LB Lazebnik, Yu.V. Koniev, V.N.Drozdov, L.I.Fremov
Department of Gerontology and Geriatria of the Moscow State Medical and Dental University; Organizational and methodological department for therapy of the Department of Health of Moscow; Central Research Institute of Gastroenterology

Polypragmasia [from "Poly" - many and "Pragma" - the subject, a thing; Synonym - polyterapia, excess treatment, polyfarmatia, "Polypharmacy" (eng.)] - The redundancy of medical prescriptions was and remains a very widespread and poorly-friendly problem in modern clinical medicine.

The most famous drug or drug polyprodia (polyfarmatia, polypharmacotherapy) is the simultaneous purpose of several drugs in elderly patients. The "massive drug strike" (the term of the author), as a rule, receives the most vulnerable contingent of patients, i.e. People suffering from polymorbidity are simultaneously occurring several diseases in various phases and stages. Most often it is older patients.

The number of diseases per patient geryatrical hospital is represented in Fig. one.

Attention is noted that with increasing age, the index "Number of diseases / one patient" decreases. This happens because of several reasons. First, before the old years, people suffering from fewer chronic diseases live. Secondly, it is known that some chronic diseases with age are involved in involutions or disappear (for example, a duodenal ulcer disease). Thirdly, under the influence of treatment, many diseases acquire a different clinical form ("medicinal" or "yathedral polymorphosis"). Examples include the transformation of the painful form of coronary heart disease in non-peculiar agents or the disappearance of angina attacks and normalization with many years of treatment with antiagonal agents arterial pressure After implanting the electrocardiographer.

It is a polymorbonity that generates a patient to be observed simultaneously with the doctors of several specialties, is the cause of drug polypharmacotherapy as a current practice, as each of the observing patients of specialists in accordance with standards or established practice is obliged to perform targets.

In fig. 2 shows the profiles of doctors, at the same time observing an outpatient patient of old age in one of the Moscow polyclinics.

Our many years of experience in the clinical aspertal assessment of the quality of medical diagnostic aid shows that in most cases the principle that the attending physician is guided by a patient at the same time several drugs reflects his desire to cure all the disease available in a patient (preferably, peristers), and at the same time to prevent All possible plants (preferably reading).

The doctor who is guided by these good intentions appoints the drugs known to him by the usual schemes (sometimes "from pressure", "from constipation", "from weakness", etc.), at the same time thoughtlessly combining in general correct recommendations of numerous consultants who believe that It has already been indicated above, mandatory introducing additional treatment in its profile.

As an example, we present simultaneous administration to the disabled person of the Great Patriotic War (we are talking about the dosage system for the DLO system) 27 of different drugs in the amount of more than 50 tablets per day, and the patient not only insisted on their receipt, but it all took! The patient suffered from twelve diseases and was observed in eight specialists (therapist, cardiologist, a gastroenterologist, a neurologist, an endocrinologist, a urologist, an oculist and a otorinolaryngologist), each of whom appointed "his" treatment, not even trying to relate him to the recommendations of other specialists. Anxiety raised, naturally, therapist. Believe me, huge work was worth convincing the patient to abandon the reception of a huge amount of drugs. The main argument for him was the need to "regret the liver."

The problem of polypharmacotherapy has long arose.

Being the head of the pharmacology of the Military Medical Academy in 1890-1896, I.P. Pavlov once wrote: "... when I see a recipe containing three or more medicines, I think: what dark power is imprisoned in it!" It is noteworthy that the prescribed by I.P.Pavlov in the same period of the medicine called by him, contained only two drugs (sodium bromide and caffeine), operating in force in the functional state of the central nervous system.

Another Nobel laureate, a German doctor, bacteriologist and biochemist Paul Erlich dreamed of creating a medicine that would be one, like a "magic bullet", killed all diseases in the body, without causing him the slightest harm.

According to I.P. Pavlov, polypragmazia should be considered the simultaneous purpose of the patient of three or more drugs, and according to P. Erlyha, more than one.

The causes of medicinal polypharmacotherapy, both objective and subjective, several.

The first objective reason is, as we have already indicated, the old polymorbidity ("redundancy of pathology"). The second objective cause in geriatration is the absence, weakening or inverting of the expected finite effect of the drug due to changes in drug metabolism in a fading body with naturally developing changes - the weakening of metabolic processes in the liver and tissues (including cytochrome activity P450), decrease in circulating blood volume, reduction of renal clearance, etc.

Getting an insufficient or perverted effect from prescribed drugs, the doctor changes the treatment most often towards an increase in the number of tablets or replace the drug to "stronger". As a result, heroic pathology is developing, named earlier "drug disease". Now such a term does not exist: they say "unwanted" or "side" effects of drugs, hiding behind the terms inability or unwillingness to see the systemality of the active substance on the human body as a whole.

The attentive analysis of the gradual development of numerous diseases in the elderly allows the syndromes that characterize the systemic effects of drugs in the body of an old man - a psychogenic, cardiogenic, burglar, digestive, enterogenic, hepatogenic, from, etc.

These syndromes caused by a long-term exposure to the organism, clinically look and are regarded by a doctor as a disease PER SE or as a manifestation of natural aging. We believe that thinking about the essence of things the doctor should pay attention to the accelerated pace of development of the newly fixed syndrome and try to at least chronologically associated it with the time of the beginning of the reception of this drug. It is the pace of development "Disease" and this relationship can tell the doctor the true genesis of the syndrome, although the task is not easy.

These final systemic effects, developing during long-term, often many years of drug use by the elderly, are almost always perceived by the doctor as a manifestation of the organism aging or the accession of a new disease and always entail an additional appointment of drugs aimed at the cure of the "newly detected disease".

