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Mirtazapine increases noradrenergic and serotonergic transmission, as measured by on-line microdialysis and by enhancement of noradrenergic locus ceruleus and serotonergic raphe nucleus cell firing. The enhancement of both noradrenergic and serotonergic transmission probably underlies the therapeutic activity of mirtazapine. Subjectively, mirtazapine induced an improvement of sleep. The aim of the locomotor activity test was to select a dose which had no influence on the motility of the animals and, at the same time, was active at least in one behavioral test. In the maze test, mirtazapine shortened the food finding time (it improved memory) and counteracted memory loss induced by scopolamine. Moreover, citalopram still inhibited, and mirtazapine still failed to influence, dorsal raphe serotonergic neurons.
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In rats chronically treated with imipramine or mirtazapine this effect was completely antagonized. These results demonstrate that long-term treatment with either imipramine or mirtazapine reduces the sensitivity of cortical cholinergic neurons to stress or to an anxiogenic drug with an efficacy similar to that of acute administration of benzodiazepines. Because dopaminergic transmission in the prefrontal cortex is sensitive to anxiogenic or stressful stimuli, the effects of two antidepressant drugs with different mechanisms of action, imipramine and mirtazapine, on the response of rat cortical dopaminergic neurons to stress were investigated. Long-term administration of imipramine or mirtazapine had no marked effect on the stress-induced increases in the brain or plasma concentrations of neuroactive steroids or corticosterone. In depressed patients, mirtazapine produces a significant shortening of sleep-onset latency, increases a total sleep time, and leads to a marked improvement in sleep efficiency. Mirtazepine is a potential alternative anti-depressant with multiple additional benefits. It is becoming increasingly clear that differences exist between antidepressants with respect to this property, both within and between pharmacologic classes.
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The positive predictive value of an early improvement was significantly higher during mirtazapine treatment compared with paroxetine. Mirtazapine was consistently superior to placebo, and equivalent in efficacy to the tricyclic antidepressants amitriptyline, doxepin and clomipramine, but with an improved tolerability profile. In addition, mirtazapine does not appear to be associated with sexual dysfunction. Mirtazapine in fixed and ascending nocturnal dosing regimens was found to facilitate sleep, but it does not generally reduce daytime alertness. Mirtazapine did not significantly alter rapid eye movement sleep parameters. The available data show that mirtazapine is superior to placebo in depressed patients with high baseline anxiety and/or agitation. Mirtazapine provides early and effective relief of both depressive and anxiety symptoms, reducing the need for polypharmacy.
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The evaluation of the safety was based on data from all patients who took at least one dose of study medication during studies comparing mirtazapine with placebo, amitriptyline or other active comparators. These complaints were typically mild and transient in nature, and decreased over time despite increased doses of mirtazapine. The low seizure-inducing potential combined with a lack of cardiotoxic properties allows safety in an overdose of mirtazapine, even in elderly patients. Weight gain is the most commonly reported side-effect of mirtazapine, although there is evidence to suggest that this is not a significant problem during long-term treatment.
However, the different pharmacologic profile of mirtazapine is reflected in its different tolerability profile. Among antidepressants, amitriptyline and mirtazapine are known to cause weight gain. Mirtazapine also appears to be associated with a low rate of sexual adverse effects. In a comparison between mirtazapine and fluoxetine, initial treatment with fluoxetine is less expensive with respect to direct cost, but these two alternatives are equivalent when indirect costs are taken into consideration. Additionally, we want it to investigate the effects of different antidepressant medication (mirtazapine, venlafaxine, tianeptine and escitalopram) on oxidative status of depressed patients.
Mirtazapine is an atypical antidepressant receiving attention for substance abuse pharmacotherapy, and its action includes alterations in monoaminergic transmission. Collectively, these results indicate that mirtazapine may help to maintain abstinence in opioid dependent patients. This biochemical and histologic study investigated a possible protective effect of mirtazapine with regard to cisplatin-induced nephrotoxicity in the rat. Notably, better survival rates and intervals were also found in mirtazapine-treated mice.