Mirtazapine Side Effects
Mirtazapine causes sedation, increased appetite, and weight gain as its most common side effects, occurring in approximately 23%, 11%, and 10% of patients respectively, with serious but rare risks including agranulocytosis, serotonin syndrome, and severe skin reactions. 1, 2
Most Common Side Effects
The four most frequently reported side effects are: 2
- Sleepiness/Somnolence: Occurs in approximately 23% of patients (versus 14% with placebo), making it the most common side effect 1
- Increased appetite: Affects about 11% of patients (versus 2% with placebo) 1
- Weight gain: Reported in approximately 10% of patients (versus 1% with placebo); mirtazapine causes more weight gain than sertraline, trazodone, or venlafaxine 1
- Dry mouth: Occurs in approximately 25% of patients (versus 16% with placebo) 1
- Dizziness: Commonly reported alongside the above effects 2
Serious Side Effects Requiring Immediate Medical Attention
Hematologic Effects
- Agranulocytosis/Low white blood cell count: Rare but potentially life-threatening (approximately 1 in 1,000 patients), though usually reversible when medication is stopped 2, 3
- Warning signs include: fever, sore throat, flu-like symptoms, chills, mouth and nose sores, or infections 2
Serotonin Syndrome
- Potentially life-threatening when mirtazapine is combined with MAOIs, linezolid, or intravenous methylene blue 2
- Symptoms requiring emergency care: agitation, confusion, fast heartbeat, dizziness, flushing, tremors, stiff muscles, seizures, hallucinations, coma, blood pressure changes, sweating, hyperthermia, loss of coordination, nausea, vomiting, diarrhea 2
Other Serious Reactions
- Severe skin reactions: May include rash, fever, swollen glands, and organ involvement (liver, kidney, lung, heart); can be fatal 2
- Angle-closure glaucoma: Eye pain, vision changes, swelling or redness around the eye 2
- Heart rhythm problems: Including QT prolongation 2
- Seizures: Particularly in susceptible individuals 2
Metabolic and Cardiovascular Effects
- Increased cholesterol and triglycerides: Elevated lipid levels occur with mirtazapine use 2
- Hyponatremia (low sodium): Can be serious or fatal, especially in elderly patients 2
- Mild symptoms: headache, memory changes, weakness, unsteadiness, difficulty concentrating, confusion
- Severe symptoms: hallucinations, seizures, respiratory arrest, fainting, coma, death
- Liver function changes: Elevated liver enzymes may occur 2
Psychiatric Side Effects
- Mania/hypomania: Particularly in patients with bipolar disorder history 2
- Symptoms include: greatly increased energy, racing thoughts, grandiose ideas, rapid speech, severe insomnia, reckless behavior, excessive happiness or irritability
- Increased suicidal thoughts: Especially in patients under 24 years of age, particularly in the first few months of treatment or with dose changes 2
Discontinuation Syndrome
Abrupt cessation can cause serious withdrawal symptoms; dose should be tapered slowly 2
Symptoms include: 2
- Dizziness, irritability, agitation, anxiety, sweating
- Seizures, tinnitus, nausea, vomiting
- Sleep problems, tiredness, confusion
- Electric shock sensations (paresthesia), tremor, headache
- Abnormal dreams, mood changes, hypomania
Advantageous Side Effect Profile
Mirtazapine notably lacks many side effects common to other antidepressants: 1, 4
- Minimal anticholinergic effects: Unlike tricyclic antidepressants 1, 4
- Minimal cardiovascular effects: Safe in patients with cardiovascular disease 1, 4
- Essentially no gastrointestinal symptoms: Unlike SSRIs 1, 4
- No sexual dysfunction: Unlike SSRIs, making it useful for patients experiencing sexual side effects from other antidepressants 1, 3
- No insomnia: In fact, improves sleep when taken at bedtime 1, 4
Special Population Considerations
- Elderly patients: More susceptible to sedation, orthostatic hypotension, and hyponatremia 1
- Hepatic or renal impairment: Clearance may be reduced, requiring careful dose titration 5
- Pregnancy: Unknown safety; registry available at 1-844-405-6185 2
- Breastfeeding: Mirtazapine passes into breast milk 2
Clinical Context for Side Effects
The sedative and appetite-stimulating effects can be therapeutically beneficial in specific situations: 1
- Sedation helps patients with comorbid insomnia when dosed at bedtime 1
- Weight gain is advantageous in patients with anorexia, weight loss, or elderly patients with dementia and depression 1
- However, weight gain should be avoided in patients with obesity, cardiovascular disease, or metabolic syndrome 6