RU2495685C1 - Method of choosing therapeutic approach to psychopharmacotherapy resistant schizophrenia - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely psychiatry, and may be used for choosing a therapeutic approach to psychopharmacotherapy resistant schizophrenia. For this purpose, after pharmacoresistance has been stated, total blood serotonine and daily dopamine excretion are examined. If observing the reduction of serotonin and standard or low dopamine excretion, a course of electric electroconvulsive therapy is applied. High dopamine excretion regardless of the serotonin content, a course of electric electroconvulsive therapy is applied. In the other cases, family psychotherapy is used. The patient is treated with underlying supporting psychopharmacotherapy. At the same time, electric electroconvulsive and insulin-comatose therapy is contraindicated in case of active, decompensated physical and neurological diseases.

EFFECT: method provides the higher clinical effectiveness in the treatment-resistant patients with individual pathogenic direction of the therapeutic effect.

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Description

The invention relates to medicine, namely to psychiatry, and can be used in the treatment of patients suffering from schizophrenia.

The high prevalence of schizophrenia is known: up to 45 million patients in the world (A. Tiganov, 2005). In terms of the world's population (5.8 billion), this is 0.77%. The data given are close to the index given by W.T. Carpenter and R.W. Buchanan (1995). They indicate that the prevalence of schizophrenia is characterized by 0.85%, i.e. approximately 1% of the world's population suffers from this disease.

In recent decades, psychopharmacotherapy has dominated the treatment of mental disorders. However, despite the emergence of a large number of new drugs and significant progress in understanding the mechanisms of action of psychotropic drugs, the number of therapeutically resistant (not sensitive to ongoing drug therapy) patients does not decrease and stably amounts to about 30% (Mosolov S.N., 2002,) . According to Brenner et al. (1990), Zelenina E.V. (2002), among patients with schizophrenia, the proportion of patients insensitive to treatment is 20-33%. In addition, in 60% of patients, an exacerbation of the disease is noted already a year after the course of active therapy.

Thus, the problem of resistance has become an everyday reality of medical practice; the doctor has to constantly look for ways and means to overcome it.

The well-known "Method of overcoming the pharmacoresistance of endogenous mental disorders" (Bukhanovsky A.O. et al. Pharmacoresistance in the treatment of endogenous mental disorders and methods for overcoming it. Scientific and methodical publication. Rostov-on-Don, 2007, 112 pp.).

The essence of the method is insulinocomatous therapy (ICT). Every morning, a patient develops a state of hypoglycemia by subcutaneous administration of insulin. The initial dose of insulin is usually 4-8 units. The stage of dose selection is that, depending on individual sensitivity to insulin, the daily dose is increased by 4-8 units to achieve grade 3 hypoglycemia (stupor). Subsequently, it is precisely the dose at which the soporotic state developed. The course of treatment consists of 15-25 procedures in which the state of stupor is achieved. ICTs are terminated simultaneously.

The duration of soporous conditions is 10-15 minutes. Relief of hypoglycemia is aimed at restoring blood sugar. 40% glucose in the amount of 40-60 ml is injected intravenously, if the dose of insulin does not exceed 100 PIECES, and 60-80 ml of glucose at a higher dose of insulin. As the consciousness clears up to 1-11 degrees, when the patient regains the ability to swallow on his own, sugar syrup is given (prepared by boiling a sugar solution) containing 150-200 g of sugar and a breakfast rich in carbohydrates.

The disadvantages of the described method include the lack of an algorithm for choosing this method of therapy and information about its effectiveness.

The well-known "Method for the treatment of pharmacoresistant schizophrenia using electroconvulsive therapy" (Nelson AI Electroconvulsive therapy in psychiatry, narcology and neurology /. - M: BINOM. Laboratory of knowledge, 2005, 368 S.).

Before electroconvulsive therapy (ECT), to reduce the risk of complications, each patient undergoes a number of mandatory studies: clinical blood and urine tests, ECG, chest x-ray, examination by a dentist, medical advice, oculist to exclude glaucoma.

