Polypharmacy in the elderly. Russian Medical Academy of Continuous Professional Education. Aspects of the problem of polypharmacy

Polypharmacy, prescribing poorly interacting drugs, insufficient information from doctors about more effective drugs, weak intradepartmental control, and the lack of a link between the attending physician and the pharmacist significantly reduce the effectiveness of pharmacotherapy.

The experience of foreign countries and individual medical institutions of the Russian Federation has demonstrated the feasibility of introducing a new medical specialty and position - "clinical pharmacologist". The introduction of specialists in clinical pharmacology into practical healthcare has improved the conduct of individual pharmacotherapy, contributed to the prevention, timely detection and treatment of side effects of drugs, ensured more expedient preparation of applications for medicinal products and control over the correct use of them.

Thus, the significance of clinical pharmacology in modern medicine is determined by:

A significant number of medicines on the Russian pharmaceutical market;

A large number of drugs with unproven efficacy and safety;

Population heterogeneity and significant variability in genetically determined responses to drug administration;

Too much low quality information about medicines;

The lack of official systematic data on the clinical efficacy of generic drugs;

Constant updating of the range of medicines;

Economic cost of drug therapy.

The work of a clinical pharmacologist also involves the creation of certain conditions for the successful implementation of his professional duties. This is the provision of an appropriate legal framework in a medical facility - the issuance of orders and orders that determine the range of rights and obligations of a specialist, the system of relations between a clinical pharmacologist and other specialists of a medical institution; organizational, technical and instrumental equipment of an office, department, laboratory; availability of computer equipment, access to the Internet.

What are the reasons for these requirements and why are they mandatory for a clinical pharmacologist?

Continuous improvement of professional training is associated with the peculiarities of the work of a specialist in this profile.

Given that the appointment of drugs in accordance with the Order of the Ministry of Health and Social Development No. 110 of February 12, 2007, “... is carried out based on the severity and nature of the disease ...”, knowledge of issues related to a particular disease is fundamental when prescribing pharmacotherapy. The same order determines the procedure for dosing DS: “Single, daily and course doses when prescribing medicines are determined by the attending physician based on the age of the patient, severity” and the nature of the disease in accordance with the standards of medical care. And in this regard, the role of a clinical pharmacologist as a consultant and expert obliges him to be guided in these issues.

All of the above implies that the clinical pharmacologist is able to use data on the pharmacodynamics and pharmacokinetics of the drug in relation to a particular clinical case.

In the definition of V.A. Gusel and I.V. Markov clinical pharmacology has the following sections:

Pharmacodynamics;

Pharmacokinetics;

Interaction of drugs;

Undesirable effects of drugs and methods for their prevention;

Methods for monitoring the effectiveness and safety of drugs;

Methods for clinical trials of drugs.

It is assumed that pharmacodynamics largely explains the mechanisms of development of the main clinical and side effects, depending on the age, sex of the patient, the nature of the underlying disease and comorbidity. Knowledge of pharmacokinetics allows you to choose the optimal method of drug administration, its dose, the possibility of combined use of drugs, dietary features.

Given the high variability of the pharmacokinetic characteristics of drugs associated with the state of the patient's body and depending on genetic mechanisms, the severity of the disease, in some cases it is necessary to carry out drug monitoring (determination of the concentration of the drug in the blood). This allows you to individualize the ongoing drug therapy, increase its effectiveness and safety. This approach is essential when prescribing drugs with a narrow "therapeutic window" or "therapeutic range", i.e. for substances that have a small concentration range from causing a minimal therapeutic effect to the first signs of side effects.

Genetic factors also influence the pharmacodynamics and pharmacokinetics of drugs. It is pharmacokinetics that largely explains the individual characteristics of the reaction to the use of drugs, such as low or high sensitivity to the drug, intolerance. Pharmacokinetics is essential for the individualization of pharmacotherapy and in determining the appropriateness of prescribing several drugs.

Coordination with the head of the department, and in emergency cases - with the responsible doctor on duty or another person authorized by order of the head physician of the medical institution, as well as the clinical pharmacologist is necessary in the following cases:

a) simultaneous administration of five or more drugs to one patient

The appearance of guidelines limiting the number of drugs prescribed simultaneously is associated with the difficulty of determining the possible benefits and harms of such combinations, i.e., the difficulty of predicting the results of drug interactions. “Drug interaction is understood as the effect of one drug on the effects of another when used simultaneously. As a result of the action of one of the drugs (or both), it is weakened or enhanced, or a new effect occurs that is not characteristic of each of them individually ”(Clinical Pharmacology according to Goodman and Gilman, 2006). According to various authors, up to 25% of the combinations used are potentially dangerous. The risk of side effects increases in proportion to the number of drugs used. Taking into account the widespread use of polypharmacy (prescribing an unreasonably large amount of drugs) and polytherapy (simultaneous treatment of all diseases present in a patient), as indicated in the letter of the Ministry of Health of the Russian Federation dated December 28, 2000 “On measures to strengthen control over the prescription of drugs”, doctors of all specialties , including clinical pharmacologists, must understand the inefficiency, potential danger and economic cost of such an approach.

The use of drugs always carries a risk, but the degree of risk changes significantly with an increase in the number of prescribed drugs. At the same time, it must be remembered that a side effect is an inherent property of a drug, and the manifestation of its damaging effect on the body can and should be predicted.

The doctor's task is to anticipate the possibility of adverse side reactions, to carry out their prevention, and, if an undesirable effect develops, to be able to eliminate it.

In the Russian Federation, there are no systematic data on the side effects of drugs. This is due to various reasons. The order of the Ministry of Health of the Russian Federation No. 114 dated April 14, 1997 “On the establishment of the Federal Center for the Study of Side Effects of Drugs of the Ministry of Health of Russia” was not implemented in the country. So far, a system has not been created to identify and record adverse adverse reactions. However, doctors should be aware that when adverse reactions are detected, they are obliged “... to report to the federal executive body responsible for state control and supervision in the field of healthcare, and its territorial bodies, about all cases of side effects of drugs and about the features of the interaction of drugs with other medicines that do not correspond to the information about medicines contained in the instructions for their use ”(Article 41 of the Federal Law“ On Medicines ”). Further, the Law states: “For failure to disclose or conceal information provided for in paragraph 1 of this article, persons who have become aware of them by the nature of their professional activities shall bear disciplinary, administrative or criminal liability in accordance with the legislation of the Russian Federation.”