Thus, the long-term reception of spasmolitics or some antihypertensive drugs can lead to atonic constipation, followed by long-term and unsuccessful, most often with laxatives, then to the intestinal diverticulosis, diverticulitis, etc. At the same time, the doctor does not assume that the constipation changed the intestinal flora, the extent of hypeRendotoxinemia increased, aggravating heart failure. Doctor's tactics - strengthen the treatment of heart failure. The forecast is clear. Dozens of such examples can be given.

The simultaneous reception of prepasses leads to drug interactions in 6% of patients, 5 is engaged in frequency up to 50%, when taking 10 prepaids, the risk of drug interactions reaches 100%.

In the United States, up to 8.8 million patients are hospitalized annually, of which 100-200 thousand die due to the development of adverse adverse reactions associated with the use of drugs.

The average number of prepasses taken by the elderly patients (both the dots and those accepted independently) were 10.5, while at 96% of cases doctors did not know exactly what their patients take.

In fig. 3 shows the average daily amount of drugs taken by patients of the geriatric hospital (according to our employee O.M.Mikhev).

Physically more active people took less medication, and with an increase in the age, the number of drugs consumed decreased, which confirms the well-known truth: less people live longer people.

From the objective causes of drug polyfarmakotherapy, subjective - yatrogenic, caused by the appointments of the medical worker, and dischargen, due to the actions of the treatment of the patient.

At the heart of the henogenic causes, it is primarily a model of therapeutic and diagnostic tactics - the treatment must be complex, pathogenetic (with the impact on the main stars of pathogenesis), and the examination is the most complete. These in principle are completely the right foundations are laid in the program of idle training of the doctor, programs and postgraduate education.

Teaching the interaction of drugs cannot be recognized as sufficient, the relationship between drugs, food additives and food intake, doctors are extremely weak. Often, the doctor makes a decision on the appointment of a drug, while under the suggestive impact of the recently obtained information on the wonderful properties of the next pharmaceutical novelty, confirmed by the "unique" results of the next multicenter study. However, for promotional purposes, it is silent that patients were included in such a study on rigid criteria, excluding, as a rule, complicated by the current disease or the presence of other "related" diseases.

Unfortunately, it is necessary to state that the problems of compatibility of drugs in vivo, and the issues of many years of use of this drug or drugs of this pharmacological group are not affected by the problem of pre-and postplomal formation. The possibilities of self-education of the doctor in this area are limited. Not everyone is available to the compatibility tables of two drugs, and as for three or more, it seems that modern clinical pharmacology has not yet come to find a response to this vital issue.

At the same time, it should be noted that we ourselves can make an idea about it only on the basis of a long experience. Reasonable arguments based on many years of observation made it possible to abandon recommendations on the life-long use of estrogen replacement therapy; Carefully refer to recommendations on the life-long use of proton pump inhibitors, etc.

Volens Nolens, even a highly educated thinking doctor, starting to treat a patient with polymorbidity, each time is forced to work in the cybernetic system of "black box", i.e. Situations where the decision makes it knows that it introduces to the system and that it should receive at the exit, but has no idea of \u200b\u200bintrastable processes.

The main cause of polypharmacotherapy on the part of the patient is discominatedness in relation to medical purposes.

According to our studies, up to 30% of patients did not understand the explanations of the doctor relating to the titles, the treatment regimen and treatment tasks, and therefore were engaged in self-medication. About 30%, listening to the doctor and agree with him, independently refuse to treatment on financial or other considerations and change it, preferring to complement the recommended treatment or habitual (in essence ineffective) drugs or means, to use which they advised familiar, neighbors, relatives or Other medical (including ambulance) workers.

A significant role in the perversion of treatment is also played by aggressive advertising of food additives, which are presented by the media as "a unique tool ..." ("Order Urgently, the stock is limited ..."). The effect of uniqueness is enhanced by reference to the mysterious Ancient, African or Kremlin origin. The "warranty" effect is sometimes laid in the name of the goods or the hypocritical recommendation to consult a doctor who, even with a great desire, will not find any objective information about this miracle. References to the popularity of "ancient means from" in the claimed country producer are insolvent: questions specified in this country about this "means" cause bewilderment from the local population.

In my practice, we appeal to common sense: we advise our patients not to believe advertising emanating from the media about these wonderful means, we convince them that the real effective effectiveness of the drug manufacturer would first of all inform the professional community, and not on radio or television.

Considering everything outlined, it is impossible to not welcome the creation of the headed ChL-Cor. Ramna prof. V.K. Lespakhin Federal Center for Monitoring the Safety of Drugs Roszdravnadzor.

Our many years of experience allows our vision of pharmacotherapy options for polymorbidity (Fig. 4).

We allocate rational and non-rational options for pharmacotherapy during polymorbidity. The condition for successful use and achievement of the goal with a rational version is the competence of a doctor and a patient. In this case, the effect is achieved when using sound technology, when, due to clinical need and, with pharmacological safety, several drugs or forms are prescribed a patient simultaneously.

If there are several diseases, it is necessary to prescribe drugs with a proven lack of mutual influence. To achieve a larger effect in the treatment of one disease, for the purpose of the potentiation of one effect, preparations of unidirectional action are prescribed in the form of several dosage forms of different items or in the form of ready-made medicinal forms of factory production (for example, an angiotensin-enzyme enzyme inhibitor and a diuretic in one tablet - "Polypills" in the form of Tablets of several differences in the chemical composition of drugs, but sealed in one blister, and even with an indication of the reception time, etc.).

Another option for rational pharmacotherapy during polymorbidity is the principle of multi-purpose monotherapy, i.e. Simultaneous achievement therapeutic goal In the presence of the system effect of this medicinal preparation.

Thus, entering European and national recommendations to the appointment of the α -adrenoblocker doxazozin, male suffering from the arterial hypertension and prostate hyperplasia, were developed in detail by our employee E.A. Climanova, which also showed that in the appointment of this drug there is a correction of light forms of insulin resistance and hyperglycemia. Other Other employee M.I. Kadskaya first showed the systemic nonanotechnical effects of statins, named later than Pleiotropic.