ECT is performed under general anesthesia (non-inhalation short-term shallow mononarcosis) using muscle relaxants. The main task of anesthesia is to turn off the consciousness at the moment the current begins, followed by the quickest possible exit from anesthesia. At the same time, the patient’s fear of this treatment is mitigated, and choking associated with the use of muscle relaxants is also reduced. The most commonly used drugs for short-term anesthesia are sombrevin, thiopental sodium, hexenal, and ketamine. At the onset of narcotic sleep, a short-acting muscle relaxant is administered and an ECT session is performed. To record the duration of the seizure, a tourniquet is applied to the shoulder of the patient's arm, free from intravenous infusion, before the infusion of muscle relaxants. Muscle relaxants injected into a vein cannot penetrate distal to the tourniquet. Thus, this hand becomes a “control” - the neuromuscular block does not extend to the muscles of her forearm and hand, and they will be involved in convulsive activity during a seizure.

Artificial ventilation of the lungs (mechanical ventilation) is mandatory when conducting ECT with muscle relaxants, which helps to avoid a long delay in breathing.

Apply bilateral and unilateral ECT technique. As a rule, they use the initial frequency of sessions “in two days to a third”. When the patient's condition improves, the intervals increase. If the first 2-3 sessions did not cause positive dynamics, then the next 3-5 sessions are carried out at shortened intervals (up to 1 time per day), the application of electrodes (in the other hemisphere or bilaterally) is changed. The duration of the ECT course depends on the specific syndrome, as well as clinical changes during treatment and varies from 2-4 to 15-25 sessions.

The disadvantages of the described method include the lack of an algorithm for choosing this method of therapy and information about its effectiveness.

The well-known "Method for the treatment of schizophrenia" (Bukhanovsky A.O., Madorsky V.V., Soldatkin V.A., patent 2371209, Bull. ... No. 30 from 10.27.2009), including psychopharmacotherapy, psycho-educational classes, social skills training, different the fact that against the background of supporting psychopharmacotherapy, 8 stages of family psychotherapy are carried out. At stage 1, when a family calls for help, the psychotherapist discusses with family members the need for all family members to be present at family classes and follow all the psychotherapist's instructions; at stage 2, family members develop unified approaches to solving problems associated with ensuring the regularity of patients receiving the prescribed treatment and coping with family members with dangerous patient behavior; at the 3rd stage, the psychotherapist emphasizes that he is not a member of the family and cannot be the main one in it, the therapist provides an opportunity to choose the head of the family, and family members make this choice among themselves, achieving restoration of the family hierarchy; at the 4th stage, direct or paradoxical directives of the psychotherapist's prescriptions are developed; at the 5th stage, they control the requirements with the implementation of switching the attention of family members to pathological stereotypes of family interaction; at the 6th stage, the family is prepared for a possible relapse by the method of paradoxical prescription, with inducing subconscious resistance in the family members to exacerbation of the disease; at the 7th stage, relapse relief is performed, for which, during the relapse, family members themselves, calmly and confidently, with minimal consultative and psychotherapeutic help, using the knowledge acquired in the process of psycho-education, both medically and behaviorally, relieve the relapse; at the 8th stage, they switch to client-centered psychotherapy with the patient and, if necessary, members of his family.

The disadvantages of the method include the lack of clear biological criteria for choosing it as the main direction for overcoming pharmacoresistance.

We have not found any analogues of the method we use, which provide a clear choice of a specific method for the treatment of pharmacoresistant schizophrenia, based on an understanding of the pathogenetic mechanisms of suffering.

The aim of the invention is to increase the effectiveness of the treatment of pharmacoresistant schizophrenia.

This goal is achieved by the fact that after ascertaining the pharmacoresistance, studies of the level of total blood serotonin and daily excretion of dopamine are performed, if a decrease in the level of total serotonin and normative or decreased indicators of dopamine excretion are detected, in the absence of contraindications, the patient is offered a course of electroconvulsive therapy; if increased dopamine excretion is detected, regardless of the level of serotonin, in the absence of contraindications, the patient is offered insulinocomatosis therapy; in other cases, they offer family psychotherapeutic work. All proposed methods of treatment are carried out against the background of supportive psychopharmacotherapy. Contraindications for electroconvulsive and insulinocomatous therapy are actively ongoing, in the stage of decompensation somatic and neurological diseases.

The invention, “A Method for Choosing a Tactic for the Treatment of Schizophrenia Resistant to Psychopharmacotherapy,” is new, as it is unknown in the medical field in the treatment of resistant schizophrenia.