Drug assistance to the population is not only a clinical problem, but also an economic one. In this regard, it is appropriate to quote the words of A. Donabedian: "The highest price of drug care occurs when treatment is carried out incorrectly."

The economic evaluation of pharmacotherapy is of interest to those responsible for the formation of drug policy in the country, region, specific health facility. Estimating the cost of drug therapy is important for the whole society as a whole and for a particular patient in particular. The internationally accepted definition of rational use of drugs: “…delivering pharmacotherapy adequate to the clinical condition of the patient, at doses appropriate to his individual characteristics, in due time and at the lowest cost” (Managing Drug Supply, 1997) - also involves an economic assessment.

The economic orientation of the analysis of proposed treatment regimens makes it possible to correlate the possibilities of the state and specific people in paying for medicines, in choosing specific drugs in the formation of formulary lists, and the preparation of treatment standards.

It was these circumstances that determined the need for the emergence and development of pharmacoeconomics. As defined by the International Society for Pharmacoeconomics Research (ISPOR, 1998), “Pharmacoeconomics is a field of study that evaluates the characteristics of individuals, companies, and the market in relation to the use of pharmaceutical products, medical services, programs, and analyzes the value (costs) and consequences of the results of this use.” In order to unify approaches to conducting and using the results of clinical and economic studies, the Ministry of Health of the Russian Federation dated May 27, 2002 No. 163 approved the industry standard “Clinical and Economic Studies. General Provisions". One of the tasks that should be solved taking into account the provisions of this document is "justifying the choice of medicines and medical technologies for the development of regulatory documents that ensure their rational use."

Another area of ​​modern medicine and pharmacy in which the methodology of clinical pharmacology is actively used is clinical drug trials. Working in this field requires a clinical pharmacologist not only to have knowledge and skills in the field of medicine, but also to be trained in legal and ethical issues.

Considering that clinical trials have been expanding in recent years and are being conducted in many health facilities, this issue should be under the control of clinical pharmacologists, which will ensure high quality of research and increase their safety for patients.

L.B. Lazebnik, Yu.V. Konev, V.N. Drozdov, L.I. Efremov
Department of Gerontology and Geriatrics, Moscow State University of Medicine and Dentistry; Organizational and methodological department for therapy of the Moscow Department of Health; Central Research Institute of Gastroenterology

Polypharmacy [from "poly" - a lot and "pragma" - an object, a thing; synonym - polytherapy, excessive treatment, polypharmacy, "polypharmacy" (English)] - the redundancy of medical prescriptions has been and remains a very widespread and little-studied problem in modern clinical medicine.

The most well-known drug or drug polypharmacy (polypharmacy, polypharmacotherapy) is the simultaneous administration of several drugs in elderly patients. "Massive drug strike" (the author's term), as a rule, receives the most vulnerable contingent of patients, i.e. people suffering from polymorbidity - simultaneously occurring several diseases in various phases and stages. Most often these are elderly patients.

The number of diseases per patient in a geriatric hospital is shown in Fig. 1.

It is noteworthy that with increasing age, the index "number of diseases/one patient" decreases. This happens for several reasons. Firstly, people who suffer from fewer chronic diseases live to advanced years. Secondly, some chronic diseases are known to involute or disappear with age (for example, duodenal ulcer). Thirdly, under the influence of treatment, many diseases acquire a different clinical form ("drug" or "iatrogenic polymorphosis"). Examples are the transformation of a painful form of coronary heart disease into a painless form during long-term treatment with antianginal drugs or the disappearance of angina attacks and the normalization of blood pressure after implantation of a pacemaker.

It is polymorbidity, which forces the patient to be observed simultaneously by doctors of several specialties, is the reason for drug polypharmacotherapy as an established practice, since each of the specialists observing the patient, according to standards or established practice, is obliged to carry out targeted appointments.

On fig. 2 shows the profiles of doctors who simultaneously observe an elderly outpatient in one of the Moscow polyclinics.

Our long-term experience of clinical and expert assessment of the quality of medical and diagnostic care shows that in most cases the principle that the attending physician follows when prescribing several drugs to the patient at the same time reflects his desire to cure all the diseases that the patient has at once (preferably, quickly), and at the same time prevent all possible complications (preferably more reliable).

Guided by these good intentions, the doctor prescribes drugs known to him according to the usual schemes (sometimes "for pressure", "for constipation", "for weakness", etc.), at the same time thoughtlessly combining the generally correct recommendations of numerous consultants who consider how It has already been mentioned above that it is mandatory to introduce additional treatment according to your profile.

As an example, we cite the simultaneous prescription of 27 different drugs in the amount of more than 50 tablets per day to a disabled veteran of the Great Patriotic War (we are talking about drug provision under the DLO system), and the patient not only insisted on receiving them, but also took everything! The patient suffered from twelve diseases and was seen by eight specialists (therapist, cardiologist, gastroenterologist, neurologist, endocrinologist, urologist, ophthalmologist and otorhinolaryngologist), each of whom prescribed "his" treatment, without even trying to somehow correlate it with the recommendations of other specialists. Naturally, the therapist raised the alarm. Believe me, it cost a lot of work to convince the patient to stop taking a huge amount of drugs. The main argument for him was the need to "pity the liver."

The problem of polypharmacotherapy has been around for a long time.

Being the head of the Department of Pharmacology of the Military Medical Academy in 1890-1896, I.P. Pavlov once wrote: "... When I see a prescription containing a prescription for three or more drugs, I think: what a dark power lies in it!" It is noteworthy that the mixture proposed by I.P. Pavlov in the same period, named after him, contained only two drugs (sodium bromide and caffeine), acting in different directions on the functional state of the central nervous system.

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

According to I.P. Pavlov, polypharmacy should be considered the simultaneous appointment of three or more drugs to the patient, and according to P. Erlich, more than one.

There are several reasons for drug polypharmacotherapy, both objective and subjective.

The first objective reason is, as we have already pointed out, senile polymorbidity ("redundancy of pathology"). The second objective reason in geriatrics is the absence, weakening or inversion of the expected final effect of the drug due to a change in drug metabolism in a fading organism with naturally developing changes - a weakening of metabolic processes in the liver and tissues (including the activity of cytochrome P450), a decrease in the volume of circulating blood, decreased renal clearance, etc.

