Mirtazapine side effects

List of side effects
Associated with discontinuation of treatment Common in U.S. clinical trials Occurrence in ≥ 1% of patients ECG changes Adverse events observed during the pre-marketing evaluation Adverse events observed during the post-marketing evaluation

Associated with discontinuation of treatment
Approximately 16 percent of the 453 patients who received Mirtazapine in U.S. 6-week controlled clinical trials discontinued treatment due to an adverse experience, compared to 7 percent 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) included somnolence and nausea. Return to top

Common in U.S. clinical trials
The most commonly observed adverse events associated with the use of Mirtazapine (incidence of 5% or greater) and not observed at an equivalent incidence among placebo-treated patients (Mirtazapine incidence at least twice that for placebo) were: somnolence, increased appetite, weight gain, dizziness. Return to top

Occurrence in ≥ 1% of patients
The list that follows enumerates adverse events that occurred at an incidence of 1% or more, and were more frequent than in the placebo group, among Mirtazapine-treated patients who participated in short-term U.S. placebo-controlled trials in which patients were dosed in a range of 5 mg/day to 60 mg/day: Return to top
 * Body as a whole: asthenia, flu syndrome, back pain.
 * Digestive system: dry mouth, increased appetite, constipation.
 * Metabolic/nutritional disorders: weight gain, peripehral edema, edema.
 * Musculoskeletal system: myaligia.
 * Nervous system: somnolence, dizziness, abnormal dreams, thinking abnormal, tremor, confusion.
 * Respiratory system: dyspnea.
 * Urogenital system: urinary frequency.

ECG changes
The electrocardiograms for 338 patients who received Mirtazapine 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 + 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. Return to top

Adverse events observed during the pre-marketing evaluation
During its premarketing assessment, multiple doses of Mirtazapine were administered to 2,796 patients in clinical studies. The conditions and duration of exposure to Mirtazapine varied greatly, and included (in overlapping categories) open and doubleblind 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 2,796 patients exposed to multiple doses of Mirtazapine who experienced an event of the type cited on at least one occasion while receiving Mirtazapine. All reported events are included except those already listed in the previous table, 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 one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1,000 patients; rare events are those occurring in fewer than 1/1,000 patients. Only those events not already listed in the previous table appear in this listing: Body as a whole Cardiovascular system Digestive system Endocrine system Hemic/lymphatic system Metabolic/nutritional disorders Musculoskeletal system Nervous system Skin/appendages Special senses Urogenital senses Return to top
 * 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.
 * 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.
 * 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.
 * rare: goiter, hypothyroidism.
 * rare: Iymphadenopathy, leukopenia, petechia, anemia, thrombocytopenia, Iymphocytosis, pancytopenia.
 * frequent: thirst
 * infrequent: dehydration, weight loss
 * rare: gout, SGOT increased, healing abnormal, acid phosphatase increased, SGPT increased, diabetes mellitus.
 * frequent: myasthenia, arthralgia
 * infrequent: arthritis, tenosynovitis
 * rare: pathologic fracture, osteoporosis fracture, bone pain, myositis, tendon rupture, arthosis, bursitis.
 * 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, stupor, dementia, diplopia, drug dependence, paralysis, grand mal convulsion, hypotonia, myoclonus, psychotic depression, withdrawal syndrome.
 * Respiratory System:frequent: cough increased, sinusitis; infrequent: epistaxis, bronchitis, asthma, pneumonia; rare: asphyxia, laryngitis, pneumothorax, hiccup.
 * frequent: pruritus, rash
 * infrequent: acne, exfoliative dermatitis, dry skin, herpes simplex, alopecia
 * rare: urticaria, herpes zoster, skin hypertrophy, seborrhea, skin ulcer.
 * infrequent: eye pain, abnormality of accommodation, conjunctivitis, deafness, keratoconjunctivitis, lacrimation disorder, glaucoma, hyperacusis, ear pain
 * rare: blepharitis, partial transitory deafness, otitis media, taste loss, parosmia.
 * frequent: urinary tract infection
 * infrequent: kidney calculus, cystitis, dysuria, urinary incontinence, urinary retention, vaginitis, hematuria, breast pain, amenorrhea, dysmenorrhea, leukorrhea, impotence
 * rare: polyuria, urethritis, metorrhagia, menorrhagia, abnormal ejaculation, breast engorgement, breast enlargement, urinary urgency.

Adverse events observed during the post-marketing evaluation
Adverse events reported since market introduction, which were temporally (but not necessarily causally) related to Mirtazapine therapy, include four cases of the ventricular arrhythmia torsades de pointes. In three of the four cases, however, concomitant drugs were implicated. All patients recovered. Return to top