The novelty of the invention lies in the fact that for the first time a simple technique has been proposed that allows you to choose a specific counter-resistant tactics based on an understanding of the pathogenetic mechanisms of suffering. The essence of the technique is that by performing the proposed biochemical studies, the leading neurotransmitter disorder is detected (or its absence, which brings to the fore the need for family psychotherapy), and this allows you to choose the specific, most suitable treatment method. At the same time, the revealed predominant abnormalities in serotonin neuromediation are the basis for choosing ECT, because a certain tropism of this method to affective symptoms is known, and the dominant disorders in the catecholamine system (dopamine, in particular) suggest the choice of ICT.

The invention, “A Method for Choosing a Tactic for the Treatment of Schizophrenia Resistant to Psychopharmacotherapy,” is industrially applicable, as it can be used in healthcare, and medical institutions with a psychiatric profile.

"A method of choosing a treatment tactics for schizophrenia resistant to psychopharmacotherapy" is as follows.

When stating the pharmacoresistance, i.e. the patient's insensitivity to adequately conducted (in the proper doses and duration) psychopharmacological treatment, studies of the level of total blood serotonin and daily dopamine excretion are performed. According to the research 3 options are possible:

1. if a decrease in the level of total serotonin and normative or reduced indicators of dopamine excretion are detected, in the absence of contraindications (actively ongoing, somatic and neurological diseases in the decompensation stage), the patient is offered a course of electroconvulsive therapy;

2. if there is an increased excretion of dopamine, regardless of the level of serotonin, in the absence of contraindications (actively ongoing, somatic and neurological diseases in the decompensation stage), the patient is offered insulinocomatous therapy;

3. in other cases, they offer family psychotherapeutic work.

All proposed methods of treatment are carried out against the background of supportive psychopharmacotherapy.

1. ECT is performed under general anesthesia with muscle relaxants. Before the course, to reduce the risk of complications, each patient undergoes a number of mandatory studies: clinical blood and urine tests, ECG, chest fluorography, consultations of a physician, oculist to exclude glaucoma.

For short-term anesthesia, thiopental sodium is used. At the onset of narcotic sleep, a short-acting muscle relaxant (dithilin) is administered and an ECT session is performed. To record the duration of the seizure, a tourniquet is applied to the shoulder of the patient's arm, free from intravenous infusion, before the infusion of muscle relaxants. This hand becomes a “control” - the neuromuscular block does not extend to the muscles of her forearm and hand, and they will be involved in convulsive activity during a seizure. Mechanical ventilation (mechanical ventilation) is mandatory during the procedure.

Apply bilateral ECT technique. As a rule, they use the initial frequency of sessions “in two days to a third”. When the patient's condition improves, the intervals increase. The duration of the ECT course depends on the specific syndrome, as well as clinical changes during treatment and ranges from 2-4 to 15-25 sessions.

2. ICT is carried out as follows. Before starting treatment, an additional examination is carried out aimed at eliminating possible contraindications, which include actively ongoing, somatic and neurological diseases in the stage of decompensation. An ECG and an analysis of blood glucose levels are mandatory. Patients are consulted by a therapist, neurologist, optometrist. In the absence of contraindications, they begin to implement the method against the background of continued psychopharmacotherapy.

Every morning, a patient develops a state of hypoglycemia by subcutaneous administration of insulin; immediately after injection, 20 mg of anaprilin is given sublingually. The initial dose of insulin is usually 4-8 units. The stage of dose selection is that, depending on individual sensitivity to insulin, the daily dose is increased by 4-8 units to achieve grade 3 hypoglycemia (stupor). Subsequently, the exact dose at which the soporotic state developed (the insulin dose plateau stage) is used. The response to insulin administration is assessed by a hypoglycemic clinic. Its dynamics are staged (M.Ya. Sereysky, N.N. Zak) and is generally accepted among psychiatrists.

The course of treatment consists of 15-25 procedures in which the state of stupor is achieved. ICTs are terminated simultaneously.

The duration of soporous conditions is 10-15 minutes. Relief of hypoglycemia is aimed at restoring blood sugar. It is assumed that 1 U of insulin breaks down an average of 4 g of glucose. At the same time, 40% glucose in the amount of 40-60 ml is injected intravenously, if the dose of insulin exceeds 100 units, and 60-80 ml of glucose at a higher dose of insulin. As consciousness clears up to I-II degree, when the patient regains the ability to swallow on his own, sugar syrup is given (prepared by boiling a sugar solution) containing 150-200 g of sugar and a breakfast rich in carbohydrates.