We believe that it is Multi-Purpose Monofarmacotherapy that will largely allow to avoid those irrational options for pharmacotherapy during polymorbidity, which are presented in the right columns of the scheme and which was mentioned above.

Thus, we believe that polypharmacotherapy should be considered the appointment of more than two drugs of different chemical composition for one reception or within 1 day.

Ronated drug polyfarmakotherapy in modern clinical practice, provided its safety and appropriateness, not only possible, but in difficult and difficult situations it is necessary.

Unreasonable, incompatible, simultaneous or for 1 day, a prescribed large amount of drugs, one patient should be considered irrational polypharmacherapy or "medicinal polyprodium".

It is appropriate to recall the opinion of the famous therapist I. Madyar (1987), which, based on the principle of the unity of the medical and diagnostic process, proposed to more widely interpret the concept of "polypragmasia". He believes that polypragmasia diagnostic (excessive actions of the doctor, aimed at the diagnosis of diseases, including the use of super-modern, and therapeutic polypragmasia, and provoking each other, are considered countless and provoking Non-generation. Both types of polypragmasia are generated, as a rule, "undisciplined medical thinking."

It seems to us that this very difficult issue requires special study and discussion.

On the one hand, it is impossible not to recognize that many doctors, especially young, weakly possessing clinical diagnostics, not interchangeability and complementarity of different diagnostic methods prefer to assign "additional" surveys ("instrumentalism" from ignorance!), Having to conclusion, not even bother familiarize yourself with him. In addition, a rare doctor in modern practice accompanies the patient during diagnostic manipulations, is limited to a finished conclusion and does not delve into the structure of the original indicators.

The huge loading of laboratories and technical diagnostic services is due to the approved standards and diagnostic schemes, which are not always taking into account the logistical and economic possibilities of this LPU.

The diagnostic component of the value of the treatment-diagnostic process is steadily increasing, the financial needs of modern health care does not withstand the economy even highly developed countries.

On the other hand, any doctor will easily prove that the "additional" diagnostic examination appointed by him was extremely necessary as having a targeted purpose and in principle will be right.

Each doctor can lead no one example when a severe or prognostically unfavorable disease was found when conducting a random ("just in case"!) Diagnostic manipulation. Each of us is a supporter of the early and constantly conducted oncopoeia.

Modern diagnostic systems are practically safe for health, manipulation used in their conduct, easily tolerate, so that the concept of "benefit harm" becomes conditional.

Apparently, speaking of the modern aspects of the "diagnostic polypragmasia" it is necessary to keep in mind the rationale for the "purpose value".

We deliberately use the concept of "goal", replaced in some guidelines for pharmacoeconomics by the term "expediency". The economic "expediency" of some non-key politics-economists to key roles easily replace the ethical concept of "goal". So, according to some of them, the state support of the medical and diagnostic process is inappropriate, etc.

The goal is the earlier detection of chronic disease. Thus, it suggests itself to the conclusion about the need for a multiple a detailed medical examination throughout the human life, i.e. Dispensarization implying mandatory results with laboratory, endoscopic and radiation technologies.

Based on the Moscow experience, we believe that this option for the development of health care is possible.

We offer our rubricification of different variants of polypragmain (Fig. 5).

We believe that to prevent unfounded diagnostic and therapeutic polypragmasia in people of the older age groups, the doctor must adhere to the following principles.

1. The survey risk should be less than the risk of unidentified disease.
2. Returning must be appointed primarily to confirm, but not to deviate the preliminary diagnosis, which must be justified.
3. Follow the rule formulated by the famous therapist and clinical pharmacologist by B.E.Votchalov: "Smaller medicines: Only what is absolutely necessary." The lack of direct testimony to the prescription of the drug has contraindications.
4. Adhere to the "Low Dose" regime in relation to almost all drugs, with the exception of antibacterial ("only dose makes the medicine poison"; however, rightly and the opposite: "Only a dose makes poison medicine").
5. Properly choose the ways of removing drugs from the organism of an elderly person, giving preference to drugs with two or more ways of removal.
6. Each appointment of a new drug must be carefully suspended taking into account the features of the drug (pharmacokinetics and pharmacodynamics) and so-called side effects. Note that they should be familiar with the patient himself. Prescribing a new medicine, you need to think if you should cancel some kind of "old".

The presence of the elderly patient of multiple pathology, mosaic and erase of clinical manifestations, complex and fancy plexus of complaints, symptoms and syndromes caused by clinical manifestations of aging processes, chronic diseases and medicinal effects (Fig. 6), make treatment with a creative process, at which the best solution is possible Only due to the thinking of the doctor.

Unfortunately, modern specialists, especially narrow, began to forget the long-term rule developed by a simple rule, allowing to avoid medicinal polyprograms: the patient (of course, except for the urgent situations) should not receive more than 4 drugs at the same time, and the issues of increasing treatment should be solved by several specialists (consilium) . With a joint discussion, it is easier to predict possible drug interaction, the reaction of a holistic organism.

In the treatment of each particular patient, according to the old commandments: "EST modus in rebus" (observing the measure) and "non nocere" (not harmable).

