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International Neurological Journal 4 (14) 2007

Mirtazapine – a new generation of antidepressant

Authors: SG Burchinsky, Institute of Gerontology AMS of UK, Kyiv
Categories: Neurology
Categories: Clinical Research

The article describes the mechanism of action of new generation antidepressants – mirtazapine, the comparative characteristic effects of this medication with other antidepressants, widely used in clinical practice. Separately considered the use of mirtazapine in geriatric practice and drug safety issues.

depressive disorders, Mirtazapine.

One of the major problems of modern psychiatry are depressive disorders, taking into account both the frequency of their development in the modern population (10%), as well as their social, economic and psychological significance, and the role of disability in the population. Accordingly, it is particularly relevant in this context is the search for high-performance tools pharmacotherapy of depression ; New drugs of antidepressant drugs.

Antidepressants are now one of the most rapidly developing group of psychotropic drugs. For example, U.S. first place they occupy both the number of new compounds studied, and the volume of investment in new drugs [19].

Given the importance of depressive disorders in terms of their enormous role in the structure of morbidity, disability and economic costs to them in developed countries, especially important to the evolution of the clinical picture of depression observed in recent decades, namely:

1) The increase in the number of atypical, erased, comorbid clinical forms;

2) an increase in the frequency and severity of relapses;

3) increased resistance to treatment drugs Convention’s group of antidepressants ; tricyclic (TCA) and selective serotonin reuptake inhibitors (SSRIs).

In addition, separately necessary to distinguish a trend towards more frequent polypharmacy in the treatment of depression by increasing the number of parallel received psycho – and somatotropic funds, as well as the deterioration of the tolerance of many first-generation drugs, especially TAD [4, 31].

In this connection, in Psychopharmacology it became necessary to develop new antidepressants, on the one hand, with the advanced mode of action, including effects on various neurotransmitter systems, and, accordingly, a wider range of clinical – the pharmacological effects, but with different ; preserving the pronounced selectivity of the impact on the individual links synaptic structural – functional organization and, therefore, characterized by a high level of safety.

In this regard, special attention should be given antidepressant drugs group with a fundamentally different mechanism of action compared to the first generation, that is, preparations not influence the system monoamine reuptake, and different receptor structures. One such drug is mirtazapine ; chetyrehtsiklicheskoe derivative, noradrenergic and selective serotonergic antidepressant (NACA), the establishment of which marked a new stage in the development of the pharmacology of these funds.

Mirtazapine ; an antidepressant with a unique mechanism of action. Unlike the TAD and SSRI drugs it does not affect the reuptake of serotonin, norepinephrine and dopamine. This drug selectively blocks alpha – 2 – auto – and geteroadrenoretseptory and serotonin 5 – HT – 2 – and 5 – HT – 3 – receptors.

What is the interest of such a mechanism of action in terms of pharmacotherapy of depression?

As is known, the activation of alpha – 2 – autoadrenoretseptorov, located on the presynaptic terminals of adrenergic neurons through a feedback mechanism reduces the release of norepinephrine and synaptic nerve terminal, respectively, adrenergic inhibition implement processes in the brain. At the same time, alpha – 2 – geteroadrenoretseptory located on terminals of serotonergic neurons and their activation also influences serotonergic weakens in the CNS. Thus, blockade of both types of receptors referred to as serotonin contributes to activation – and adrenergic processes, i.e. provides a mechanism for implementation of the antidepressant effect [7, 16, 26].

addition, mirtazapine blocks 5 – HT – 2 – 5 and – NT – 3 – receptors, which binds to the activation of undesired side effects of TAJ and SSRIs, including serotonin syndrome, agitation, anxiety, sexual dysfunction, diarrhea disorders, headache and others. [27]. At the same time stimulates mirtazapine 5 – NT – 1 – receptors, that is realized through proper antidepressant and anxiolytic action of serotonin [8, 12].

Thus, mirtazapine has a high degree of selectivity to serotonin effect – adrenergic and processes in the brain. It is important to emphasize that this selectivity is manifested not only the receptor but also at the system level, contributing to the activation of serotonin – and adrenergic reactions, the most significant in terms of depression pharmacotherapy.

In addition, mirtazapine has the properties of the central histaminergic blocker H1 – receptors, slightly anticholinergic properties and exhibits almost no effect on the dopaminergic processes [16, 24].

As a result, clinical – pharmacological spectrum of action of mirtazapine is characterized by the following main features:

1) the presence of the expressed timoanalepticheskogo and anxiolytic action;

2) the most rapid onset of clinical effect (already at 1 – week of treatment);

3) the presence of sedation and normalization of sleep.

In clinical practice, the use of mirtazapine was the most effective in anxiety – depressive disorders, including patients with severe agitation, anxiety, sleep disorders [2, 6, 7, 18, 21]. It is particularly important to underline the effectiveness of mirtazapine in severe depression, as well as clinical forms resistant to the conventional therapy (TAD and SSRIs) [5, 7, 16, 29]. In addition, given the low potential of drug-drug interaction of mirtazapine, in some cases with severe refractory depression expedient combination of mirtazapine and venlafaxine as the drugs effectively complementary to the pharmacological and clinical point of view [17].

