Mirtazapine (Tablet, Orally Disintegrating)

Mirtazapine (Tablet, Orally Disintegrating)

Mirtazapine orally disintegrating tablets are an orally administered drug. Mirtazapine has a tetracyclic chemical structure and belongs to the piperazino-azepine group of compounds. It is designated 1,2,3,4,10,14b-hexahydro-2-methylpyrazino[2,1-a]pyrido[2,3-c] benzazepine. The structural formula is the following and it is the racemic mixture: CHNM.W. 265.36 Mirtazapine is a white to creamy white crystalline powder which is slightly soluble in water. Mirtazapine is available for oral administration as an orally disintegrating tablet containing 15, 30, or 45 mg of mirtazapine. It disintegrates in the mouth within seconds after placement on the tongue allowing its contents to be subsequently swallowed with or without water. Mirtazapine orally disintegrating tablets also contain the following inactive ingredients: ascorbic acid, aspartame, BHT, citric acid, concentrated orange juice, corn syrup, crospovidone, dextrin, eudragit E100, FD&C Yellow #6, magnesium stearate, mannitol, modified food starch, natural ethyl butyrate, oil lemon, oil orange, oil orange essence, oil tangerine, potassium sorbate, silicon dioxide, sodium benzoate, turmeric extract, xylitol.

dailymed-ingredient:Mirtazapine

Mirtazapine orally disintegrating tablets are available as follows: 15 mg Tablets���White to off-white, round, flat bevelled edge tablets. One side of the tablet debossed with the number���93���. The other side of the tablet debossed with the number���7303���. They are available in boxes of 30 (5 x 6 unit dose blisters). 30 mg Tablets���White to off-white, round, flat bevelled edge tablets. One side of the tablet debossed with the number���93���. The other side of the tablet debossed with the number���7304���. They are available in boxes of 30 (5 x 6 unit dose blisters). 45 mg Tablets���White to off-white, round, flat bevelled edge tablets. One side of the tablet debossed with the number���93���. The other side of the tablet debossed with the number���7305���. They are available in boxes of 30 (10 x 3 unit dose blisters).<br/>Storage: Store at 20��to 25��C (68��to 77��F) [See USP Controlled Room Temperature]. Protect from light and moisture. Use immediately upon opening individual tablet blister.

Suicidality and Antidepressant Drugs: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of mirtazapine orally disintegrating tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Mirtazapine orally disintegrating tablets are not approved for use in pediatric patients. (See WARNINGS, Clinical Worsening and Suicide Risk, PRECAUTIONS, Information for Patients, and PRECAUTIONS, Pediatric Use.) Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in thosereceiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials.

dailymed-ingredient:BHT, dailymed-ingredient:FD&C_Yellow_#6, dailymed-ingredient:ascorbic_acid, dailymed-ingredient:aspartame, dailymed-ingredient:citric_acid, dailymed-ingredient:concentrated_orange_juice, dailymed-ingredient:corn_syrup, dailymed-ingredient:crospovidone, dailymed-ingredient:dextrin, dailymed-ingredient:eudragit_E100, dailymed-ingredient:magnesium_stearate, dailymed-ingredient:mannitol, dailymed-ingredient:modified_food_starch, dailymed-ingredient:natural_ethyl_butyrate, dailymed-ingredient:oil_lemon, dailymed-ingredient:oil_orange, dailymed-ingredient:oil_orange_essence, dailymed-ingredient:oil_tangerine, dailymed-ingredient:potassium_sorbate, dailymed-ingredient:silicon_dioxide, dailymed-ingredient:sodium_benzoate, dailymed-ingredient:turmeric_extract, dailymed-ingredient:xylitol