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5, Razuvanova E.M. 5, Makeev D.G. 5, Askherova A.A. five
1 FGBOU in RNIMU them. N.I. Pirogov Ministry of Health of Russia, Moscow
2 OSP FGBOU WITH "RNIME them. N.I. Pirogov "Ministry of Health of Russia" RGNCC ", Moscow; FGAOU in "Russian University of Friendship Peoples", Moscow
3 OSP FGBOU in "Rhinim them. N.I. Pirogov "Ministry of Health of Russia" RGNCC ", Moscow; FGBOU in "Rhinim them. N.I. Pirogov "Ministry of Health of Russia, Moscow
4 OSP Russian gerontological scientific-Clinical Center - FGBOU in RNIMU them. N.I. Pirogov Ministry of Health of Russia, Moscow, Russia
5 FGAOU in "Russian University of Friendship Peoples", Moscow

The population of the Earth agrees, and this process is largely due to achievements in pharmacology. The appointment of modern drugs (LS) Elderly people contributes to the extension of their lives, prevents the development of certain diseases and complications, but the use of an excessive amount of LANs by older people may cause unwanted reactions, including serious and fatal outcome. At the same time, since patients are aging and become fragile, the focus of pharmacotherapy shifts towards controlling the symptoms of diseases, improving the quality of life and minimizing the use of potentially dangerous preventive LS, which will bring a little benefit for a relatively short life expectancy.
To reduce the risk of negative consequences of polypragmasia in elderly patients, a number of approaches can be recommended, including educational activities, auxiliary computer systems, as well as modern methods presented in this article: Anticholinergic load scales, STOPP / START criteria, Birca criteria, application rationality index drugs, comorbidity indices. Application during the drug audit of these tools allows you to reduce the drug load and improve the safety of pharmacotherapy.

Keywords: Elderly, safety, polypragmasia.

Citation:Tkacheva O.N., Pereverzev A.P., Tkacheva, Kotovskaya Yu.V., Shevchenko D.A., Apresyan V.S., Filippova A.V., Danilova M.G., Reluvanova EM, Makeev D.G., Askerova A.A. Optimization of drugs in patients of elderly and senile age: Is it possible to beat polypragmazia? // RMW. 2017. №25. P. 1826-1828

Optimization of Medicinal Presscriptions in Patients of Elderly and Senile Age: Is it Possible to Defeat Polypharmacy?
TKACHEVA O.N. 1, Pereverzev A.P. 1,2, Runikhina N.K. 1, Kotovskaya Yu.V. 1,2, SHEVCHENKO D.A. 2, APRESYAN V.S. 2, Filippova A.V. 2, Danilova M.G. 2,
Razuvanova E.M. 2, Makeev D.g. 2, ASKEROVA A.A. 2.

1 Russian Gerontological Scientific and Clinical Center, Moscow
2 Peoples "Friendship University Of Russia, Moscow

The Population of the Earth Is Aging, And this Process IS Largely Due to Advances in Pharmacology. The appointment of modern medicines to elderly people contributes to the prolongation of their life, prevents the development of certain diseases and complications, but the use of excessive amounts of drugs by elderly people can lead to adverse drug events, including serious and fatal ones. At the same time, as the patients become older and frailer, the emphasis of pharmacotherapy shifts towards controlling the symptoms of diseases, improving the quality of life and minimizing the use of potentially dangerous preventive drugs that will benefit little over a relatively short expected life expectancy . To reduce the risk of negative consequences of polypharmacy in elderly patients, a number of approaches can be recommended that include educational activities, ancillary computer systems, and modern methods presented by the authors in this article: anticholinergic load scales, STOPP / START criteria, Bierce Criteria, Index of Rational Drugs Administration, COMORBIDITY INDICES. The Use of these Tools During The Drug Audit Can Reduce The Drug Load and Improve The Safety of Pharmacotherapy.

Key Words: Elderly, Safety, Polypharmacy.
For citation: TKACHEVA O.N., PEREVERZEV A.P., RUNIKHINA N.K. et al. Optimization of Medicinal Presscriptions in Patients of Elderly and Senile Age: Is it Possible to Defeat Polypharmacy? // RMJ. 2017. No. 25. P. 1826-1828.

The article is devoted to the issues of optimization of drugs in patients of elderly and senile age. To reduce the risk of negative consequences of polypragmasia in elderly patients, a number of approaches can be recommended that include educational activities, auxiliary computer systems, as well as other modern methods presented in the article.

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Department of Psychiatry and Narcology, Federal State Budgetary Educational Institution of Higher Education "St. Petersburg State University"

SUMMARY: The article discusses the problem of applying antipsychotics combinations. To date, the gap between the results of evidence-based medicine and the real daily practice of a combination therapy physician is quite large with antipsychotics. Based on the literature data presents an overview of the causes and negative effects of antipsychotic polypragmasia, as well as the clinical situations in which it is justified. Research results allow us to recommend combined antipsychotic therapy to patients who did not help at least three courses of monotherapy with antipsychotics, including clozapine; It is possible to argue antipsychotic therapy with drugs of other classes; With the inevitability of antipsychotic polypragmazy, take into account the doses of drugs (risperidone and chlorpromazine equivalents). It should be emphasized that most patients passing a course of combined antipsychotic therapy are able to safely switch to monotherapy with an antipsychotics, thereby reducing the costs of treatment and raising compliance.

Combined therapy of psychotic disorders at various stages of treatment can be at least three species: a combination of antipsychotic drugs and psychotherapeutic rehabilitation techniques; Potentation method - a combination of antipsychotics and other types of psychotropic drugs - antidepressants, mood stabilizers and tranquilizers; Combination of two or more antipsychotic drugs. A feature of the current stage of psychopharmacotherapy is the mass polypragmasia, i.e., the widespread use of various combinations of psychotropic drugs. Up to 80-90% of patients both in the hospital and outpatients are one or more psychotropic drugs.

Clinical recommendations on the optimal use of psychotropic drugs are wide available, but their appointment in real-day practices is usually different from the proposed algorithms. Polyprigmas, the use of high doses of antipsychotic drugs, as well as supporting treatment with benzodiazepines or anticholinergic substances, do not have a reliable evidence base and may cause serious adverse effects.

