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Summary
Abstract
Mirtazapine (Remeron®, Zispin®) is a noradrenergic and specific serotonergic antidepressant (NaSSA) that is approved in many counties for use in the treatment of major depression. Monotherapy with mirtazapine 1 5-45 mg/day leads to rapid and sustained improvements in depressive symptoms in patients with major depression, including the elderly. It is as effective as other antidepressants and may have a more rapid onset of action than selective serotonin reuptake inhibitors (SSRIs). Furthermore, it may also have a higher sustained remission rate than amitriptyline. Preliminary data suggest that mirtazapine may also be effective in the treatment of anxiety disorders (including post-traumatic stress disorder, panic disorder and social anxiety disorder), obsessive-compulsive disorder, undifferentiated somatoform disorder and, as add-on therapy, in schizophrenia, although large, well designed trials are needed to confirm these findings. Mirtazapine is generally well tolerated in patients with depression. In conclusion, mirtazapine is an effective antidepressant for the treatment of major depression and also has the potential to be of use in other psychiatric indications.
Pharmacological Properties
The antidepressant activity of mirtazapine, an NaSSA agent, is thought to result from a combination of noradrenergic and serotonergic effects, with the latter specifically involving enhancement of serotonin 5-HT^sub 1^ receptor-mediated effects. It acts as an antagonist at central α^sub 2^-adrenergic autoreceptors and heteroreceptors, and postsynaptic 5-HT^sub 2^ and 5-HT^sub 3^ receptors. Mirtazapine has low affinity for central and peripheral dopaminergic receptors, but is a potent antagonist of histamine H^sub 1^ receptors and a moderate antagonist at muscarinic receptors. Mirtazapine improves sleep efficiency and continuity, and does not suppress rapid eye movement sleep.
Mirtazapine is absorbed rapidly after oral administration, with peak plasma concentrations achieved within 2 hours. Food has no clinically relevant effect on absorption. Mirtazapine displays linear pharmacokinetics over the therapeutic dosage range, and steady state is reached after =5 days. Mirtazapine is extensively metabolized, principally via cytochrome P450 (CYP) isoenzymes CYP3A4, CYP2D6 and CYPl A2. The elimination half-life of mirtazapine is 20-40 hours. Mirtazapine is a racemate and the enantiomers display differing pharmacokinetic and pharmacodynamic properties; both enantiomers contribute to the pharmacodynamic effects of mirtazapine.
Therapeutic Efficacy
A number of well designed trials have demonstrated the efficacy of mirtazapine in the treatment of patients with moderate to severe major depression. Mirtazapine was more...