General:<br/>Somnolence: In U.S. controlled studies, somnolence was reported in 54% of patients treated with mirtazapine tablets, compared to 18% for placebo and 60% for amitriptyline. In these studies, somnolence resulted in discontinuation for 10.4% of mirtazapine-treated patients, compared to 2.2% for placebo. It is unclear whether or not tolerance develops to the somnolent effects of mirtazapine. Because of mirtazapine's potentially significant effects on impairment of performance, patients should be cautioned about engaging in activities requiring alertness until they have been able to assess the drug's effect on their own psychomotor performance (see Information for Patients).<br/>Dizziness: In U.S. controlled studies, dizziness was reported in 7% of patients treated with mirtazapine, compared to 3% for placebo and 14% for amitriptyline. It is unclear whether or not tolerance develops to the dizziness observed in association with the use of mirtazapine.<br/>Increased Appetite/Weight Gain: In U.S. controlled studies, appetite increase was reported in 17% of patients treated with mirtazapine, compared to 2% for placebo and 6% for amitriptyline. In these same trials, weight gain of���7% of body weight was reported in 7.5% of patients treated with mirtazapine, compared to 0% for placebo and 5.9% for amitriptyline. In a pool of premarketing U.S. studies, including many patients for long-term, open label treatment, 8% of patients receiving mirtazapine discontinued for weight gain.<br/>Cholesterol/Triglycerides: In U.S. controlled studies, nonfasting cholesterol increases to���20% above the upper limits of normal were observed in 15% of patients treated with mirtazapine, compared to 7% for placebo and 8% for amitriptyline. In these same studies, nonfasting triglyceride increases to���500 mg/dL were observed in 6% of patients treated with mirtazapine, compared to 3% for placebo and 3% for amitriptyline.<br/>Transaminase Elevations: Clinically significant ALT (SGPT) elevations (���3 times the upper limit of the normal range) were observed in 2.0% (8/424) of patients exposed to mirtazapine in a pool of short-term U.S. controlled trials, compared to 0.3% (1/328) of placebo patients and 2.0% (3/181) of amitriptyline patients. Most of these patients with ALT increases did not develop signs or symptoms associated with compromised liver function. While some patients were discontinued for the ALT increases, in other cases, the enzyme levels returned to normal despite continued mirtazapine treatment. Mirtazapine orally disintegrating tablets should be used with caution in patients with impaired hepatic function (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).<br/>Activation of Mania/Hypomania: Mania/hypomania occurred in approximately 0.2% (3/1299 patients) of mirtazapine-treated patients in U.S. studies. Although the incidence of mania/hypomania was very low during treatment with mirtazapine, it should be used carefully in patients with a history of mania/hypomania.<br/>Seizure: In premarketing clinical trials only one seizure was reported among the 2796 U.S. and non-U.S. patients treated with mirtazapine. However, no controlled studies have been carried out in patients with a history of seizures. Therefore, care should be exercised when mirtazapine is used in these patients.<br/>Use in Patients with Concomitant Illness: Clinical experience with mirtazapine orally disintegrating tablets in patients with concomitant systemic illness is limited. Accordingly, care is advisable in prescribing mirtazapine for patients with diseases or conditions that affect metabolism or hemodynamic responses. Mirtazapine orally disintegrating tablets have not been systematically evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or other significant heart disease. Mirtazapine was associated with significant orthostatic hypotension in early clinical pharmacology trials with normal volunteers. Orthostatic hypotension was infrequently observed in clinical trials with depressed patients. Mirtazapine orally disintegrating tablets should be used with caution in patients with known cardiovascular or cerebrovascular disease that could be exacerbated by hypotension (history of myocardial infarction, angina, or ischemic stroke) and conditions that would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medication). Mirtazapine clearance is decreased in patients with moderate [glomerular filtration rate (GFR) = 11 to 39 mL/min/1.73 m] and severe [GFR<10 mL/min/1.73 m] renal impairment, and also in patients with hepatic impairment. Caution is indicated in administering mirtazapine orally disintegrating tablets to such patients (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).<br/>Information for Patients: Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with mirtazapine orally disintegrating tablets and should counsel them in its appropriate use. A patient Medication Guide about���Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal Thoughts or Actions���is available for mirtazapine orally disintegrating tablets. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document. Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking mirtazapine orally disintegrating tablets.<br/>Clinical Worsening and Suicide Risk: Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to look for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient's prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication.<br/>Agranulocytosis: Patients who are to receive mirtazapine orally disintegrating tablets should be warned about the risk of developing agranulocytosis. Patients should be advised to contact their physician if they experience any indication of infection such as fever, chills, sore throat, mucous membrane ulceration or other possible signs of infection. Particular attention should be paid to any flu-like complaints or other symptoms that might suggest infection.<br/>Interference with Cognitive and Motor Performance: Mirtazapine orally disintegrating tablets may impair judgement, thinking, and particularly, motor skills, because of its prominent sedative effect. The drowsiness associated with mirtazapine use may impair a patient's ability to drive, use machines or perform tasks that require alertness. Thus, patients should be cautioned about engaging in hazardous activities until they are reasonably certain that mirtazapine orally disintegrating tablet therapy does not adversely affect their ability to engage in such activities.