Under antipsychotic polypragmazy, the combined appointment of two or more antipsychotic drugs is understood. Opinions on the temporary criteria for the establishment of polypragmasia are diverged: Some authors considered polypragmazy combined therapy for 14 days, others - 60 or 90 days. E. Leckman-Westin and co-authors (2014) expressed the view that the most appropriate, expedient measure is the period of more than 90 days with a possible interruption of 32 days, since it is this period that is characterized by a sensitivity of 79.4% and a specificity of 99.1%. Brief episodes of intake of antipsychotics combinations may be present when changing therapy, the transition from one drug to another, which corresponds to modern treatment strategies.

Antipsychotic polypragmasia continues to be a common phenomenon in both domestic and foreign clinical practice. The prevalence of polypragmain of antipsychotics, according to different studies, ranges from 7 to 50%, and in most sources ranges from 10 to 30%. Analysis of a significant number of studies with almost 1.5 million participants (82.9% - schizophrenia patients) showed that the average frequency of antipsychotic polypragmain in the world is 19.6%. The most frequently used option for combined therapy is the combination of the first and second generation antipsychotics (42.4%), the second place occupies a combination of two antipsychotics of the first generation (19.6%), after it - the second generation (1.8%). Over the period from the 1970s to 2000s, the average frequency of use of antipsychotic polypragmazia did not significantly change (1970-1979: 28.8%; 1980-1989: 17.6%; 1990-1999: 22.0%; 2000- 2009: 19.2%, p \u003d 0.78). However, there are noticeable differences in the regions: in Asia and Europe, polypragmazia can be found more often than in North America, in Asia - more often than in Oceania. The differences in the prevalence of polypragmazia can be explained by different demographic and clinical characteristics of samples, as well as various studies. The greatest prevalence of antipsychotic polypragmazia is noted in patients of psychiatric hospitals (more than half of the patients). Its appointment correlates using antipsychotics of first generation and proofreaders, the presence of the diagnosis of "schizophrenia", more rarely using antidepressants and more frequent - prolonged forms of antipsychotics.

The results of the survey of domestic psychiatrists made it possible to refute the assumption that the reason for the use of high doses and combinations of antipsychotics, as well as the cause of the development of unsuccessful treatment outcomes, in most cases is only an unfavorable course of the disease and / or relative resistance of some part of patients with antipsychotic monotherapy in moderate doses . According to reports, when building exacerbations, 40% of psychiatrists prefer to use combinations of "classic" antipsychotics. 10% of doctors prefer to add a second antipsychotics into a treatment regimen with insufficient effectiveness of the first, and the vast majority of specialists increase the dose. 7.5% of the surveyed doctors spoke in favor of the preference of use for the prevention of recurrence of the disease combinations of antipsychotics. It turned out that psychiatrists working in male branches, to relieve exacerbations of schizophrenia, prefer to use combinations of two or more antipsychotics (mostly traditional), but practically do not apply monotherapy for these purposes with antipsychotics of the second generation. Probably, such preferences are due to the desire to quickly reduce the disorganization of behavior, impulsiveness and aggressiveness, which are known to be more pronounced in men 'patients. A certain role seems to play a distress arising from psychiatrists when working with the most severe contingent of patients. Most doctors hospital working in the women's departments prefer to use monotherapy with antipsychotics of first generation, although there are supporters of polypragmasia among them. On monotherapy, only psychiatrists operating in the rehabilitation department were chosen. Among psychiatrists with experience of the work of over 10 years, the proportion of polypragmatics reaches a maximum, apparently, due to obsolete stereotypes of treatment.

There is no doubt the insufficient validity of the antipsychotic polypragmazia. Combined therapy is often prescribed without sufficient grounds and the possibility of drug interactions is not accustomed. Thus, approximately the fifth of the outpatient patients with schizophrenia along with prolonged neuroleptics additionally receives traditional neuroleptics or recently atypical antipsychotics inside, which can completely level the positive features of their clinical action.

Evidence of the effectiveness of polypragmazia is found only in small randomized controlled clinical studies, descriptions of clinical cases, and often based on the personal experience of the doctor. There are practically no preclinical studies of antipsychotics combinations, although embodiments of antipsychotic therapy of other classes are studied. Few attention is paid to identifying the antipsychotic potential of compounds, the animals study side effects, but this does not apply to the combined antipsychotic therapy.

There is no uniform opinion on the consequences of antipsychotic polypragmazy at present. Most studies suggest that antipsychotic polypragmation is associated with a number of negative consequences, including risk raising side Effects Compared to monotherapy and an increase in health expenditures.

On the example of the analysis of 575 histories of the disease E.V. Sallakov and K. Badri demonstrated that the use of combinations of antipsychotic drugs is associated with lower quality of remission, which can be due to a number of factors, including greater severity of the mental state, the presence of therapeutic resistance and low compliance of patients. The probability of the development of side effects increases in proportion to the number of prescribed drugs.

The most convincing unwanted consequences of antipsychotic polypragmation are shown for extrapyramidal side effects, accompanied by the use of anticholinergic drugs, to increase the level of prolactin. Both of these side effects can be explained by a greater total dose and blockade of dopamine receptors. Although the reduction of doses of each drug during their combination can contribute to a reduction in side effects, the likelihood of their effects may decrease with a greater probability. The discrepancy of data on the frequency of acactic with antipsychotic polypragmazia testifies in favor of the hypothesis that it is not primarily connected with the dopaminergic system. This is consistent with the frequent lack of effect on the use of anticholinergic drugs, in contrast to beta blockers and benzodiazepines. In addition, antipsychotic polypragmazia is associated with an increase in the risk of metabolic syndrome. In favor of the need to avoid antipsychotic polypragmazia indicate data on the increased risk of such side effects, such as Parkinsonism, hyperprolactinemia, hypersivation, sedation and drowsiness, cognitive disorders, diabetes, and possibly dislipidemia.