One of the major clinical benefits of mirtazapine is an early start timoanalepticheskogo and anxiolytic action. In carrying out various studies on the effectiveness of mirtazapine compared to paroxetine, citalopram, fluoxetine was found significantly greater efficacy of mirtazapine in the 1 – 4 – the first week of treatment, as well as higher rates of response to therapy [7, 16, 34]. When compared with amitriptyline mirtazapine exhibits comparable efficiency, however patients receiving mirtazapine, number of relapses (2 – year study) was smaller and the stability of remission is greater than amitriptyline treatment [33].

It is important to emphasize that in the spectrum of clinical effects of mirtazapine there is a positive effect on the symptoms of depression, it is extremely difficult-to-correct other antidepressants, ; anhedonia, psychomotor retardation, as well as cyclothymic disorder.

Thus, mirtazapine showed himself to be an effective antidepressant for the treatment of both acute depressive episode, and as part of maintenance therapy. In addition to the anxiolytic profile of the drug, of particular note are its normalizing effect on sleep.

Sleep disturbances in depression ; One of the most common diagnostic symptoms of this disease is reflected in the DSM – IV [13] and observed in 80 – 90% of depressed patients. They include disorders of sleep and waking, as well as disruption of sleep patterns. In most cases, there is a clear correlation between the severity of the affective component and the severity of insomnia. [9] In this sleep disorder may precede, accompany and / or severely worsen the disease process, and increase the likelihood of recurrence [14].

Thus, the therapeutic strategy to normalize sleep patterns in patients with depression, can be seen not only as a symptomatic, but rather as a pathogenetic therapy. In this respect, mirtazapine is one of the few antidepressants with proven efficacy against correction insomnicheskih disorders in patients with depression [16].

Another current area of ​​application of mirtazapine may be mentioned geriatric practice. This drug is one of the best in terms of both efficacy and tolerability in elderly and senile age [20, 28]. Given that such symptoms of depression, as concomitant anxiety, sleep disorders, anhedonia, and other particular part of the name in old age, as well as the fact that TCA drugs are not recommended for use in this age group [1], mirtazapine should be considered as the drug of choice in age psychiatry for the treatment of all forms of depressive disorders.

Finally, a kind and very valuable feature of mirtazapine is the possibility of correction with the help of sexual dysfunction (decreased libido, anorgasmia, rapid ejaculation, etc.), Which, on the one hand, are often one of the associated clinical manifestations of depression, on the other ; often develop as a complication of treatment with SSRIs drugs [7, 11]. The ability to safely switch therapy with SSRI drugs to mirtazapine, and proved the effectiveness of the combination therapy (SSRI + mirtazapine) [30] can, in some cases, not only to improve the effectiveness of treatment, but also prevent the development of sexual dysfunction ; One of the most frequent reasons for not continuing SSRI.

Mirtazapine is one of the safest drugs of antidepressants. In contrast to the TAD, it is devoid of cardiotoxicity has no ability to cause serotonin syndrome, exhibits marginally anticholinergic properties (dry mouth, indigestion). The drug can sometimes cause early treatment increased sedation, dizziness, drowsiness, which, however, rarely reach the clinically significant severity and usually take place in the course of further treatment. More significant side effect of mirtazapine is considered increased appetite and weight gain, which, however, are also frequently observed at the beginning of treatment, and only in some cases can cause discontinuation of the drug [15, 25].

Mirtazapine in direct comparative studies was significantly safer antidepressant than amitriptyline, and in comparison with the SSRI drugs rarely cause gastro – intestinal disturbances. Also, mirtazapine has a beneficial effect on the sexual sphere [23, 25].

Thus, for example, mirtazapine can be seen in the new generation of antidepressant efficacy dual receptor mechanism of action (NaSSA) [3, 22, 32]. The possibility of using drugs, combining its mechanism of action effects on various neurotransmitter systems and the high selectivity of this effect, allows:

1) expand the possibilities of pharmacotherapy in different clinical forms of depressive disorders;

2) to ensure the earliest possible manifestation of clinical effect;

3) to carry out an effective and safe therapy for depressive disorders in different age groups;

4) significantly reduce the resistance indices in the treatment with antidepressants.

It was also proved more cost-effective treatment of mirtazapine compared with amitriptyline and fluoxetine at a total assessment of the direct and indirect costs [10].

From the preparations of mirtazapine in the domestic pharmaceutical market sludet note the appearance of the drug Mirtazapine hexane (Germany), which combines a high level of quality in accordance with European standards and affordability. Mirtazapine hexane comes in tablet form for 15, 30 and 45 mg, which can effectively combine different dosage regimens and schemes and carry out the titration of the dose depending on the clinical features, treatment and tolerability of concomitant drug therapy in individual patients.

Further expansion experience with mirtazapine may help to optimize the pharmacotherapy of depressive disorders and improving the strategy and tactics of the new generation of antidepressants.

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