Getting an insufficient or perverted effect from the prescribed drugs, the doctor changes the treatment most often in the direction of increasing the number of pills or replacing the drug with a "stronger" one. As a result, iatrogenic pathology develops, which was previously called "drug disease". Now such a term does not exist: they talk about "undesirable" or "side" effects of drugs, hiding behind the terms the inability or unwillingness to see the systemic effect of the active substance on the human body as a whole.

A careful analysis of the gradual development of numerous diseases in the elderly makes it possible to identify syndromes that characterize the systemic effects of drugs in the body of an old person - psychogenic, cardiogenic, pulmogenic, digestive, enterogenic, hepatogenic, otogenic, etc.

These syndromes, caused by prolonged exposure to drugs on the body, clinically look and are regarded by the doctor as a disease per se or as a manifestation of natural aging. We believe that a doctor reflecting on the essence of things should pay attention to the accelerated pace of development of the newly recorded syndrome and try to at least chronologically connect it with the time the drug was started. It is the rate of development of the "disease" and this connection that can tell the doctor the true genesis of the syndrome, although the task is not easy.

These final systemic effects that develop with long-term, often long-term use of drugs by elderly people are almost always perceived by the doctor as a manifestation of aging of the body or the addition of a new disease and always entail additional prescription of drugs aimed at curing the "newly discovered disease".

So, long-term use of antispasmodics or some antihypertensive drugs can lead to atonic constipation, followed by prolonged and most often unsuccessful self-medication with laxatives, then to intestinal diverticulosis, diverticulitis, etc. At the same time, the doctor does not assume that constipation has changed the intestinal flora, the degree of hyperendotoxinemia has increased, exacerbating heart failure. The doctor's tactic is to intensify the treatment of heart failure. The prognosis is clear. Dozens of such examples could be cited.

Simultaneous administration of drugs leads to drug interactions in 6% of patients, 5 increases their frequency to 50%, when taking 10 drugs, 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 drug-related adverse reactions.

The average number of drugs taken by older patients (both prescribed by doctors and self-administered) was 10.5, while in 96% of cases, doctors did not know exactly what their patients were taking.

On fig. 3 shows the average daily number of drugs taken by patients in a geriatric hospital (according to our employee O.M. Mikheev).

Physically more active people took fewer drugs, and with increasing age, the amount of drugs consumed decreased, which confirms the well-known truth: less sick people live longer.

From the objective causes of drug polypharmacotherapy, subjective ones follow - iatrogenic, caused by the appointments of a medical worker, and discompliant, due to the actions of the patient receiving treatment.

The basis of iatrogenic causes is primarily a model of diagnostic and treatment tactics - treatment should be complex, pathogenetic (with an impact on the main links of pathogenesis), and the examination should be as complete as possible. These, in principle, absolutely correct foundations are laid down in the undergraduate doctor's training programs, programs and postgraduate education.

Education on the interaction of drugs cannot be considered sufficient; doctors have very little knowledge of the relationship between drugs, nutritional supplements and meal times. It is not uncommon for a doctor to make a decision to prescribe a drug, being under the suggestive influence of recently received information about the miraculous properties of the next pharmaceutical novelty, confirmed by the "unique" results of the next multicenter study. However, for advertising purposes, it is silent that patients were included in such a study according to strict criteria, excluding, as a rule, a complicated course of the underlying disease or the presence of other "comorbid" diseases.

Unfortunately, we have to state that in undergraduate and postgraduate education programs very little attention is paid to the problem of in vivo compatibility of drugs, and the issues of long-term use of this drug or drugs of this pharmacological group are not touched upon at all. Opportunities for self-education of a doctor in this area are limited. Not everyone has access to compatibility tables for two drugs, and as for three or more, it seems that modern clinical pharmacology has not yet begun to search for an answer to this vital question.

At the same time, it should be noted that we ourselves can form an idea of ​​this only on the basis of long experience. Reasonable arguments, based on many years of observation, made it possible to abandon the recommendations for lifelong use of estrogen replacement therapy; be wary of recommendations for lifelong use of proton pump inhibitors, etc.

Volens nolens, even a highly educated thinking doctor who starts treating a patient with polymorbidity, every time he has to work in a cybernetic "black box" system, i.e. situations where the decision maker knows what he inputs into the system and what he should get as output, but has no idea about the internal processes.

The main reason for polypharmacotherapy on the part of the patient is discompliance with medical prescriptions.

According to our research, up to 30% of patients did not understand the doctor's explanations regarding the names, the regimen of taking drugs and the goals of treatment, and therefore took up self-medication. About 30%, after listening to the doctor and agreeing with him, independently refuse the prescribed treatment for financial or other reasons and change it, preferring to supplement the recommended treatment or the usual (essentially ineffective) medicines or remedies that they were advised to use by friends, neighbors, relatives or other medical (including ambulance) workers.

A significant role in perverting the treatment is also played by aggressive advertising of nutritional supplements, which are presented by the media as a "unique remedy ..." ("order urgently, stock is limited ..."). The effect of uniqueness is enhanced by the reference to the mysterious ancient Eastern, African or "Kremlin" origin. The "guarantee" of the effect is sometimes laid down in the name of the product or the hypocritical recommendation to consult a doctor, who, even with a great desire, will not find any objective information about this miracle remedy. References to the popularity of the "ancient remedy" in the claimed country of origin are untenable: questions asked in this country about this "remedy" cause bewilderment among the local population.

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

Given all of the above, one cannot help but welcome the creation of a Corresponding Member headed by. RAMS prof. V.K. Lepakhin of the Federal Center for Monitoring the Safety of Medicines of Roszdravnadzor.

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

We single out rational and irrational variants of pharmacotherapy for polymorbidity. The condition for successful application and achievement of the goal with a rational option is the competence of the doctor and the patient. In this case, the effect is achievable using a reasonable technology, when, due to clinical necessity and pharmacological safety, the patient is prescribed several drugs or forms at the same time.

In the presence of several diseases, it is necessary to prescribe drugs with a proven absence of interaction. To achieve a greater effect in the treatment of one disease in order to potentiate one effect, single-acting drugs are prescribed in the form of several dosage forms of different names or in the form of ready-made dosage forms of factory production (for example, an angiotensin-converting enzyme inhibitor and a diuretic in one tablet - "polypills", in the form tablets of several drugs differing in chemical composition, but sealed in one blister, and even with an indication of the time of administration, etc.).

