The first of a new class of antidepressants – the alpha2-receptor antagonists – has received FDA approval for the treatment of depression. Mirtazapine (Remeron / Akzo Nobel, Organon) is a long-acting tetracyclic compound unrelated to the tricyclic antidepressants. It is a potent antagonist of central pre- and post-synaptic alpha2-adrenergic receptors and also serotonin (5-HT2 and 5-HT3) and histamine (H1) receptors, and has a moderate effect on peripheral alpha1 adrenergic receptors. Antagonizing histamine receptors explains its prominent sedative effect, and antagonizing peripheral adrenergic receptors explains its tendency to cause orthostatic hypotension.
In clinical trials involving 4,562 patients with major depression (2,796 on mirtazapine (Remeron), 605 on placebo, and 1,161 on other antidepressants), mirtazapine (Remeron) was superior to placebo and at least as effective as other antidepressants for relieving symptoms of depression: dysphoric mood, loss of interest in daily activities, weight change, insomnia or hypersomnia, agitation or retardation, impaired concentration, and suicidal ideation. During the 6-week trials, almost half of patients treated with mirtazapine (Remeron) (20-30 mg/day) showed improvements of 50% or more; antidepressant effect usually appeared in 1-4 weeks.
The most common side effect in clinical trials was somnolence, which was reported by 54% of mirtazapine-treated patients compared with 60% of amitriptyline-treated patients and 18% of placebo-treated patients. Other side effects were orthostatic hypotension, increased appetite and weight gain, dry mouth, constipation, increase in cholesterol and triglyceride levels, increase in liver enzyme levels, neutropenia, and agranulocytosis. The most serious side effect was agranulocytosis, which occurred in three of the 2796 mirtazapine-treated patients (absolute granulocyte count less than 500/ mm3). Two patients had associated symptoms (fever, infection) and one had no associated symptoms.
Mirtazapine (Remeron) is rapidly and completely absorbed orally, with peak plasma concentrations achieved within about 2 hours of dosing (food in the stomach has a minimal affect on absorption). Absolute bioavailability is about 50%. Mirtazapine (Remeron) is approximately 85% plasma protein bound, extensively metabolized in the liver, and excreted in the urine. Elimination half life is 20-40 hours, although females have a considerably longer half-life (mean 37 hours) than males (mean 26 hours). Mirtazapine (Remeron) should be used with caution in patients with compromised hepatic function (clearance is reduced approximately 30% in patients with liver disease) or compromised renal function (clearance is reduced 30% in patients with moderate kidney disease and 50% with severe kidney disease). Clearance is also reduced in elderly patients (in clinical trials, clearance was 40% lower in elderly males than in younger males, and 10% lower in elderly females than younger females).
Available in 15 and 30 mg tablets, mirtazapine (Remeron) is given once daily (preferably at bedtime) in a dose of 15 mg/day initially, increased incrementally (every 1-2 weeks) to a maximum of 45 mg/day. Patients should be advised to report any signs of infection (sore throat, fever, stomatitis), and the drug should be discontinued if symptoms are accompanied by depressed white blood cell count. Patients should also be advised that sedation could interfere with cognitive and motor performance, and that alcohol will increase somnolence. Because monoamine-oxidase inhibitors (MAOIs) have been associated with serious or even fatal reactions when combined with other antidepressants, MAOIs should not be used in combination with mirtazapine (Remeron). Mirtazapine (Remeron) is not a potent inhibitor of cytochrome P450 enzymes, but drugs which are may alter the metabolism, and hence the activity, of mirtazapine (Remeron).
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Hello, everybody, who is interested to be healthy. My name is Kelly. I learnt about depression by my own experience. Now I am ok. Here I want to share my thoughts and ideas how to treat depression symptoms.