

Treatment of depression

C

Hypersensitivity to mirtazapine; use of monoamine oxidase inhibitors within 14 days

Discontinue immediately if signs and symptoms of neutropenia/agranulocytosis occur. May cause sedation, resulting in impaired performance of tasks requiring alertness (ie, operating machinery or driving). Sedative effects may be additive with other CNS depressants and/or ethanol. The degree of sedation is moderate-high relative to other antidepressants. May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disease. The risks of orthostatic hypotension or anticholinergic effects are low relative to other antidepressants. The incidence of sexual dysfunction with mirtazapine is generally lower than with SSRIs.

>10%:

Central nervous system: Somnolence

Endocrine & metabolic: Increased cholesterol

Gastrointestinal: Constipation, xerostomia, increased appetite, weight gain

1% to 10%:

Cardiovascular: Hypertension, vasodilatation, peripheral edema, edema

Central nervous system: Dizziness, abnormal dreams, abnormal thoughts, confusion, malaise

Endocrine & metabolic: Increased triglycerides

Gastrointestinal: Vomiting, anorexia

Genitourinary: Urinary frequency

Neuromuscular & skeletal: Myalgia, back pain, arthralgias, tremor, weakness

Respiratory: Dyspnea

Miscellaneous: Flu-like symptoms, thirst

<1%: Orthostatic hypotension, seizures (1 case reported), dehydration, weight loss, agranulocytosis, neutropenia, lymphadenopathy, liver function test increases

CYP1A2, 2C9, 2D6, and 3A3/4 enzyme substrate

Possibly serious or fatal reactions can occur when given with or when given within 14 days of a monoamine oxidase inhibitor

Mirtazapine is a tetracyclic antidepressant that works by its central presynaptic alpha₂-adrenergic antagonist effects, which results in increased release of norepinephrine and serotonin. It is also a potent antagonist of 5HT2 and 5HT3 serotonin receptors and H1 histamine receptors and a moderate peripheral alpha₁-adrenergic and muscarinic antagonist; it does not inhibit the reuptake of norepinephrine or serotonin.

Onset of effect: Therapeutic effects generally in >2 weeks

Protein binding: 85%

Metabolism: Extensive by cytochrome P-450 enzymes in the liver

Bioavailability: 50%

Half-life: 20-40 hours

Time to peak serum concentration: 2 hours

Elimination: Extensive hepatic metabolism via demethylation and hydroxylation, metabolites eliminated primarily renally (75%) and some via the feces (15%); elimination is hampered with renal dysfunction or hepatic dysfunction.

Adults: Oral: Initial: 15 mg nightly, titrate up to 15-45 mg/day with dose increases made no more frequently than every 1-2 weeks; there is an inverse relationship between dose and sedation

Alcohol: Additive CNS effect, avoid use

Patients should be monitored for signs of agranulocytosis or severe neutropenia such as sore throat, stomatitis or other signs of infection or a low WBC; monitor for improvement in clinical signs and symptoms of depression, improvement may be observed within 1-4 weeks after initiating therapy

No information available to require special precautions

Significant xerostomia occurs in up to 25% of patients

Take exactly as directed (do not increase dose or frequency); may take 2-3 weeks to achieve desired results. Take once-a-day dose at bedtime. Avoid excessive alcohol, caffeine, and other prescription or OTC medications not approved by prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience drowsiness, dizziness, or lightheadedness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea, vomiting, anorexia, or dry mouth (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); or orthostatic hypotension (use caution when climbing stairs or changing position from lying or sitting to standing). Report persistent insomnia, agitation, or confusion; muscle cramping, tremors, weakness, or change in gait; breathlessness or difficulty breathing; chest pain, palpitations, or rapid heartbeat; change in urinary pattern; vision changes or eye pain; yellowing of eyes or skin; pale stools/dark urine; or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Tablet: 15 mg, 30 mg

"Mirtazapine - A New Antidepressant," Med Lett Drugs Ther, 1996, 38(990):113-4.

Stimmel GL, Dopheide JA, and Stahl SM, "Mirtazapine: An Antidepressant With Noradrenergic and Specific Serotonergic Effects," Pharmacotherapy, 1997, 17(1):10-21.