Another option for rational pharmacotherapy for polymorbidity is the principle of multipurpose monotherapy that we are developing, i.e. simultaneous achievement of a therapeutic goal in the presence of a systemic effect of this drug.

Thus, the indications for prescribing the α-blocker doxazosin for men suffering from arterial hypertension and prostatic hyperplasia, included in the European and national recommendations, were developed in detail by our employee E.A. Klimanova, who also showed that when prescribing this drug, it is possible to correct mild forms of insulin resistance and hyperglycemia. Another of our collaborators, M.I.Kadiskaya, for the first time showed the systemic non-antilipidemic effects of statins, later called pleiotropic.

We believe that it is multitarget monopharmacotherapy that will largely allow avoiding those irrational options for pharmacotherapy in polymorbidity, which are presented in the right columns of the scheme and which were mentioned above.

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

Reasonable drug polypharmacotherapy in modern clinical practice, subject to its safety and expediency, is not only possible and acceptable, but necessary in difficult and difficult situations.

Unreasonable, incompatible, simultaneous or within 1 day prescribed a large number of drugs to one patient should be considered irrational polypharmacy or "drug polypharmacy".

It is appropriate to recall the opinion of the famous therapist I.Magyar (1987), who, based on the principle of the unity of the treatment and diagnostic process, proposed a broader interpretation of the concept of "polypharmacy". He believes that therapeutic polypharmacy is often preceded by diagnostic polypharmacy (excessive actions of a doctor aimed at diagnosing diseases, including using ultra-modern, as a rule, expensive research methods), and diagnostic and therapeutic polypharmacy, closely intertwined and provoking each other, give rise to countless iatrogenic. Both types of polypharmacy are generated, as a rule, by "undisciplined medical thinking".

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

On the one hand, it is impossible not to admit that many doctors, especially young ones, who have little knowledge of clinical diagnostics, of the non-interchangeability and complementarity of different diagnostic methods, prefer to prescribe "additional" examinations ("instrumentalism" from ignorance!), Having received a conclusion, they often do not even bother getting to know him. In addition, a rare doctor in modern practice accompanies the patient during diagnostic manipulations, is limited to a ready-made conclusion and does not delve into the structure of the original indicators.

The huge workload of laboratories and technical diagnostic services is due to approved standards and diagnostic schemes, which do not always take into account the material, technical and economic capabilities of a given medical facility.

The diagnostic component of the cost of the treatment and diagnostic process is steadily increasing, the financial needs of modern health care cannot be sustained by the economy of even highly developed countries.

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

Each doctor can give more than one example when a severe or prognostically unfavorable disease was detected during an accidental ("just in case"!) Diagnostic manipulation. Each of us is a supporter of an early and ongoing cancer search.

Modern diagnostic systems are practically safe for health, the manipulations used in their implementation are easily tolerated, so the concept of "benefit-harm" becomes conditional.

Apparently, speaking about the modern aspects of "diagnostic polypharmacy", one should keep in mind the "goal-cost" rationale.

We deliberately use the concept of "goal", which is replaced by the term "expediency" in some guidelines on pharmacoeconomics. Some politicians-economists who are not ready for key roles easily substitute economic "expediency" for the ethical concept of "goal". So, according to the opinion of some of them, the state provision of the medical and diagnostic process is inappropriate, etc.

The aim is to detect a chronic disease as early as possible. Thus, the conclusion suggests itself that it is necessary to conduct a detailed medical examination multiple times throughout a person’s life, i.e. medical examination, which implies the obligatory obtaining of results using laboratory, endoscopic and radiation technologies.

Based on the Moscow experience, we believe that such an option for the development of healthcare is possible.

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

We believe that in order to prevent unreasonable diagnostic and therapeutic polypharmacy in people of older age groups, the attending physician must adhere to the following fundamental provisions.

1. The risk of examination should be less than the risk of an unidentified disease.
2. An additional examination must be prescribed primarily to confirm, but not to reject a preliminary diagnosis, which must be substantiated.
3. Follow the rule formulated by the famous therapist and clinical pharmacologist B.E. Votchal: "Less drugs: only what is absolutely necessary" . The absence of direct indications for prescribing the drug is a contraindication.
4. Adhere to a "low dose regimen" for almost all drugs, except for antibacterials ("only the dose makes the medicine poison"; however, the opposite is also true: "only the dose makes the poison medicine").
5. Correctly choose the ways of removing drugs from the body of an elderly person, giving preference to drugs with two or more ways of excretion.
6. Each appointment of a new drug must be carefully weighed, taking into account the peculiarities of the drug's action (pharmacokinetics and pharmacodynamics) and the so-called side effects. Note that the patient himself should be familiarized with them. Prescribing a new medicine, you need to think about whether it is worth canceling some "old" one.

The presence in an elderly patient of multiple pathologies, mosaic and blurring of clinical manifestations, a complex and bizarre plexus of complaints, symptoms and syndromes caused by clinical manifestations of aging processes, chronic diseases and medicinal effects (Fig. 6), make treatment a creative process, in which the best solution is possible only thanks to the mind of the doctor.

Unfortunately, modern specialists, especially narrow ones, have begun to forget a long-established simple rule that allows avoiding drug polypharmacy: the patient (of course, except for urgent situations) should not receive more than 4 drugs at the same time, and issues of increasing the volume of treatment should be decided jointly by several specialists (concilium) . With a joint discussion, it is easier to predict a possible drug interaction, the reaction of the whole organism.

When treating each specific patient, one should act according to the old commandments: "est modus in rebus" (observe the measure) and "non nocere" (do no harm).

Literature

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Polypharmacy is the No. 1 problem in modern medicine and pharmacology. The reason is polymorbidity. The joint use of 3 or more drugs prescribed by different specialists for the treatment of several diseases occurring together can cause complications

Polypharmacy is the No. 1 problem in modern medicine and pharmacology. The reason is polymorbidity.

The combined use of 3 or more drugs prescribed by different specialists for the treatment of several diseases occurring together can cause complications of drug therapy.

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Therefore, the problems of polypharmacy require careful consideration and prompt resolution.

Is polypharmacy a necessity?

A special place is occupied by polypharmacy in gerontology. Studies show that it is among elderly patients with metabolic disorders that cases of unjustified polypharmacy are most common, when patients take more than 7 drugs prescribed by different specialists.

Ongoing studies state that when taking more than two drugs at the same time, it is extremely difficult to foresee their mutual influence on each other and on the patient's body.

