The problem of mental disorders in the elderly and senile age is one of the most important sections of modern gerontology and psychiatry, which formed a separate research direction – gerontopsychiatry. However, in this area, the focus is on senile dementia and other forms of involutional psychosis, affective disorders, and much less on the clinical and therapy features of schizophrenia.
Epidemiology and clinical features
Today in US, schizophrenia is 1.7% of the incidence of elderly and old people . About 10 15% of patients with schizophrenia pathology manifest uet after the age of 60 years. It is important to emphasize that in old age both a certain syndromological dynamics in patients with the onset of the disease at a younger age are revealed , as well as features of the clinical picture of schizophrenia in later age, namely: complication of productive symptoms due to the expansion and deepening of hallucinatory delusions, paranoia Destroy PTS straight and absence of growth deficitsymptoms and even shenii Decrease the manifestations of autism. Attention is drawn to the frequency of the relationship of schizophrenia with senile dementia. It is the development of concomitant senile dementia that contributes to the further development of the mentioned clinical manifestations in the elderly.
Dementia modifies the course of the schizophrenic process in two opposite directions – smoothing out specific personality changes, simultaneously aggravating and weighing down productive psychopathology disorders . In cases of schizophrenia combination with senile dementia age recesses Destroy productive endogenous PTS etc. Practical coincides with the manifestation of dementia. In addition, schizophrenia in old age is characterized by increased and prolonged exacerbations, a decrease in the quality of remissions, a transition to a chronic course, greater acuity and worse compensation for paranoid and paranoid manifestations .
From the point of view of pharmacotherapy, schizophrenia in old age is also characterized by a number of features. The most important of these is the increase in resistance to preparations of conventional neuroleptics and the incidence of their side effects. Especially often in gerontopsychiatry, extrapyramidal disorders and cardiotoxic reactions are observed with the use of phenothiazine and butyrophenone derivatives, which is associated with the age-related weakening of dopaminergic processes, primarily in the nigrostriatal system, impaired conduction and metabolism in the myocardium, as well as slowing down the biotranslation patterns and aspirant patterns. in an aging body.
As a result, the development of neuroleptics, which are not inferior in effectiveness to conventional means, but surpass them in breadth of therapeutic action and safety criteria, has become one of the most important tasks of the development of psychopharmacology. The emerging drugs of the new generation have received the general name of atypical antipsychotics, which currently include clozapine, olanzapine, risperidone, quetiapine, ziprasidone, amisulpride, aripiprazole, and some others.
The specific antipsychotic activity of atypical antipsychotics is generally comparable to that of traditional antipsychotics and is associated with the general mechanism of action of drugs in this group – the blockade of dopamine D2 receptors. type At the same time, the selective tropicity of theaction of atypical antipsychotics on the mesolimbic and mesocortical dopaminergic systems of the brain, as well as a much less pronounced effect on the nigrostriatal system, which is directly related to a significantly more favorable safety profile.
As a result, atypical antipsychotics optimally meet the following criteria for the effectiveness of antipsychotic therapy in geriatric practice, which implies:
- antipsychotic action, comparable in its severity with the classical representatives;
- effects on negative symptoms;
- effects on cognitive symptoms;
- effects on affective symptoms;
- effectiveness in many cases of resistance to conventional neuroleptics.
Finally, it is the assessment of the safety of pharmacotherapy with these drugs, based on the knowledge of the characteristics of the development of certain side effects, that becomes the decisive factor in choosing an instrument of treatment with neuroleptics in a particular patient in old age. As a result, the question arises about the criteria for choosing one or another atypical in gerontopsychiatry.
Each of the atypical antipsychotics is characterized by a peculiarity of the mechanisms of action, clinical effects, and finally, significant differences in the safety profile and, accordingly, differences in the therapeutic spectrum, which determines the feasibility of administering a particular drug in certain clinical forms and syndromes.
One of the most peculiar atypical antipsychotics is quetiapine . It is quetiapine that is considered today by many authors as one of the optimal antipsychotics for treating older patients of their age groups , which is largely due to its original, very own figurative mechanism of action.
Mechanisms of action of quetiapine
Quetiapine blocks D2 receptors type only in mesolimbic and mesocortical dopaminergic systems in the central nervous system, having a very low resistance to D2 nigrostriatal and hypothalamic receptors pituitary ary systems. According to modern ideas, D2 blockade mesolimbic andmesocortical receptors are directly associated with manifestations of the antipsychotic effect, and interaction with D2 receptors in the substantia nigra and striatum are associated with the development of extrapyramidal complications – syndrome of drug parkinsonism and late dyskinesias .Thus, it becomes clear one of the most important clinical benefits of quetiapine – the presence of a pronounced antipsychotic effect in combination with a minimal risk of neurological motor disorders.
Quetiapine is also quite intensively bound to serotonin 5 NT2A by receptors. It is known that serotonin receptors of this type are widely represented in the frontal cortex and various parts of the brain, and that the serotonergic system after 5 NT2A receptors have a modulating effect ondopaminergic structures. According to modern concepts, the serotonergic system plays a key role in the pathogenesis of schizophrenia, in particular, its disorders are directly related to the development of negative symptoms, affective disorders, and secondary cognitive deficits.
Finally, the weakening of serotonergic processes and the imbalance between individual subtypes 5 NT2 receptors – one of the leading mechanisms of brain aging and development in zrastzavisimoy CNS pathology. Therefore, the serotonergic mechanisms of quetiapine action are of particular interest from the point of view of its use in gerontopsychiatry.