3. Psychotherapy is carried out in the following way. Psychotherapy is carried out against the background of psychopharmacological treatment, psycho-educational activities, social skills training. It aims to correct the pathological stereotypes of communication in the patient's family due to the dosed reinforcement of the family crisis, which makes these changes inevitable, and the development of problem-solving behavior skills. Psychotherapy is carried out in 8 stages:

1. The struggle for family structure and initiative. It starts from the moment the family calls for help and aims to ensure that all family members are present at family classes and that they comply with all instructions of the psychiatrist and psychotherapist. Thus, overcoming the split and the formation of coalitions, typical for family members of schizophrenic patients, a crisis of family relations is initiated.

2. The development by family members of common goals and ways to achieve them. A survey is conducted of all family members about how they see family problems (including mental illness of a relative) and how to solve them. Unified approaches to solving problems are being developed, including mandatory measures to ensure the regularity of patients receiving the prescribed treatment, to control the socially dangerous behavior of the patient by the members of the family, and to ensure that he is restored to work or school after stopping the acute condition. The specific responsibility of various family members for the implementation of these agreements and the consequences of violation of their obligations by them is determined. It serves to strengthen the intra-family crisis by counteracting clear agreements and responsibilities that are characteristic of family members of patients with schizophrenia.

3. Detachment of the therapist from the family with the transfer of the initiative to its members. The therapist emphasizes that he is not a member of the family and cannot be the main one in it, raising the question of which member of the family will be the head and striving for the restoration of the family hierarchy with the mandatory establishment of the principle of unity of command in family relations, the responsibility of the head of the family for the result of treatment and clear fulfillment by all other family members of the instructions of the chapter regarding treatment of the patient. It serves to strengthen the intra-family crisis by counteracting the confusion of hierarchical relationships in the family, characteristic of family members of patients with schizophrenia.

4. The development of directives (direct or paradoxical prescriptions of a psychotherapist, including tasks for all family members aimed at correcting pathological stereotypes of family communication). It continues to intensify the intra-family crisis due to the fact that previous stereotypes of intra-family interaction become impossible.

5. Monitoring compliance with the requirements of focusing the attention of family members on pathological stereotypes of family interaction with the transfer of attention from the patient's problems to the problems of other family members and methods for solving them. Opposes the conviction typical for families of schizophrenic patients that all problems are only a consequence of the patient’s illness and creates the conditions for the beginning of the assimilation of new, more effective rules for intra-family interaction.

6. Preparing the family for a possible relapse using the paradoxical principle of relapse. In an effort to provoke a subconscious backward reaction from the patient and his family members with the help of a paradoxical prescription, the therapist insists that this disease is sure to relapse, moreover, it is necessary, since only during relapse family members will be able to check how effective previously developed measures to combat the disease and, accordingly, the sooner a relapse occurs, the better to improve the quality of work. This not only reduces the chances of developing relapse due to subconscious resistance of family members to the implementation of this “prescription”, but also makes it easier to cope with the reactions of fear and despair familiar to the patient and family members, if relapse does occur, creates the conditions for its quick and effective relief on an outpatient basis with minimal social maladaptation of the patient.

7. Relief of relapse. The members of the medical team strive to ensure that family members themselves, calmly and confidently, with minimal counseling and psychotherapeutic help, based on the knowledge acquired in the process of psychoeducation, both medicinally and behaviorally, if possible, without hospitalizing the patient, are able to cope with the exacerbation .

8. The transition to client-centered psychotherapy with the patient and, if necessary, members of his family, carried out against the backdrop of periodic joint meetings of the whole family and ongoing supportive psychopharmacotherapy.

An example of a specific application of the “Method of choosing tactics for the treatment of schizophrenia resistant to psychopharmacotherapy” in patients.

Patient K.A.B., 18 years old, medical history 56/05.

From the anamnesis: heredity is aggravated by alcohol abuse by the father, schizophrenia by the mother.

The patient was born 5.2.87 from the first, non-pathological, pregnancy, first birth. Mother 22 g. For childbirth. Born with a weight of 3350 g, height 53 cm, mature, full-term, screamed immediately.

He did not lag behind in growth and development, doctors did not find any pathologies during examinations. Attention was expressed by pronounced tearfulness, poor night sleep and prolonged preservation of enuresis (up to 5 years).