Consultation: Polypharmacy - as a problem of drug therapy

The main goal of medicine is to extend the life of a person (up to 80–90 years). But the whole question is the quality of such a being: it is important that longevity is not a burden. And without drugs, even against the background of proper nutrition and a reasonable lifestyle, this is impossible to do.

The flip side of long old age is polypharmacy. The simultaneous appointment, often unjustified, of many drugs is the most acute problem of pharmacotherapy. Any drug interacts with various products of a chemical nature that enter the body. The possibility of physical or chemical interaction makes many medicinal substances incompatible, their simultaneous administration leads to inactivation or the formation of toxic compounds.

A person with a large number of diseases is sometimes forced to take dozens of drugs at the same time, and it is not easy to foresee how they will react to each other. Only a competent doctor can assess all the risks, so there can be no talk of any self-treatment here.

Pharmacologists believe that a high-quality generic drug has a great advantage in this sense: they start producing it only when the original drug has worked out. If it has shown any severe effects, then it simply leaves the market, and the creation of its generics is impossible.

Modern statistics are as follows: simultaneous intake of more than 3 drugs can cause resistance within 6%, when taking more than 5 drugs, the complications of drug therapy increase to 50%, simultaneous intake of more than 10 drugs is accompanied by 100% resistance.

General problems of drug pathology

Self-medication and aggressive therapy

A multiple increase in the drug load on the patient is associated with an excessive interest in antibiotic therapy, even in cases where this therapy is excessive.

Based on data from studies conducted in the 90s of the 20th century in the territory of the former Soviet Union, the prescription of antibiotics in outpatients with uncomplicated cases reached 70–90% (Fedorov A. M., Salomova S. R. Polypharmacy in pediatrics // PF. 2009. No. 5 S.107-109.).

The widespread fascination with antibiotics has caused the population to have an erroneous idea about.

Today, more and more often we have to meet situations of self-treatment, an increasing number of patients admit that they “keep on hand” antibiotics.

Such aggressive therapeutic behavior leads to the emergence of allergenic patients, and to an increase in antibiotic-resistant strains.

The results of the comparative analysis of Kharakoz, Zubareva, Ponomareva and Kompaniets showed that:

• 21% of patients among all recorded cases of polypharmacy in the LU combine the simultaneous use of drugs prescribed by the attending physician and those that they prescribed themselves after seeing a television advertisement for the drug or purchasing it on the recommendation of a neighbor.
• Moreover, in 4.6% of cases, the fact of incompatibility of taking medications was recorded.

These studies indicate the need to update the topic among the population, and especially in patients prone to self-treatment. (Bulletin Health and education in the XXI century, 2008, No. 6 p.293).

Complications of drug therapy

The redundancy of medical prescriptions and multiple drug therapy - the main causes of polypharmacy - entail adverse reactions (resistance, allergization, anaphylactic shock, etc.) and put the specialist in front of a difficult choice.

The most common drugs that cause adverse reactions

NSAIDs (NSAIDs, NSAIDs, NSAIDs)	Used for anti-inflammatory, antipyretic, analgesic purpose.
Vitamin K antagonist (warfarin), clopidogrel	used for antithrombotic purposes.
Diuretics, ACE inhibitors, and angiotensin II receptor blockers (ARBs)	used for antihypertensive purposes.
Beta blockers	Used to reduce the frequency and strength of the heartbeat, prevent the expansion of the vessels of the heart, reduce the muscle load on the heart, and reduce tremor.
Opiates	Used as strong painkillers.
Prednisolone	Used to stop severe allergic reactions, it itself can cause anaphylactic shock, as it is a xenobiotic.

Reasons for the ineffectiveness of pharmacotherapy

1. Joint excessive intake of drugs becomes the reason for the ineffectiveness of pharmacotherapy.
2. Individual features of the patient:

• height;
• Lifestyle;

1. Eating habits and associated drug use patterns are also a cause of drug therapy complications.

Reference: Attention to the problem of polypharmacy was riveted already in the 19th century by Academician Pavlov I.P., who believed that simultaneous prescription of more than three drugs should be considered polypharmacy: “When I see a prescription containing a prescription for three or more drugs, I think: what a dark The power is in him!" Modern pharmacotherapy knows a paradoxical case when an elderly patient, a veteran of the Great Patriotic War, was prescribed the simultaneous intake of 27 drugs, which in total amounted to about 50 tablets per day!

We believe that independent, uncontrolled or simultaneous use of several unidirectional, mutually exclusive, unnecessary drugs and drugs without taking into account side effects can have negative consequences.

This type of therapy should be attributed to unreasonable drug polypharmacy.

The necessary and possible (rational) drug combinations for simultaneous use or the use of systemic effects of drugs for the complex, effective treatment of several synchronously occurring diseases should be attributed to reasonable polypharmacotherapy.

Generics as a possible solution to polypharmacy

Russia is in the top three leading countries in terms of consumption of generics. Due to the significantly low cost of these drugs, they are gaining more and more popularity. But the essence of the priority of generics is not only in an attractive low price.

It is important that when creating high-quality generics, all the complications of drug therapy that have arisen at the time of taking the original drug are taken into account.

When choosing generics, it is necessary to rely on the criteria for their safety and quality, confirmed by international experience in their use.

According to Zhuravleva M.V., Professor of the Medical Faculty of the PMSMU named after. I. M. Sechenov, Chief Specialist of Clinical Pharmacology of the Moscow Department of Health, Doctor of Medical Sciences, an important task facing pharmacologists is to create highly effective, high-quality, non-resistant generics.

In the modern system, before diploma and postgraduate education, almost no attention is paid to the issues of polypharmacy. The future of pharmacology, of course, should pay special attention to this area of ​​pharmacotherapy.

And in this sense, it is generics that have a great future, because their production begins only after 10 years of mass use of the original drug, when a huge clinical base has been collected, data on all possible side effects are known. Moreover, if there are too many of these data or they are insurmountable, the drug leaves the market and the creation of a generic is impossible.

Polypharmacy (polypharmacy) is a widespread problem of modern clinical medicine, which arises as a result of excessive prescribing of drugs by specialists. This phenomenon is more common in older people who suffer from several diseases at the same time.

What is the problem?

Polypharmacy is a common tactic in the treatment of many pathologies. Therefore, in a hospital or outpatient therapy, the patient often receives simultaneously from 2 to 10 drugs. At the same time, the number of drugs is determined by the severity of the condition, the presence of concomitant pathologies, the alertness of the specialist and the patient.

