Depression Symptoms Treatment

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Buy Mirtazapine Online Without Prescription

Mirtazapine is authorised in the world under the following brand names: Avanza, Axit, Mirtabene, Mirtaz, Mirtazon, Norset, Promyrtil, Remergil, Remergon, Remeron, Remeron Soltab, Rexer, Zispin.

Mirtazapine (Remeron / Organon) was approved by the U.S. Food and Drug Administration in 1996 for the treatment of depression. Structurally unrelated to any antidepressants currently available in the United States, it is a tetracyclic piperazinoazepine and is an analog of mianserin (available outside the U.S.).

Mechanism of Action Mirtazapine (Remeron) appears to exert its antidepressant effect in a unique way. It blocks central presynaptic alpha2-adrenergic receptors, which results in an increased release of norepinephrine and serotonin. In addition, it strongly blocks serotonergic 5-hydroxytryptamine (5-HT2 and 5-HT3) and histaminic H1 receptors and weakly blocks peripheral alpha1-adrenergic and muscarinic receptors.

Pharmacokinetics Mirtazapine (Remeron) Following oral absorption, mirtazapine is rapidly and completely absorbed, with peak plasma levels achieved within about two hours; neither the rate nor extent of absorption is significantly affected by food. It is extensively metabolized in the liver, by the cytochrome P450 isoenzymes 2D6, 1A2, and 3A4, primarily to inactive metabolites, and excreted mainly in urine. Its half-life of elimination is between 20 and 40 hours, which implies that steady state levels at a given dose would be achieved within approximately five days, and it exhibits about 85% plasma protein-binding.

Clinical Trials Mirtazapine (Remeron) The results of four six-week, double-blind studies of Mirtazapine (Remeron) in the treatment of major depression have been reported in the literature. In a trial of 90 outpatients with major depression, 50% of patients taking mirtazapine (10–35 mg/day) improved, compared with 28% of patients taking placebo. By the end of the study, 18 of the mirtazapine and 26 of the placebo patients had dropped out.

In two studies, mirtazapine was compared with amitriptyline. In the earlier of the two, 90 of 150 patients completed the six-week study. The average daily dose of mirtazapine was 18 mg and that of amitriptyline was 111 mg. Of the completers, 63% of the patients improved with mirtazapine, 69% with amitriptyline and 48% with placebo.4 In the other study, improvement was seen in 70%, 58% and 33% of patients treated with mirtazapine (average daily dose of 22 mg), amitriptyline (average daily dose of 133 mg), and placebo, respectively.5 Overall, the high dropout rates and questionable therapeutic amitriptyline doses make the results of these studies difficult to interpret.

In a study of 200 hospitalized patients comparing Mirtazapine (Remeron) (24–72 mg/day) with trazodone (150–450 mg/day), mirtazapine was shown to be significantly more effective than trazodone.

No trials have been published comparing Mirtazapine (Remeron) with any of the selective serotonin reuptake inhibitors (e.g., fluoxetine, sertraline, paroxetine), nor has there been systematic investigation of its efficacy over the long-term (i.e., six or more months) treatment period required for a major depressive episode.

Adverse Effects and Toxicity The most common adverse effect reported with Mirtazapine (Remeron) is transient somnolence, which occurs in at least 50% of patients, followed by increased appetite and weight gain, dizziness, dry mouth and constipation, all of which would be expected based on the drug’s pharmacologic profile (see Table 1). In premarketing trials, two of 2,796 patients who received mirtazapine developed agranulocytosis and one developed severe neutropenia. Nonfasting cholesterol levels increased to 20% or more above the upper limits of normal in 15% and increases in aminotransferase activity occurred in 2% of patients treated with Mirtazapine (Remeron). No clinically significant electrocardiographic changes have been reported.

An 81-year-old woman was admitted to intensive care in a semi-comatose state following ingestion (according to family members) of sixty 15-mg mirtazapine tablets and fourteen 15-mg Mirtazapine (Remeron) tablets the day prior to admission. Within an hour, the patient awoke with only one side effect, somnolence, which dissipated over three days. No significant effects were noted in cardiopulmonary function, and no seizures were observed. If this case reflects what can be generally expected with overdose, mirtazapine appears to be relatively safe.

Drug Interaction Mirtazapine (Remeron) is a substrate of cytochrome P450 isoenzymes 2D6, 1A2, and 3A4; however, it does not appear to inhibit these isoenzymes. Although no systematic studies of isoenzyme-related interactions have been completed, it is reasonable to expect that mirtazapine would have little, if any, effect on drugs metabolized by isoenzymes 2D6, 1A2, or 3A4; on the other hand, concomitant use of inhibitors or inducers of these enzymes could respectively increase or decrease blood levels of mirtazapine. Mirtazapine (Remeron) in combination with benzodiazepines or ethanol may result in additive effects with respect to sedation and psychomotor impairment. Since concurrent use of mirtazapine and monoamine oxidase inhibitors (MAOIs) could theoretically lead to a hypertensive crisis (due to noradrenergic excess) or a serotonin syndrome (due to serotonergic excess), the manufacturer recommends that the two not be used in combination and that there be at least a 14-day washout period between discontinuation of an MAOI and initiation of mirtazapine or the reverse.

Dosage Mirtazapine (Remeron) The recommended starting dose of mirtazapine (available in 15- and 30-mg scored tablets) is 15 mg/day, at bedtime. This can be increased at intervals of one to two weeks up to a maximum dose of 45 mg/day. Reduced dosages may be necessary in the elderly and in patients with moderate to severe renal or hepatic disease.

Conclusion Mirtazapine’s chemical structure and mechanism of action are unique among the antidepressants. However, from the mid-1980s to the mid-1990s, a major goal in the development of new antidepressants was to find agents very specific and narrow in their pharmacologic actions (e.g., only affecting serotonin); ironically, mirtazapine has “mixed” activity with respect to actions on central norepinephrine and serotonin, and on other receptor systems. More must be known about the benefits versus the disadvantages of this “mixed” activity and the incidence of agranulocytosis and neutropenia, as well as the drug’s toxicity profile and short-term and long-term efficacy as compared with other newer antidepressants, to determine where the drug fits into our antidepressant armamentarium.