It is also important to emphasize the absence of any either quetiapine interactions with postsynaptic M cholinoreceptors, which is one of the most important clinical benefits of this drug – the almost complete lack of risk of extrapyramidal adverse reactions (acute dystonia, akathisia, catalepsy, tardive dyskinesia, drug parkinsonism) – the leading side effect of conventional antipsychotics.
In general, it seems today that the basis of the pharmacological effects of this drug is not so much blockade of certain receptors per se (in its neurochemical sense), but rather a modulating action aimed at normalizing the imbalance of activity of both individual neurotransmitter systems and within the same system (dopamine and serotonergic ), mediated by different receptor subtypes. At the same time, it is this imbalance that serves as the foundation for aging of the brain and disorders of the integrative function of the central nervous system. Quetiapine, like no other atypic, has a normalizing effect on the imbalance mentioned, that is, to a certain extent one can speak of the presence of geroprotective (in their psychiatric understanding) properties of this drug.
In clinical practice, equal efficacy of quetiapine and conventional neuroleptics ( haloperidol , chlorpromazine , fluphenazine , etc.) was demonstrated in reducing positive clinical symptoms based on analysis of various clinical scales (short psychiatric rating scale, scale of overall clinical impression, assessment scale of negative symptoms, etc. ) both during the acute as well as stabilizing and n rotivoretsidivnoy therapy. At the same time, the most important aspect of quetiapine action , in contrast to classic drugs, is the beneficial effect on negative symptoms.
In gerontopsychiatry, an effective effect on hallucinatory delusional symptomatology expressed Decrease the shenie paranoid symptoms.
The beneficial effects of quetiapine on cognitive functions, such as attention, performing functions, and verbal memory, deserve special attention . The severity of cognitive deficit in schizophrenia in old age is considered as the most important indicator in assessing the social and therapeuticprognosis of the disease.
Finally, quetiapine demonstrated the possibility of correcting affective symptoms (depression) in schizophrenic patients by positively affecting the entire cluster of affective disorders, according to a short psychiatric rating scale. Given the importance of the problem of depression in geriatrics, as well as the poor efficacy in stopping these symptoms of traditional antipsychotics and antidepressants, this property of quetiapine deserves special attention.
Quetiapine Safety Profile
Quetiapine optimally meets the criteria for selecting an atypical neuroleptic for geriatric practice in terms of effectiveness, breadth and variety of clinical pharmacological action. However, the main advantage of Quetiapine, which ensured its wide popularity in the world psychiatric practice and, in particular, in gerontopsychiatry, is safety. It is by this criterion that it significantly exceeds not only conventional, but also the majority of atypical neuroleptics .
As already mentioned, due to the lack of affinity for M brain cholinergic receptors, as well as a slight affinity for D to the receptors in the nigrostriatal system, quetiapine is practically devoid of extrapyramidal side effects – the most important negative effect of the use of antipsychotics.
In this respect, the safety of quetiapine significantly higher than traditional drugs, and that kzhe risperidone and olanzapine, is important to emphasize that this characteristic of quetiapine is celebrated all over the therapeutic dose range (100 – 800 mg/day), that is, with increasing doses, as well as with long courses of use, the risk of developing extrapyramidal complications (including tardive dyskinesia) remains minimal.
As you know, serious problems associated with the use of both classical and atypical neuroleptics are the development of hyperprolactinemia (due to the effect on D receptors in the hypothalamo pituitary system) and related sexual dysfunction (including gynecomastia, galactorrhea), as well as the formation of osteoporosis, disorders of water salt metabolism, etc. Many atypical neuroleptics (risperidone, olanzapine, amisulpride) to some extent cause hyperprolactinemia, which in some cases can become a serious clinical problem and lead to the replacement of the drug.Quetiapine is almost completely devoid of the ability to cause these disorders, which significantly increases the safety of its use.
Finally, quetiapine has minimal risk (unlike traditional drugs and olanzapine) for developing metabolic disorders, such as weight gain and diabetes.
The most common side effects of quetiapine are sedation, somnolence, orthostatic hypotension, dizziness, dyspepsia, that is quite soft manifestations are typically dealt with decreasing dose. The likelihood of complications such as malignant neuroleptic syndrome and leukopenia is very low and does not differ in this respect from that of other atypical antipsychotics. Quetiapine, unlike clozapine, does not cause agranulocytosis.
In general, quetiapine can be characterized as one of the atypical antipsychotics most favorable in terms of safety. In combination with the characteristics of the clinical spectrum of action and pharmacokinetics, this allows recommending it as the drug of choice in elderly and senile patients, with a combination of psychotic disorders with dementia and Parkinson’s disease .
Quetiapine preparations Seroquel deserves special attention in the pharmaceutical market in the form of tablets of 25, 100 and 200 mg, which allows you to fully meet the needs for individualization of the dose regimen in different categories of patients depending on the clinical form of the pathology, severity of the condition, age, presence of concomitant diseases, features of combined pharmacotherapy, etc.
Seroquel It is produced in full compliance with all GMP requirements and European quality criteria and, at the same time, it is the most economically available drug Quetiapine , which significantly expands its prospects in domestic clinical practice and is a significant advantage over foreign counterparts.
In general, quetiapine is a promising atypical neuroleptic that deserves widespread introduction into domestic clinical practice. Further accumulation of experience in its use will allow optimizing the pharmacotherapy of schizophrenia in old age in accordance with modern international standards.