Important! The combined use of several drugs can increase the risk of adverse reactions and interactions between drugs, reduce patient adherence to therapy, and increase the cost of treatment.

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

According to statistics, polypharmacy has the following disadvantages:

• Increases the risk of adverse reactions by 6 times. If a person takes more than 3 drugs at the same time, then the likelihood of side effects increases 10 times;
• Taking 2 medications at the same time provokes drug interactions in 6% of patients. With the joint use of 5 drugs, this parameter reaches 50%, when taking 10 drugs - 100%;
• Increases mortality from side effects in the elderly (over 80 years).

In 80% of cases, doctors do not know what medications patients are taking, since older people are often observed immediately by a neurologist, internist, ophthalmologist, cardiologist, gastroenterologist, endocrinologist, urologist, otorhinolaryngologist. Narrow specialists often prescribe their own treatment, not taking into account the recommendations of other doctors.

Why does polypharmacy occur?

Most medicines are obtained synthetically from various chemical components. Manufacturers make sure that medicines can eliminate the symptoms and causes of the disease and do not have a detrimental effect on the human body.

However, misuse of drugs provokes unforeseen drug interactions. As a result, chemical reactions occur not only between the original ingredients of drugs, but also their active metabolites. This causes the formation of highly allergenic complexes that cause severe generalized bullous dermatitis, epidermal necrolysis.

Important! If, against the background of the prescribed therapy, the patient does not have a pronounced therapeutic effect, then the specialist can increase the dose of the medication or prescribe a drug from a new generation.

Often, polypharmacy occurs due to the wrong choice of drugs, when the patient is prescribed unidirectional or optional medications. Pharmacomania is also often found in elderly people. This condition is a habit of using certain medicines even if they are ineffective.

Examples of drug interactions

When prescribing a treatment regimen, the following reactions should be considered:

• The simultaneous use of Aspirin and caffeine-based products leads to the formation of toxic compounds;
• The combined use of sleeping pills and sedatives causes the destruction of vitamin D;
• St. John's wort is able to reduce the activity of statins, Cyclosporine;
• Simultaneous administration of sulfonamides and non-steroidal anti-inflammatory drugs increases the toxicity of antibacterial drugs;
• Ginkgo Biloba extract taken with Warfarin increases the risk of bleeding;
• Long-term treatment with antispasmodics against the background of the use of antihypertensive drugs causes atonic constipation. This condition requires the use of laxatives, which will only aggravate the course of heart failure;
• The combined use of systemic serotonin reuptake inhibitors with St. John's wort increases the risk of a serotonin crisis.

Important! Food can have a big impact on drugs. Therefore, during the use of Ampicillin, you should stop drinking milk, while treating with Aspirin, you will need to exclude the intake of fresh vegetables.

To prevent the occurrence of polypharmacy in elderly patients, it is necessary to take into account the drug interaction of the prescribed drugs. Therefore, the family doctor must track all appointments of narrow specialists. The problem of polypharmacy is solved by the presence, which corrects the treatment regimen for each patient.

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

SUMMARY: The article deals with the problem of using combinations of antipsychotics. To date, the gap between the results of evidence-based medicine and the real daily practice of a doctor in combination therapy with antipsychotics is quite large. Based on literature data, an overview of the causes and negative consequences of antipsychotic polypharmacy is presented, as well as clinical situations in which it is justified are described. The results of the studies allow recommending combination antipsychotic therapy for patients who have not responded to at least three courses of antipsychotic monotherapy, including clozapine; if possible, augment antipsychotic therapy with drugs of other classes; if antipsychotic polypharmacy is inevitable, take into account the doses of drugs (risperidone and chlorpromazine equivalents). It is worth emphasizing that the majority of patients undergoing combination antipsychotic therapy are able to safely transition to antipsychotic monotherapy, thereby reducing treatment costs and increasing compliance.

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

Clinical guidelines for the optimal use of psychotropic drugs are widely available, but their prescription in real-life settings of daily practice usually differs from the proposed algorithms. Polypharmacy, the use of high doses of antipsychotic drugs, and maintenance treatment with benzodiazepines or anticholinergics are not well evidenced and can cause serious adverse effects.

Antipsychotic polypharmacy is the combination of two or more antipsychotic drugs. Opinions on the time criteria for ascertaining polypharmacy differ: some authors considered combined therapy for 14 days as polypharmacy, others - 60 or 90 days. E. Leckman-Westin and co-authors (2014) expressed the opinion that the most appropriate, expedient measure is a period of more than 90 days with a possible break of 32 days, since this period is characterized by a sensitivity of 79.4% and a specificity of 99.1%. Brief episodes of combination antipsychotics may be present when changing therapy, switching from one drug to another, which is consistent with current treatment strategies.

Antipsychotic polypharmacy continues to be a common phenomenon both in domestic and foreign clinical practice. The prevalence of polypharmacy of antipsychotics, according to various studies, ranges from 7 to 50%, and in most sources it ranges from 10 to 30%. An analysis of a significant number of studies with almost 1.5 million participants (82.9% with schizophrenia) showed that the average incidence of antipsychotic polypharmacy in the world is 19.6%. The most frequently used combination therapy option is a combination of first and second generation antipsychotics (42.4%), followed by a combination of two first generation antipsychotics (19.6%), followed by a second generation (1.8%). During the period from the 1970s to the 2000s, the average frequency of use of antipsychotic polypharmacy did not change significantly (1970–1979: 28.8%; 1980–1989: 17.6%; 1990–1999: 22.0%; 2000– 2009: 19.2%, p = 0.78). However, there are notable regional differences: in Asia and Europe, polypharmacy is more common than in North America, and in Asia more often than in Oceania. Differences in the prevalence of polypharmacy may be due to different demographic and clinical characteristics of the samples, as well as different study durations. The highest prevalence of antipsychotic polypharmacy is observed in patients in psychiatric hospitals (more than half of the patients). Its prescription correlates with the use of first-generation antipsychotics and correctors, the presence of a diagnosis of schizophrenia, the rarer use of antidepressants, and the more frequent use of prolonged forms of antipsychotics.

