Mirtazapine

Last updated on RxList: 10/30/2020
Mirtazapine Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Mirtazapine?

Mirtazapine is a tetracyclic antidepressant used to treat major depressive disorder.

What Are Side Effects of Mirtazapine?

Side effects of mirtazapine include:

Dosage for Mirtazapine

The recommended starting dose for mirtazapine is 15 mg/day, administered in a single dose, preferably in the evening prior to sleep. In the controlled clinical trials establishing the efficacy of mirtazapine in the treatment of major depressive disorder, the effective dose range was generally 15 to 45 mg/day.

Mirtazapine In Children

Safety and effectiveness of mirtazapine in the pediatric population have not been established.

What Drugs, Substances, or Supplements Interact with Mirtazapine?

Mirtazapine may interact with other medicines such as:

  • monoamine oxidase inhibitors (MAOIs),
  • serotonergic drugs,
  • drugs affecting hepatic metabolism,
  • CYP enzyme inducers (such as phenytoin, carbamazepine, rifampicin),
  • CYP enzyme inhibitors (such as cimetidine, ketoconazole),
  • HIV protease inhibitors,
  • azole antifungals,
  • erythromycin,
  • nefazodone,
  • paroxetine,
  • amitriptyline,
  • warfarin,
  • lithium,
  • risperidone,
  • alcohol,
  • diazepam, and
  • QTc-prolonging drugs (such as some antipsychotics and antibiotics)

Tell your doctor all medications and supplements you use.

Mirtazapine During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using mirtazapine; it is unknown how it would affect a fetus. Because some mirtazapine may be excreted into breast milk, caution should be exercised when mirtazapine is administered to nursing women. Consult your doctor before breastfeeding.

Additional Information

Our Mirtazapine Tablet Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

QUESTION

Depression is a(n) __________ . See Answer
Mirtazapine Consumer Information

Get emergency medical help if you have signs of an allergic reaction (hives, joint pain, fever, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have:

  • racing thoughts, decreased need for sleep, unusual risk-taking behavior, feelings of extreme happiness or sadness, being more talkative than usual;
  • blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • a light-headed feeling, like you might pass out;
  • severe rash, blisters, or swelling on the palms of your hands or the soles of your feet;
  • a seizure;
  • low white blood cell counts--fever, chills, sore throat, cough, sores in your mouth or nose, flu-like symptoms, trouble breathing; or
  • low sodium level --headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady.

Seek medical attention right away if you have symptoms of serotonin syndrome, such as: agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea.

Common side effects include:

  • drowsiness, dizziness;
  • increased appetite; or
  • weight gain.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Mirtazapine (Mirtazapine)

SLIDESHOW

Learn to Spot Depression: Symptoms, Warning Signs, Medication See Slideshow
Mirtazapine Professional Information

SIDE EFFECTS

Associated With Discontinuation Of Treatment

Approximately 16% of the 453 patients who received Mirtazapine tablets, USP in US 6-week controlled clinical trials discontinued treatment due to an adverse experience, compared to 7% of the 361 placebo-treated patients in those studies. The most common events (≥1%) associated with discontinuation and considered to be drug related (i.e., those events associated with dropout at a rate at least twice that of placebo) are included in Table 2.

Table 2: Common Adverse Events Associated with Discontinuation of Treatment in 6-Week US Mirtazapine Trials

Adverse EventPercentage of Patients Discontinuing with Adverse Event
Mirtazapine (n=453)Placebo (n=361)
Somnolence10.4%2.2%
Nausea1.5%0%

Commonly Observed Adverse Events In US Controlled Clinical Trials

The most commonly observed adverse events associated with the use of Mirtazapine tablets, USP (incidence of 5% or greater) and not observed at an equivalent incidence among placebo-treated patients (mirtazapine incidence at least twice that for placebo) are listed in Table 3.