It was noted that with the simultaneous purpose of two or more antipsychotics, most doctors do not take into account chlorpromazine equivalents, which becomes the most common cause of irrational therapy, and in the end - the neurotoxic influence of high and ultra-high total doses on integrative (frontal) functions, slowing the recovery processes, deterioration of remission , development of mental and somatoneurological side effects.

At the same time, the effect of the cohort cannot be eliminated: the moral and psychological orientation of the individual on the standard of behavior, characteristic of the public group to which it relates (it means lifestyle, non-compliance with diet and smoking, lower patient education). Data in terms of weight gain, Qt interval and increase mortality risk are considered ambigurative. There are no convincing data regarding potential addictive properties and such possible negative consequences as late dyskinesia, malignant neuroleptic syndrome, agranulocytosis, sudden heartfelt death, convulsions and increased levels of hepatic enzymes.

It was suggested that polypragmazia is associated with an increased risk of mortality of mentally ill. According to the literature, it reaches twice as much frequencies compared to the overall population and cannot be explained by the increased risk of suicide. Schizophrenia patients are more often sick with cardiovascular diseases and diabetes. This is due to both the style of life, the nature of nutrition, smoking, lower education, and with antipsychotic therapy, causing, for example, the elongation of the Qt interval and the ventricular tachycardia of the type "Pirouette". It is shown that the risk of death from cardiovascular pathology increases with an increase in the dose of antipsychotics, regardless of its generation. However, in patients with schizophrenia that do not receive antipsychotics, mortality is 10 times more than that of passing pharmacotherapy. Long-term effects of polypragmasia from this point of view are not sufficiently studied. There are data on raising the risk of death with an increase in the amount of antipsychotics used.

The study of cognitive deficit has shown that it depends on doses of drugs (risperidone and chlorpromazine equivalents), and not directly from the number of prescribed drugs (dosage more than 5-6 mg of risperidone equivalents were associated with lower BACS results). It is important to note that when combinations of antipsychotic drugs, prescribed doses often exceed the recommended.

Data on the adverse effects of antipsychotic polypragmascus, and they are contradictory. Most studies were either conducted on the basis of analysis of diseases, or are descriptive studies, often with a small sample size and lack of a control group. Some researchers have shown the lack of influence or even improved patient's condition for side effects under therapy with certain combinations of antipsychotics and / or after adding a second antipsychotics or with a decrease in the dose of the first antipsychotics. For example, a combination of two antipsychotics with a decrease in dose initially used by the drug can help normalize the level of glucose in the treatment of clozapine or the level of prolactin and the severity of extrapyramidal disorders associated with therapy with risperidone, while maintaining a sufficient level of blockade of dopamine transmission, and therefore therapeutic efficacy. In many studies, it was reported that the antipsychotics of antipsychotic therapy with an antipsychotics of the second generation by Aripiprazole leads to a decrease in such side effects, such as sedation and drowsiness, hypersivation, an increase in body weight, dyslipidemia, hyperprolactinemia and sexual dysfunction is likely due to its properties of the partial agonist of dopamine receptors of the 2nd Type. It remains unclear how the use of Aripiprazole can help reduce weight and reduce metabolic disorders associated with taking clozapine and olanzapine. Some studies showed a positive effect on the level of glucose addition to the quetiapine treatment scheme when a dose of clozapine is reduced to the level of prolactin and extrapyramidal disorders - combination of ziprasidone or small doses of haloperidol with low doses of risperidone. The study in which risperidone or Ziprasidone was prescribed in combination with clozapine, showed that patients continued to gain weight and significant differences in side effects were not observed. It is not known whether the effect of reducing unwanted phenomena will be observed when appointing antipsychotics with a low risk of side effects when therapy by clozapine or olanzapine therapy without reducing their dose. The results of the meta analysis indicate the positive effect of antipsychotic polypragmation in the case of closapine.

The popularity of polypragmazia is explained by the fact that, unfortunately, a third of patients cannot achieve a complete response to antipsychotic therapy. In the Psychopharmacotherapy Guide, the Exodus Studies Group in patients with schizophrenia in recommendations on aggregation strategies is indicated that many patients have an incomplete response to monotherapy. In these cases, polypragmasia is a component of strategies using clozapine. In clinical practice in 60% of cases, clozapine is appointed not in the form of monotherapy, but in combination with other antipsychotics. Although fundamental scientific studies suggest that the chlorination of clozapine other antipsychotics contributes to greater binding of dopamine receptors, in clinical studies its effectiveness has not been demonstrated sufficiently. Most of the studies are devoted to the combination of clozapine and risperidone. The combination of risperidone with clozapine was studied in randomized placebo-controlled studies. Only in one of them, combined therapy was significantly different in the expression of psychopathological disorders effect. In general, the studies of this combination of drugs did not demonstrate the proper level of efficiency and safety to include it in the recommendation on the treatment of patients with therapeutically resistant schizophrenia. The lack of differences from placebo with the egrenation of clozapine therapy was also shown for amisulpride and Aripiprazole. The recent meta-analyzes of the chlorination of clozapine and the effectiveness of polypragmazia indicate that the benefit from it may be absent or being insignificant. More bases exists for antipsychotics of psychotropic drugs of other classes, such as norms.

As examples of the use of polypragmasia in clinical practice, several schemes discussed in printing on the results of retrospective clinical observations can be brought. So, additional to risperidone or olanzapine is the purpose of thiuridazine in the initial period of therapy made it possible to stop the alarm and the match. In other messages, there was a positive experience of a short-term addition of antipsychotics to relieve atypical manic symptoms that occurred after the assignment of risperidone or olanzapine. In this case, it is impossible to judge whether this effect is a consequence of pharmacological action or this spontaneous phenomena within the dynamics of schizoaffective pathology. It does not discuss the possibility of transition to another atypical antipsychotic drug, adding a mood stabilizer or optimizing the dosage of the original selected tool.