The results of a 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 the relative resistance of some patients to antipsychotic monotherapy in moderate doses. . According to the available data, 40% of psychiatrists prefer to use combinations of “classic” antipsychotics when relieving exacerbations. 10% of doctors prefer to add a second antipsychotic to the treatment regimen when the first is not effective enough, and the vast majority of specialists increase the dose. 7.5% of the doctors surveyed expressed their preference for using combinations of antipsychotics to prevent recurrence of the disease. It turned out that psychiatrists working in men's departments prefer to use combinations of two or more antipsychotics (mainly traditional ones) to relieve exacerbations of schizophrenia, but practically do not use monotherapy with second-generation antipsychotics for these purposes. Probably, this kind of preference is due to the desire to quickly reduce the disorganization of behavior, impulsivity and aggressiveness, which are known to be more pronounced in male patients. A certain role, apparently, is played by the distress that occurs in psychiatrists when working with the heaviest contingent of patients. Most doctors working in the women's departments of the hospital prefer to use monotherapy with a first-generation antipsychotic, although among them there are supporters of polypharmacy. Only psychiatrists working in the rehabilitation department opted for monotherapy. Among psychiatrists with more than 10 years of experience, the proportion of "polypragmatists" reaches a maximum, apparently due to outdated stereotypes of treatment.

There is no doubt that antipsychotic polypharmacy is not justified enough. Combination therapy is often prescribed without sufficient justification and the possibility of drug interactions is underestimated. So, about a fifth of outpatients with schizophrenia, along with long-acting antipsychotics, additionally receive traditional antipsychotics or, more recently, atypical antipsychotics by mouth, which can completely neutralize the positive features of their clinical action.

Evidence for the effectiveness of polypharmacy is found only in small randomized controlled clinical trials, case reports and is often based on the personal experience of the physician. There are practically no preclinical studies of antipsychotic combinations, although options for augmenting antipsychotic therapy with drugs of other classes are being studied. Quite a lot of attention is paid to identifying the antipsychotic potential of compounds, side effects are studied in animals, but this does not apply to combined antipsychotic therapy.

There is currently no consensus on the consequences of antipsychotic polypharmacy. Most studies suggest that antipsychotic polypharmacy is associated with a range of negative effects, including an increased risk of side effects compared to monotherapy and increased health care costs.

On the example of the analysis of 575 case histories, E.V. Snedkov and K. Badri demonstrated that the use of combinations of antipsychotic drugs is associated with a lower quality of remissions, which may be due to a number of factors, including the greater severity of the mental state, the presence of therapeutic resistance and low patient compliance. The likelihood of side effects increases in proportion to the number of prescribed drugs.

The most convincing adverse effects of antipsychotic polypharmacy are shown for extrapyramidal side effects accompanied by the use of anticholinergic drugs to increase prolactin levels. Both of these side effects can be explained by the higher total dose and blockade of dopamine receptors. Although reducing the doses of each drug when combined may help reduce side effects, the likelihood of their effectiveness may be reduced more likely. The divergence of data on the frequency of akathisia in antipsychotic polypharmacy supports the hypothesis that it is not primarily associated with the dopaminergic system. This is consistent with the frequent lack of effect of anticholinergic drugs, in contrast to beta-blockers and benzodiazepines. In addition, antipsychotic polypharmacy is associated with an increased risk of metabolic syndrome. Evidence of an increased risk of side effects such as parkinsonism, hyperprolactinemia, hypersalivation, sedation and drowsiness, cognitive impairment, diabetes mellitus, and possibly dyslipidemia supports the need to avoid antipsychotic polypharmacy.

It was noted that when prescribing two or more antipsychotics at the same time, most doctors do not take into account chlorpromazine equivalents, which becomes the most common cause of irrational therapy, and as a result, the neurotoxic effect of high and ultra-high total doses on integrative (frontal) functions, slowing down recovery processes, worsening the quality of remissions , the development of psychic and somato-neurological side effects.

At the same time, the cohort effect cannot be ruled out: the moral and psychological orientation of the individual to the standard of behavior characteristic of the social group to which he belongs (this implies lifestyle, non-compliance with diet and smoking, a lower level of education of patients). Data are considered mixed regarding weight gain, QT interval prolongation, and increased risk of mortality. There is a lack of convincing data regarding potential addictive properties and possible negative consequences such as tardive dyskinesia, neuroleptic malignant syndrome, agranulocytosis, sudden cardiac death, seizures and elevated liver enzymes.

It has been suggested that polypharmacy is associated with an increased risk of mentally ill mortality. According to the literature, it reaches twice the frequency compared with the general population and cannot be explained by an increased risk of suicide. Patients with schizophrenia are more likely to suffer from cardiovascular disease and diabetes. This is due both to lifestyle, diet, smoking, lower education, and antipsychotic therapy, causing, for example, QT interval prolongation and torsades de pointes ventricular tachycardia. It has been shown that the risk of death from cardiovascular pathology increases with an increase in the dose of an antipsychotic, regardless of its generation. However, in patients with schizophrenia who do not receive antipsychotics, mortality is 10 times higher than in those undergoing pharmacotherapy. The long-term effects of polypharmacy from this point of view are not well understood. There is evidence of an increased risk of death with increasing use of antipsychotics.

A study of cognitive deficit showed that it depends on the doses of drugs (risperidone and chlorpromazine equivalents), and not directly on the amount of drugs prescribed (doses of more than 5–6 mg of risperidone equivalents were associated with lower BACS results). It is important to note that with the combination of antipsychotic drugs, the prescribed doses often exceed the recommended ones.

Data on the adverse effects of antipsychotic polypharmacy are scarce and inconsistent. Most of the studies were either case-based or descriptive studies, often with small sample sizes and no control group. Some investigators have shown no effect or even improvement in patients with regard to side effects when treated with certain combinations of antipsychotics and/or after adding a second antipsychotic or reducing the dose of the first antipsychotic. For example, a combination of two antipsychotics with a reduced dose of the original drug may help normalize clozapine-treated glucose or prolactin levels and the severity of extrapyramidal disorders associated with risperidone therapy, while maintaining a sufficient level of blockade of dopamine transmission, and hence therapeutic efficacy. A number of studies have reported that augmentation of antipsychotic therapy with the second-generation antipsychotic aripiprazole results in a reduction in side effects such as sedation and drowsiness, hypersalivation, weight gain, dyslipidemia, hyperprolactinemia, and sexual dysfunction, probably due to its partial dopamine 2-receptor agonist properties. type . It remains unclear how the use of aripiprazole can contribute to weight loss and reduce the metabolic disorders associated with taking clozapine and olanzapine. Some studies have shown a positive effect on glucose levels by adding quetiapine to the treatment regimen while reducing the dose of clozapine, on the level of prolactin and extrapyramidal disorders - combining ziprasidone or low doses of haloperidol with low doses of risperidone. A study in which risperidone or ziprasidone were given in combination with clozapine showed that patients continued to gain weight and there were no significant differences in side effects. It is not known whether the effect of reducing adverse events will be observed when prescribing antipsychotics with a low risk of side effects when augmenting therapy with clozapine or olanzapine without dose reduction. The results of a meta-analysis indicate a positive effect of antipsychotic polypharmacy in the case of the use of clozapine.

