Side Effects of Mirtazapine
Mirtazapine's most common side effects are sedation/somnolence (23% of patients), dry mouth (25%), increased appetite (11%), and weight gain (10%), with these effects occurring significantly more frequently than placebo. 1
Most Common Side Effects
The FDA-approved labeling and clinical guidelines identify the following most frequent adverse effects:
- Sedation/Somnolence: Occurs in approximately 23% of patients compared to 14% with placebo 2, 1
- Dry mouth: Affects approximately 25% of patients versus 16% with placebo 2, 1
- Increased appetite: Reported in about 11% of patients compared to 2% with placebo 2, 1
- Weight gain: Occurs in approximately 10% of patients versus 1% with placebo; mirtazapine causes higher weight gain than sertraline, trazodone, or venlafaxine 2, 1
- Dizziness: Commonly reported in clinical trials 1
- Constipation: A frequently reported gastrointestinal side effect 2
Serious and Potentially Life-Threatening Side Effects
Hematologic Effects
- Low white blood cell count (agranulocytosis/neutropenia): Rare but potentially serious; patients should immediately report fever, sore throat, flu-like symptoms, chills, mouth/nose sores, or infections 1, 3
Serotonin Syndrome
- Life-threatening condition when combined with other serotonergic medications; symptoms include agitation, confusion, fast heart rate, dizziness, flushing, tremors, stiff muscles, seizures, hallucinations, coma, blood pressure changes, sweating, hyperthermia, loss of coordination, nausea, vomiting, and diarrhea 1
Cardiovascular and Metabolic Effects
- Heart rhythm problems: Including QT prolongation 1
- Increased cholesterol and triglyceride levels: Elevated fat levels in blood 1
- Orthostatic hypotension: Particularly in elderly patients 2
Neuropsychiatric Effects
- Increased suicidal thoughts or actions: Particularly in patients under 24 years of age, especially within the first few months of treatment or when dose is changed 1
- Mania or hypomania: In patients with history of bipolar disorder; symptoms include greatly increased energy, racing thoughts, unusually grand ideas, talking more/faster than usual, severe trouble sleeping, reckless behavior, excessive happiness or irritability 1
- Seizures (convulsions): Reported in clinical trials 1
Other Serious Effects
- Angle-closure glaucoma: May cause eye pain, vision changes, or swelling/redness in or around the eye 1
- Severe skin reaction: May include rash, fever, swollen glands, and organ involvement (liver, kidney, lung, heart); reaction may sometimes be fatal 1
- Hyponatremia (low sodium levels): Can be serious and potentially fatal, especially in elderly patients; symptoms include headache, memory changes, weakness, unsteadiness leading to falls, difficulty concentrating, confusion; severe cases may cause hallucinations, seizures, respiratory arrest, fainting, coma, or death 1
- Changes in liver function tests: Elevated alanine aminotransferase levels have been reported 3
Discontinuation Syndrome
Suddenly stopping mirtazapine may cause serious withdrawal symptoms including: 1
- Dizziness, irritability, agitation, anxiety
- Sweating, seizures, tinnitus (ringing in ears)
- Nausea, vomiting, sleep problems
- Tiredness, confusion, electric shock sensations (paresthesia)
- Tremor, headache, abnormal dreams
- Mood changes, hypomania
Healthcare providers should decrease the dose slowly rather than abruptly discontinuing the medication. 1
Special Population Considerations
- Elderly patients: More susceptible to sedation, orthostatic hypotension, and hyponatremia 2
- Patients with cardiovascular disease: Mirtazapine has been shown to be safe in this population 2
- Hepatic or renal impairment: Clearance may be reduced, requiring careful dosage titration 4
Advantageous Side Effect Profile Compared to Other Antidepressants
Mirtazapine has fewer anticholinergic, adrenergic, and serotonergic adverse effects compared to tricyclic antidepressants: 5, 3, 4
- Minimal cardiovascular and anticholinergic effects 6
- Essentially lacks gastrointestinal symptoms, insomnia, and sexual dysfunction common with SSRIs 6, 4
- Fewer anticholinergic effects (dry mouth, constipation, abnormal accommodation/vision), cardiac effects (palpitations, tachycardia), and neurological effects (tremor, vertigo) compared to amitriptyline 3
Clinical Context for Side Effects
The sedative and appetite-stimulating effects can be therapeutically beneficial in specific clinical situations: 5, 2