The combination of two and more typical neuroleptics in most cases does not have indications. There is little data that confirm the feasibility of using antipsychotics combinations if monotherapy was effective. Although such strategies for combinations of drugs are widely used in clinical practice, they are outside the focus of the attention of manuals on the diagnosis and treatment of schizophrenia.

The transition from antipsychotic polypracity to monotherapy with antipsychotics was considered in a very limited number of studies. In some of them, 50-67% of patients were safely transferred such a correction of psychopharmakotherapy. Of meaningful differences in the number of hospitalization and severity of symptoms between groups of patients who continued to receive two drugs and transmitted to monotherapy was not. Most of the patients from among those who had a correction correction in the future, after the transition to monotherapy, returned to therapy with the initial combination of drugs. At the same time, it is evidence that in cases of changing the attending physician in patients receiving more than one antipsychotics, the psychiatrists are not inclined to monotherapy.

It should be noted that in domestic standards of schizophrenia therapy there are no recommendations on the number of prescribed drugs, only the recommended doses of antipsychotics are given. There are guidance on the use of combination therapy with clozapine with a different antipsychotics of the second generation (preferably an amisulpride [level of evidence C], risperidone [C], aripiprazole [d]), which may have advantages compared to monotherapy.

According to domestic specialists, in national standards of antipsychotic therapy, certain restrictions should be established concerning the dosing of drugs and the use of polypragmasia; Recommended dose ranges of classical antipsychotics should be revised in the direction of their decrease, and the potentiation of the sedative effect in the necessary cases is preferably achieving combinations of antipsychotic drugs with psychotropic means of other classes (for example, with mood stabilizers and / or anxiolytic).

In general, the results of a systematic analysis of side effects associated with antipsychotic polypragmazy indicate that this area remains not sufficiently studied. In addition, not all combinations of antipsychotic drugs are equivalent. Antipsychotics are used to reduce the psychopathological symptoms and suffering from the patient and, ideally, improving its quality of life and raising the level of social functioning. Since there is no evidence that the effectiveness of antipsychotic polypragmazia exceeds the observed during monotherapy, its use cannot be recommended.

Despite the fact that many organizations and institutions began implementing the policy of preventing the use of antipsychotic polypragmazy, there is little evidence in favor of their prohibition in some cases. There are currently no sufficient data to assess the potential risk, advantages and environmental outcomes related to antipsychotic polypragmazia.

It seems appropriate to recommend combined antipsychotic therapy to patients who did not help at least three courses of monotherapy with antipsychotics, including clozapine. In other cases, the duration of polypragmazia should be based on clinical need: when changing therapy or when overcoming therapeutic resistance. It is important to take into account that most patients passing a course of combined antipsychotic therapy are able to move to monotherapy with an antipsychotics.

Methodical recommendations for eliminating the practice of suboptimal administration of drugs, developed on the basis of Maudsley (2001) guidelines (2001) guidelines indicate that polypragmasia, i.e., the use of two substances of the same class should be avoided, except when cases There is either a database that supports such practice (for example, a combination of mood stabilizers), or evidence of specific benefits for the patient.

Thus, it is possible to state the gap between the results of evidence-based medicine and the real daily practice of the doctor with respect to combined antipsychotics therapy. Most psychiatrists use polypragmazia, however, it should be borne in mind that the sequential switching from one antipsychotic drug on another performance may exceed the combined therapy, and the combined antipsychotics treatment can be one of the ways to overcome therapeutically resistant states. It is preferable to consider the additional purpose of small doses of antipsychotics to the antipsychotics of the second generation for a short period.

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Antipsychotic Polypharmacy: Pros and Cons

Nataliia Petrova, Mariia Dorofeikova

Department of Psychiatry and Narcology, Saintkpetersburg State University, St.kpetersburg, Russia

Summary. This Review Addresses The Problem of Antipsychotic Polypharmacy. Currently There Is A Large Gap Between The Results of Evidence-Based Medicine and Daily Practice of a Doctor Concerning Combined Antipsychotics Use. Based on the literature Review An Overview of the Causes and Negative Consequences of Antipsychotic Polypharmacy is presented, The Cases in Which It is justified. Allow to Recommend a Combined Antipsychotic Medication in Patients Who Have Failed At Least Three Courses of Monotherapy, Including Clozapine; If Possible, to Augment Antipsychotic Therapy With Other Classes of Drugs; When Polypharmacy Is Inevitable, Take Doses (Risperidone and Chlorpromazine Equivalents) Into Account. It is Worth Emphasizing That The Majority of Combined Antipsychotic Medication Can Safely Transfer to Antipsychotic Monotherapy, Thereby Reducing The Cost of Treatment and Increasing Compliance.

Key Words:schizophrenia, Antipsychotics, Polypharmacy.

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Polyprigmas (polyfarmatia) is a widespread problem of modern clinical medicine, which arises due to excessive purpose by specialists of drugs. This phenomenon is more often found in the elderly, who simultaneously suffer from several diseases.

What is the problem?

Polyprigmas - the usual tactic treatment of many pathologies. Therefore, in conditions of the hospital or outpatient care, the patient often gets at the same time from 2 to 10 drugs. In this case, the number of drugs is determined by the severity of the state, the presence of related pathologies, alertness of a specialist and a patient.

Important! The joint use of several drugs can increase the risk of adverse reactions and interaction between medicines, reduce the commitment of patients to the therapy, increase the cost of treatment.

Polyprigmas is quite often a forced measure when the elderly patient has a history of several pathologies. In such situations, the doctor seeks to simultaneously cure all the existing diseases, prevent the emergence of complications. But experts rarely take into account the absence, reduction or inverting the expected therapeutic effect on drug therapy against the background of changes in the metabolism of drugs in a fading body (the metabolism decreases, the volume of circulating blood decreases, renal clearance decreases).