From the age of 1.5, he visited a day nursery, not too willingly (although he did not act up there, he was kind, sociable, other children were drawn to him). I could not fall asleep at lunchtime, he was sent to play in another room.

Home education - in the style of an indulgent hyper-custody ("trembling over him"). When the patient was 1 year 7 months old, a sister was born; did not show jealousy.

At the age of three, he was transferred from a day nursery to the garden and adapted easily. Willingly talked with children, in the evening for a long walk with peers in the yard. In preschool age he was "somewhat hooligan, mobile, active, sociable, responsive, affectionate."

I went to school at the age of 7 (1994), being able to read and write, which compares favorably with other children. Easily won the favor of classmates and teachers (despite the always present “inclination to fight”). He studied well and excellently until the 7th grade, giving preference to humanitarian subjects (especially English).

In the 7th grade (14 years), academic performance declined. Often I missed classes, spent a lot of time in the company of peers, and started smoking tobacco. With the elders he remained friendly, benevolent, synthonic; teachers noted good abilities, but lack of desire to learn. In the 9th grade (16 years), on the initiative of his parents, he moved to another school ("with the goal of separation from a bad company, but she overtook him there too ..."). The hobby reactions of this period are sports and religious (questions of faith always attracted him, and together with all his peers he studied the Koran, tried to follow the commandments, which, however, was far from constant). The basement of the parental home was converted for his needs - he studied there, installed sports equipment, and performed llamas there. Its basement has always been a meeting place for a large youth company.

In 2004 (17 years old) he graduated from high school and entered the university at the Faculty of Philology. I liked studying at the university, I was engaged in it with pleasure, the head of the group was chosen.

Parents began to notice the first changes in the patient’s condition in October 2004: he unexpectedly began to say that “his comrades who came in the evenings interfered with him”, began to avoid talking to them, and outwardly in the group he talked easily and freely. He began to spend more time in his basement, while his parents often found that the patient was too late; sometimes he slept for several hours a night, slept on weekends. Parents did not notice a noticeable change in mood and all changes were associated with high workloads at the university. In January 2005, he successfully passed the session; to its end looked exhausted. At the beginning of January, he "fell ill: did not get out of bed, refused to eat." In conversations with his parents, he asked for help, "to cure him." On February 15, 2005 he was hospitalized in the therapeutic department, where he was diagnosed with “hr. cholecystitis, exacerbation, hr. pancreatitis, exacerbation. Astheno-neurotic syndrome. " He refused droppers in the department, avoided communication; behavior has become unusual. So, during prayer he did not observe the prescribed ritual, sometimes he answered inappropriately, it is not clear. At the initiative of the mother was consulted by a psychiatrist. The patient did not open up in experiences; dynamic observation was recommended. On 22.2.05, the patient unexpectedly accepted 20 tablets. phenazepam, explaining that it was intended to "calm down"; the duty shift carried out a gastric lavage, detoxification was performed. February 23 was discharged, according to the description, in a state of medical confusion. He expressed a lot of ridiculous ideas. He first reported that he “hears voices, in particular of Allah and Iblis,” “a voice forbids him to eat.” He said that "in paradise he has a wife, three children, and if he eats, they will starve." He said that "the voice directs him, makes him commit actions aimed at purification." For this, in particular, it was necessary to “cut off his hand and eat it”, which the patient tried to do by stabbing his fingers with a knife. He said that "worms destroyed his liver and kidneys." Constantly listened.

At the beginning of March 2005, she was again consulted by a psychiatrist. Assigned haloperidol 10 mg / day, cyclodol. His condition improved somewhat: the patient became calmer, expressed delusional ideas less often, stopped “falling to his knees and praying at every corner”. 5.4.05 was hospitalized in a psychiatric hospital.

Somatic status. Normostenik, low nutrition. The skin and visible mucous membranes of normal color. Cut wound of the brush in the healing stage. Peripheral lymph nodes are not enlarged. Heart tones - clear, rhythmic. In the lungs with auscultation - vesicular breathing. The tongue is moist, slightly coated with a white coating. The abdomen is soft, painless. Liver at the edge of the costal arch, painless on palpation. The edge is smooth. The spleen is not palpable. Pasternatsky’s symptom is negative on 2 sides.

Neurological status. In the classic and sensitized Romberg test is stable. The palatine test performs accurately. There is no tremor. Tendon reflexes are lively, symmetrical. There are no pathological reflexes and sensory disturbances.