<br/>Completing Course of Therapy: While patients may notice improvement with mirtazapine orally disintegrating tablet therapy in 1 to 4 weeks, they should be advised to continue therapy as directed.<br/>Concomitant Medication: Patients should be advised to inform their physician if they are taking, or intend to take, any prescription or over-the-counter drugs since there is a potential for mirtazapine orally disintegrating tablets to interact with other drugs.<br/>Alcohol: The impairment of cognitive and motor skills produced by mirtazapine has been shown to be additive with those produced by alcohol. Accordingly, patients should be advised to avoid alcohol while taking any dosage form of mirtazapine.<br/>Phenylketonurics: Phenylketonuric patients should be informed that mirtazapine orally disintegrating tablets contain phenylalanine 2.02 mg per 15 mg tablet, 4.04 mg per 30 mg tablet, and 6.06 mg per 45 mg tablet.<br/>Pregnancy: Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during mirtazapine orally disintegrating tablet therapy.<br/>Nursing: Patients should be advised to notify their physician if they are breast-feeding an infant.<br/>Laboratory Tests: There are no routine laboratory tests recommended.<br/>Drug Interactions: As with other drugs, the potential for interaction by a variety of mechanisms (e.g., pharmacodynamic, pharmacokinetic inhibition or enhancement, etc.) is a possibility (see CLINICAL PHARMACOLOGY).<br/>Drugs Affecting Hepatic Metabolism: The metabolism and pharmacokinetics of mirtazapine orally disintegrating tablets may be affected by the induction or inhibition of drug-metabolizing enzymes.<br/>Drugs that are Metabolized by and/or Inhibit Cytochrome P450 Enzymes: Many drugs are metabolized by and/or inhibit various cytochrome P450 enzymes, e.g., 2D6, 1A2, 3A4, etc. In vitro studies have shown that mirtazapine is a substrate for several of these enzymes, including 2D6, 1A2, and 3A4. While in vitro studies have shown that mirtazapine is not a potent inhibitor of any of these enzymes, an indication that mirtazapine is not likely to have a clinically significant inhibitory effect on the metabolism of other drugs that are substrates for these cytochrome P450 enzymes, the concomitant use of mirtazapine orally disintegrating tablets with most other drugs metabolized by these enzymes has not been formally studied. Consequently,it is not possible to make any definitive statements about the risks of coadministration of mirtazapine orally disintegrating tablets with such drugs.<br/>Alcohol: Concomitant administration of alcohol (equivalent to 60 g) had a minimal effect on plasma levels of mirtazapine (15 mg) in 6 healthy male subjects. However, the impairment of cognitive and motor skills produced by mirtazapine was shown to be additive with those produced by alcohol. Accordingly, patients should be advised to avoid alcohol while taking mirtazapine orally disintegrating tablets.<br/>Diazepam: Concomitant administration of diazepam (15 mg) had a minimal effect on plasma levels of mirtazapine (15 mg) in 12 healthy subjects. However, the impairment of motor skills produced by mirtazapine tablets has been shown to be additive with those caused by diazepam. Accordingly, patients should be advised to avoid diazepam and other similar drugs while taking mirtazapine orally disintegrating tablets.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility:<br/>Carcinogenesis: Carcinogenicity studies were conducted with mirtazapine given in the diet at doses of 2, 20, and 200 mg/kg/day to mice and 2, 20, and 60 mg/kg/day to rats. The highest doses used are approximately 20 and 12 times the maximum recommended human dose (MRHD) of 45 mg/day on a mg/mbasis in mice and rats, respectively. There was an increased incidence of hepatocellular adenoma and carcinoma in male mice at the high dose. In rats, there was an increase in hepatocellular adenoma in females at the mid and high doses and in hepatocellular tumors and thyroid follicular adenoma/cystadenoma and carcinoma in males at the high dose. The data suggest that the above effects could possibly be mediated by non-genotoxic mechanisms, the relevance of which to humans is not known. The doses used in the mouse study may not have been high enough to fully characterize the carcinogenic potential of mirtazapine tablets.<br/>Mutagenesis: Mirtazapine was not mutagenic or clastogenic and did not induce general DNA damage as determined in several genotoxicity tests: Ames test, in vitro gene mutation assay in Chinese hamster V 79 cells, in vitro sister chromatid exchange assay in cultured rabbit lymphocytes, in vivo bone marrow micronucleus test in rats, and unscheduled DNA synthesis assay in HeLa cells.<br/>Impairment of Fertility: In a fertility study in rats, mirtazapine was given at doses up to 100 mg/kg [20 times the maximum recommended human dose (MRHD) on a mg/mbasis]. Mating and contraception were not affected by the drug, but estrous cycling was disrupted at doses that were 3 or more times the MRHD and pre-implantation losses occurred at 20 times the MRHD.<br/>Pregnancy:<br/>Teratogenic Effects:<br/>Nursing Mothers: It is not known whether mirtazapine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when mirtazapine orally disintegrating tablets are administered to nursing women.<br/>Pediatric Use: Safety and effectiveness in the pediatric population have not been established (see BOX WARNING and WARNINGS, Clinical Worsening and Suicide Risk). Two placebo-controlled trials in 258 pediatric patients with MDD have been conducted with mirtazapine, and the data were not sufficient to support a claim for use in pediatric patients. Anyone considering the use of mirtazapine orally disintegrating tablets in a child or adolescent must balance the potential risks with the clinical need.<br/>Geriatric Use: Approximately 190 elderly individuals (���65 years of age) participated in clinical studies with mirtazapine tablets. This drug is known to be substantially excreted by the kidney (75%), and the risk of decreased clearance of this drug is greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Sedating drugs may cause confusion and over-sedation in the elderly. No unusual adverse age-related phenomena were identified in this group. Pharmacokinetic studiesrevealed a decreased clearance in the elderly. Caution is indicated in administering mirtazapine orally disintegrating tablets to elderly patients (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