According to statistical information, polypragmazia has the following disadvantages:

• Increases the risk of unwanted reactions 6 times. If a person takes more than 3 drugs at the same time, the probability of side effects rises 10 times;
• Reception 2 of medicines simultaneously provokes drug interaction in 6% of patients. When sharing 5 drugs, this parameter reaches 50%, when taking 10 preparations - 100%;
• Increases mortality OT side effect People of old age (over 80 years old).

In 80% of cases, doctors do not know what medications are accepted by patients, since older people are often observed at a neurologist, therapist, an oculist, cardiologist, a gastroenterologist, an endocrinologist, a urologist, otorinolaryngologist. Narrow specialists often prescribe their own treatment without taking into account the available recommendations of other doctors.

Why does polypragmazia arise?

Most medicines are obtained by synthetic pathway from various chemical components. Manufacturers clearly monitor drugs to eliminate the symptoms and causes of the disease, did not have a detrimental effect on the human body.

However, the improper use of drugs provokes unexpected drug interaction. As a result, chemical reactions occur not only between the initial ingredients of drugs, but also their active metabolites. This causes the formation of high-caliped complexes that cause severe generalized bullous dermatitis, epidermal necroliz.

Important! If on the background of the prescribed therapy in the patient there is no pronounced therapeutic effect, then the specialist can increase the dose of medication or prescribe a drug from a new generation.

Often, polypragmasia occurs due to improper selection of drugs, when the patient prescribe unidirectional or optional medicines. Also, people of old age are often found pharmacomy. This condition is a habit of using certain medicines even if they are ineffective.

Examples of drug interaction

During the appointment of therapy scheme, such reactions should be taken into account:

• Simultaneous reception of aspirin and caffeine-based means leads to the formation of toxic compounds;
• The sharing of sleeping and sedatives causes the destruction of vitamin D;
• St. John's wort is able to reduce the activity of statins, cyclosporin;
• The simultaneous intake of sulfanimamides and non-steroidal anti-inflammatory agents increases the toxicity of antibacterial medicines;
• Extract of Ginkgo Biloba, adopted with warfarin, increases the risk of bleeding;
• Prolonged treatment with antispasmodics against the background of using hypotensive drugs causes atonic constipation. Such a state requires the use of laxatives, which will only be exacerbated by heart failure;
• The sharing of systemic serotonin inefficient inhibitors with a drill increases the risk of serotonin crisis.

Important! Great influence on drugs can have food. Therefore, during the use of ampicillin, it should be abandoned by the use of milk, in the treatment of aspirin it will be necessary to eliminate the reception of fresh vegetables.

To prevent the occurrence of polypragmasia in the elderly patients, it is necessary to take into account the drug interaction of the designated drugs. Therefore, a family doctor should keep track of all the appointments of narrow specialists. The problem of polypragmazia is solved by the presence that adjusts the treatment regimen of each patient.

View- DPP advanced training

The name of the program: Polypragmazying therapeutic and prophylactic organization: problem and solution

The purpose of the program: Formation of doctors and organizers of healthcare competencies of the rational use of drugs under polypragmasia conditions in patients with combined pathology.

Student contingent: Health organizers, clinical pharmacologists, therapists, general practitioners, family doctors, cardiologists, pulmonologists, rheumatologists, nephrologists, gastroenterologists, endocrinologists, neurologists, pediatricians, surgeons.

Program Head: Head. Department of Clinical Pharmacology, D.M., Professor D.A. Sychev

Training period: 36 Acad. watch

Full-time form of education.

Occupation mode: 6 Acad. hour. In a day

Document issued: Certificate of advanced training

Uniqueness of the program: The program of the unique cycle provides coverage of the cause and clinical consequences of polypragmasia (including pharmacokinetic and pharmacodynamic intercommunical interaction), the principles of rational combination of drugs, measures for the prevention of adverse reactions due to the interstitial interactions in patients with connived pathology (including the elderly and senile age). The auditors are formed by the skill of the audit of drugs for drugs for the identification of not substantiated prescribed drugs, potentially dangerous and non-rational combinations, using information technologies (including computer programs, Internet resources for the forecasting of interspersonal interactions) - This approach is subject to using examples from real clinical practice (c. t.ch. and the listeners themselves). Modern methods of combating polypragmazia, proven its effectiveness in terms of improving the efficiency, safety of pharmacotherapy, reducing the number of non-rationally appointed drugs and their combinations, reducing treatment costs (Birca Criteria, Stopp-Start Criteria, Medicinal Rationality Index Holinergic load, risk management of problems associated with the use of drugs in the medical and prophylactic organization and other approaches).

Sign up on the online cycle:

Planned results:
A graduate, who finished training in the educational program "Polyprangmsia in a medical and preventive organization: a problem and solution" will have professional competencies:

• the ability to participate in identifying potentially hazardous combinations of drugs and potentially non-recommended drugs in sheets of drugs in patients with combined pathology;
• the ability to use information technologies to predict the development of clinically significant interstitial interactions in patients with combined pathology;
• the ability to reduce the number of non-rationally appointed drugs, combinations and reducing treatment costs under polypragmascus (criteria of the Birsca, StopP-Start Criteria, the Drug Rationality Index, the Holinergic Load Index, Risk Management of Problems related to the use of drugs in the medical and prophylactic organization and etc.).

A graduate, who finished learning on the educational program will acquire skills:

• audit of drugs for drugs to identify potentially not recommended drugs and potentially hazardous drug combinations in patients with combined pathology;
• use, as well as organize the introduction of modern methods for reducing the number of non-rationally prescribed drugs, combinations (birca criteria, STOPP-START criteria, index of the rationality of drugs, the Holinergic load index, etc.).

• rational use of drugs and their combinations in patients with combined pathology with polypragmazia;
• use of information technologies to optimize pharmacotherapy of patients with combined pathology with polypragmazia;