Table 3: Common Treatment-Emergent Adverse Events Associated With the Use of Mirtazapine in 6–Week US Trials

Adverse EventPercentage of Patients Reporting Adverse Event
Mirtazapine (n=453)Placebo (n=361)
Somnolence54%18%
Increased Appetite17%2%
Weight Gain12%2%
Dizziness7%3%

Adverse Events Occurring At An Incidence Of 1% Or More Among Mirtazapine-Treated Patients

Table 4 enumerates adverse events that occurred at an incidence of 1% or more, and were more frequent than in the placebo group, among Mirtazapine tablets, USP-treated patients who participated in short-term US placebocontrolled trials in which patients were dosed in a range of 5 to 60 mg/day. This table shows the percentage of patients in each group who had at least 1 episode of an event at some time during their treatment. Reported adverse events were classified using a standard COSTART-based dictionary terminology.

The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other investigations involving different treatments, uses, and investigators.

The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side-effect incidence rate in the population studied.

Table 4: Incidence of Adverse Clinical Experiences (≥1%) in Short-Term US Controlled Studies

Body System
Adverse Clinical Experience
MIRTAZAPINE (n=453)Placebo (n=361)
Body as a Whole
Asthenia8%5%
Flu Syndrome5%3%
Back Pain2%1%
Digestive System
Dry Mouth25%15%
Increased Appetite17%2%
Constipation13%7%
Metabolic and Nutritional Disorders
Weight Gain12%2%
Peripheral Edema2%1%
Edema1%0%
Musculoskeletal System
Myalgia2%1%
Nervous System
Somnolence54%18%
Dizziness7%3%
AbnormalDreams4%1%
Thinking Abnormal3%1%
Tremor2%1%
Confusion2%0%
Respiratory System
Dyspnea1%0%
Urogenital System
Urinary Frequency2%1%
*Events reported by at least 1% of patients treated with mirtazapine are included, except the following events, which had an incidence on placebo greater than or equal to mirtazapine: headache, infection, pain, chest pain, palpitation, tachycardia, postural hypotension, nausea, dyspepsia, diarrhea, flatulence, insomnia, nervousness, libido decreased, hypertonia, pharyngitis, rhinitis, sweating, amblyopia, tinnitus, taste perversion.

ECG Changes

The electrocardiograms for 338 patients who received Mirtazapine tablets, USP and 261 patients who received placebo in 6-week, placebo-controlled trials were analyzed. Prolongation in QTc ≥ 500 msec was not observed among mirtazapine-treated patients; mean change in QTc was +1.6 msec for mirtazapine and -3.1 msec for placebo. Mirtazapine was associated with a mean increase in heart rate of 3.4 bpm, compared to 0.8 bpm for placebo. The clinical significance of these changes is unknown.

The effect of mirtazapine on QTc interval was assessed in a clinical randomized trial with placebo and positive (moxifloxacin) controls involving 54 healthy volunteers using exposure response analysis. This trial showed a positive relationship between mirtazapine concentrations and prolongation of the QTc interval. However, the degree of QT prolongation observed with both 45 mg (therapeutic) and 75 mg (supratherapeutic) doses of mirtazapine was not at a level generally considered to be clinically meaningful.

Other Adverse Events Observed During The Premarketing Evaluation Of Mirtazapine

During its premarketing assessment, multiple doses of Mirtazapine tablets, USP were administered to 2796 patients in clinical studies. The conditions and duration of exposure to mirtazapine varied greatly, and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient and outpatient studies, fixed-dose and titration studies. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of untoward events into a smaller number of standardized event categories.

In the tabulations that follow, reported adverse events were classified using a standard COSTART-based dictionary terminology. The frequencies presented, therefore, represent the proportion of the 2796 patients exposed to multiple doses of mirtazapine who experienced an event of the type cited on at least 1 occasion while receiving mirtazapine. All reported events are included except those already listed in Table 4, those adverse experiences subsumed under COSTART terms that are either overly general or excessively specific so as to be uninformative, and those events for which a drug cause was very remote.

It is important to emphasize that, although the events reported occurred during treatment with mirtazapine, they were not necessarily caused by it.

Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on 1 or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients. Only those events not already listed in Table 4 appear in this listing.

Events of major clinical importance are also described in the WARNINGS and PRECAUTIONS sections.

Body as a Whole: frequent: malaise, abdominal pain, abdominal syndrome acute; infrequent: chills, fever, face edema, ulcer, photosensitivity reaction, neck rigidity, neck pain, abdomen enlarged; rare: cellulitis, chest pain substernal.