The popularity of polypharmacy is explained by the fact that, unfortunately, in a third of patients it is not possible to achieve a complete response to antipsychotic therapy. The Schizophrenia Outcome Group's guidelines for psychopharmacotherapy indicate in their recommendations for augmentation strategies that many patients have an incomplete response to monotherapy. In these cases, polypharmacy is part of clozapine strategies. In clinical practice, in 60% of cases, clozapine is prescribed not as monotherapy, but in combination with other antipsychotics. Although basic scientific research suggests that clozapine augmentation with other antipsychotics results in greater binding of dopamine receptors, its effectiveness has not been sufficiently demonstrated in clinical studies. Much of the research is on the combination of clozapine and risperidone. The combination of risperidone with clozapine has been studied in randomized placebo-controlled trials. Only in one of them did the combination therapy significantly differ in its effect on the severity of psychopathological disorders. In general, studies of this combination of drugs have not demonstrated an adequate level of efficacy and safety for inclusion in recommendations for the treatment of patients with treatment-resistant schizophrenia. No difference from placebo in clozapine augmentation therapy was also shown for amisulpride and aripiprazole. Recent meta-analyses of clozapine augmentation and the efficacy of polypharmacy suggest that there may be little or no benefit from it. More evidence exists for antipsychotic augmentation with psychotropic drugs from other classes, such as mood stabilizers.

Several schemes discussed in the press based on the results of retrospective clinical observations can be cited as examples of the use of polypharmacy in clinical practice. Thus, the addition of thioridazine to risperidone or olanzapine in the initial period of therapy made it possible to stop anxiety and agitation. Other reports have reported positive experiences with the short-term addition of an antipsychotic to manage atypical manic symptoms following risperidone or olanzapine. In this case, it is impossible to judge whether this effect is a consequence of a pharmacological action or whether these are spontaneous phenomena within the framework of the dynamics of schizoaffective pathology. It does not discuss the possibility of switching to another atypical antipsychotic, adding a mood stabilizer, or optimizing the dosage of the original choice.

The combination of two or more typical neuroleptics in most cases is not indicated. There is little evidence to support the use of antipsychotic combinations if monotherapy has been effective. Although such drug combination strategies are widely used in clinical practice, they are outside the focus of guidelines for the diagnosis and treatment of schizophrenia.

Switching from antipsychotic polypharmacy to antipsychotic monotherapy has been considered in a very limited number of studies. In some of them, 50-67% of patients successfully tolerated such a correction of psychopharmacotherapy. There were no significant differences in the number of hospitalizations and severity of symptoms between the groups of patients who continued to receive two drugs and switched to monotherapy. The majority of patients from among those who underwent treatment correction in the future, after switching to monotherapy, returned to therapy with the original combination of drugs. At the same time, there is evidence that in cases of changing the attending physician in patients receiving more than one antipsychotic, psychiatrists are not inclined to transfer them to monotherapy.

It should be noted that in the domestic standards for the treatment of schizophrenia there are no recommendations on the number of prescribed drugs, only recommended doses of antipsychotics are given. There are indications for the use of combination therapy of clozapine with another second-generation antipsychotic (preferably amisulpride [Evidence level C], risperidone [C], aripiprazole [D]) in treatment-resistant schizophrenia, which may have advantages over monotherapy.

According to Russian experts, the national standards of antipsychotic therapy should establish certain restrictions regarding the dosing of drugs and the use of polypharmacy; the recommended dose ranges of classical antipsychotics should be revised downwards, and potentiation of the sedative effect, if necessary, should preferably be achieved by combinations of antipsychotic drugs with psychotropic drugs of other classes (for example, with mood stabilizers and / or anxiolytics).

Overall, the results of a systematic analysis of side effects associated with antipsychotic polypharmacy indicate that this area remains understudied. In addition, not all antipsychotic drug combinations are created equal. Antipsychotics are used to reduce the psychopathological symptoms and suffering of the patient and, ideally, to improve his quality of life and increase the level of social functioning. Because there is no evidence that antipsychotic polypharmacy is more effective than that seen with monotherapy, its use cannot be recommended.

Although many organizations and institutions have begun implementing policies to prevent the use of antipsychotic polypharmacy, there is little evidence to ban them in individual cases. There are currently insufficient data to assess the potential risks, benefits, and mediating outcome factors associated with antipsychotic polypharmacy.

It seems appropriate to recommend combination antipsychotic therapy in patients who have failed at least three courses of antipsychotic monotherapy, including clozapine. In other cases, the duration of polypharmacy should be based on clinical need: when changing therapy or when overcoming therapeutic resistance. It is important to bear in mind that most patients undergoing combination antipsychotic therapy are able to switch to antipsychotic monotherapy.

Guidelines for eliminating suboptimal prescribing practices, based on the Maudsley (2001) guidelines for prescribing, indicate that polypharmacy, i.e., the use of two substances of the same class, should be avoided unless there is either a database supporting this practice (e.g. a combination of mood stabilizers) or evidence of specific benefit to the patient.

Thus, we can state a gap between the results of evidence-based medicine and the actual daily practice of a doctor in relation to combination therapy with antipsychotics. Most psychiatrists use polypharmacy, however, it should be borne in mind that sequential switching from one antipsychotic drug to another may be more effective than combination therapy, and combination therapy with antipsychotics may be one way to overcome treatment-resistant conditions. It may be preferable to add small doses of antipsychotics to second-generation antipsychotics 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.Ketersburg, 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. The results of the research 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 patients undergoing a course of combined antipsychotic medication can safely transfer to antipsychotic monotherapy, thereby reducing the cost of treatment and increasing compliance.

KEY WORDS: schizophrenia, antipsychotics, polypharmacy.

CONTACT: [email protected]