Mirtazapine

Associated with Discontinuation of Treatment: Approximately 16 percent of the 453 patients who received mirtazapine tablets 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:<br/>Commonly Observed Adverse Events in U.S. Controlled Clinical Trials: The most commonly observed adverse events associated with the use of mirtazapine tablets (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:<br/>Adverse Events Occurring at an Incidence of 1% or More Among Mirtazapine-Treated Patient: The table 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 tablets-treated patients who participated in short-term U.S. placebo-controlled 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 one 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 non-drug factors to the side effect incidence rate in the population studied.<br/>ECG Changes: The electrocardiograms for 338 patients who received mirtazapine tablets 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.<br/>Other Adverse Events Observed During the Premarketing Evaluation of Mirtazapine: During its premarketing assessment, multiple doses of mirtazapine tablets 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 similartypes 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 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 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients. Only those events not already listed in the previous table 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. 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, 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. 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, 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.<br/>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 four cases of the ventricular arrhythmia torsade de pointes. In three of the four cases, however, concomitant drugs were implicated. All patients recovered.

Mirtazapine orally disintegrating tablets are indicated for the treatment of major depressive disorder. The efficacy of mirtazapine tablets in the treatment of major depressive disorder was established in six week controlled trials of outpatients whose diagnoses corresponded most closely to the Diagnostic and Statistical Manual of Mental Disorders���3rd edition (DSM-III) category of major depressive disorder (see CLINICAL PHARMACOLOGY). A major depressive episode (DSM-IV) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least five of the following nine symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotoragitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt or suicidal ideation. The effectiveness of mirtazapine orally disintegrating tablets in hospitalized depressed patients has not been adequately studied. The efficacy of mirtazapine in maintaining a response in patients with major depressive disorder for up to 40 weeks following 8 to 12 weeks of initial open-label treatment was demonstrated in a placebo-controlled trial. Nevertheless, the physician who elects to use mirtazapine for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient (see CLINICAL PHARMACOLOGY).

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