Cardiovascular System: frequent: hypertension, vasodilatation; infrequent: angina pectoris, myocardial infarction, bradycardia, ventricular extrasystoles, syncope, migraine, hypotension; rare: atrial arrhythmia, bigeminy, vascular headache, pulmonary embolus, cerebral ischemia, cardiomegaly, phlebitis, left heart failure.

Digestive System: frequent: vomiting, anorexia; infrequent: eructation, glossitis, cholecystitis, nausea and vomiting, gum hemorrhage, stomatitis, colitis, liver function tests abnormal; rare: tongue discoloration, ulcerative stomatitis, salivary gland enlargement, increased salivation, intestinal obstruction, pancreatitis, aphthous stomatitis, cirrhosis of liver, gastritis, gastroenteritis, oral moniliasis, tongue edema.

Endocrine System: rare: goiter, hypothyroidism.

Hemic and Lymphatic System: rare: lymphadenopathy, leukopenia, petechia, anemia, thrombocytopenia, lymphocytosis, pancytopenia.

Metabolic and Nutritional Disorders: frequent: thirst; infrequent: dehydration, weight loss; rare: gout, SGOT increased, healing abnormal, acid phosphatase increased, SGPT increased, diabetes mellitus, hyponatremia.

Musculoskeletal System: frequent: myasthenia, arthralgia; infrequent: arthritis, tenosynovitis; rare: pathologic fracture, osteoporosis fracture, bone pain, myositis, tendon rupture, arthrosis, bursitis.

Nervous System: frequent: hypesthesia, apathy, depression, hypokinesia, vertigo, twitching, agitation, anxiety, amnesia, hyperkinesia, paresthesia; infrequent: ataxia, delirium, delusions, depersonalization, dyskinesia, extrapyramidal syndrome, libido increased, coordination abnormal, dysarthria, hallucinations, manic reaction, neurosis, dystonia, hostility, reflexes increased, emotional lability, euphoria, paranoid reaction; rare: aphasia, nystagmus, akathisia (psychomotor restlessness), stupor, dementia, diplopia, drug dependence, paralysis, grand mal convulsion, hypotonia, myoclonus, psychotic depression, withdrawal syndrome, serotonin syndrome.

Respiratory System: frequent: cough increased, sinusitis; infrequent: epistaxis, bronchitis, asthma, pneumonia; rare: asphyxia, laryngitis, pneumothorax, hiccup.

Skin and Appendages: frequent: pruritus, rash; infrequent: acne, exfoliative dermatitis, dry skin, herpes simplex, alopecia; rare: urticaria, herpes zoster, skin hypertrophy, seborrhea, skin ulcer.

Special Senses: infrequent: eye pain, abnormality of accommodation, conjunctivitis, deafness, keratoconjunctivitis, lacrimation disorder, angle-closure glaucoma, hyperacusis, ear pain; rare: blepharitis, partial transitory deafness, otitis media, taste loss, parosmia.

Urogenital System: frequent: urinary tract infection; infrequent: kidney calculus, cystitis, dysuria, urinary incontinence, urinary retention, vaginitis, hematuria, breast pain, amenorrhea, dysmenorrhea, leukorrhea, impotence; rare: polyuria, urethritis, metrorrhagia, menorrhagia, abnormal ejaculation, breast engorgement, breast enlargement, urinary urgency.

Other Adverse Events Observed During Postmarketing Evaluation Of Mirtazapine

Adverse events reported since market introduction, which were temporally (but not necessarily causally) related to mirtazapine therapy, include cases of the ventricular arrhythmia Torsades de Pointes. In the majority of these cases, however, concomitant drugs were implicated.

Cases of severe skin reactions, including Stevens-Johnson syndrome, bullous dermatitis, erythema multiforme and toxic epidermal necrolysis have also been reported.

Increased creatine kinase blood levels and rhabdomyolysis have also been reported. Hyperprolactinemia (and related symptoms, e.g., galactorrhea and gynecomastia) has been reported. Somnambulism (ambulation and other complex behaviors out of bed) has been reported.

Read the entire FDA prescribing information for Mirtazapine (Mirtazapine)

© Mirtazapine Patient Information is supplied by Cerner Multum, Inc. and Mirtazapine Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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