Mental status. Consciousness is formally clear, correctly oriented in the place and self, the orientation in time is fuzzy. He comes to conversations willingly, strives for communication. Keeps free, at the same time sintonen, polite. Facial expressions and pantomimics live. The voice is emotional, well modulated; Speech at a fast pace.

Talks about “voices that sound inside his head. The voices belong to Allah and Iblis. ” "Allah tells what needs to be done to be cleansed, he narrates about the structure of the Universe." Sometimes voices are supplemented by visions - they arise "inside the head, less often in the surrounding space."

Independently draws attention to the inconsistency of the "information" provided to him, but is inclined to see this as confirmation that "evil forces communicate with him, not Allah"; formally agrees with the suggestion that voices may indicate the presence of a mental disorder. In any case, "I would like to get rid of it and be like everyone else."

He talks about his subordination to “someone else’s will”: “they force me to remember, sometimes they inspire other people's thoughts, they literally forced me to kneel down several times”.

He believes that everything that happens to him is due to the fact that he "is elected, is a prophet." He "has already completed several miracles."

The criticism is superficial and formal.

The conclusion of the psychologist. The study reveals signs of a schizophrenic symptom complex (impaired thinking in the form of slippage on non-essential signs).

The results of additional studies.

- MRI GM 15.4.05. Signs of the initial manifestations of encephalopathy.

- Total blood serotonin (04.16.04.): 0.52 μmol \ l (normal 0.45-

0.77 μmol \ l).

- Daily excretion of dopamine (04.16.04): 1232 nmol / day (normal 900-1050 nmol / day)

- REG 6.4.05. Pulse blood filling within normal limits in both pools, venous outflow difficult, more on the right.

- EEG 6.4.05. Mild diffuse changes in bioelectric activity by organic type. Mild signs of trunk dysfunction.

- Prolactin 6.4.05. 4.07

- Thyroid hormones 6.4.05. - within the normal range.

- Circulating immune complexes 7.4.05 - 70 conventional units

- Blood lithium 04/06/05. Less than 0.2 meq \ l.

- Markers of viral hepatitis 12.4.05 - neg.

- General blood tests, urine tests; blood biochemistry 6.4.05 - normal.

Expert advice:

- Neuropathologist. 04/15/05. Signs of focal CNS lesion were not detected.

9.4.05 a consultation was held consisting of: prof., MD Bukhanovsky A.O., attending physician MD Soldatkin V.A .. Diagnosis: F 20.01 Paranoid schizophrenia, type of episodic course with an increasing defect.

The treatment was carried out:

Ziprex was chosen as the base drug (up to 30 mg per day), however, the phenomena of negative resistance (marked side effects) were noted. He received Rispolept therapy (up to 8 mg / day), with insignificant positive dynamics.

Considering the phenomena of pharmacoresistance, and taking into account the obtained paraclinical data (increased daily dopamine excretion), insulin therapy was chosen by the method of termination of the attack of the disease. Fulfilled 20 soporotic conditions. The attack is completely stopped, the patient was discharged in a state of high-quality remission, with full criticism of the transferred psychosis.

Follow-up: 7 years. The condition remains good. The patient graduated with honors from the university, works.

The proposed method treated 67 patients suffering from schizophrenia, with signs of pharmacoresistance.

Follow-up monitoring of patients who received care was performed in the period from 6 months to 10 years. Persistent remission was achieved in 25 (37.3%) cases, a noticeable improvement was observed in 33 (49.3%) patients. Therapy was ineffective in 9 (13.4%) patients.

The technical and economic efficiency of the “Method for the selection of tactics for the treatment of schizophrenia resistant to psychopharmacotherapy” lies in the fact that the use of the method can significantly increase the effectiveness of therapeutic and preventive measures, giving them a pathogenetic focus.

Claims (1)

A method for choosing a tactic for the treatment of schizophrenia resident to psychopharmacotherapy, including psychopharmacotherapy, insulinocomatous, electroconvulsive therapy and family psychotherapy, characterized in that after ascertaining the pharmacoresistance, studies of the level of total serotonin and daily excretion of dopamine, when detecting a decrease in the level of seroton or a decrease in the level of seroton dopamine excretion the patient is offered a course of electroconvulsive therapy; when detecting increased excretion of dopamine, regardless of the level of serotonin, the patient is offered insulinocomatous therapy; in other cases, they offer family psychotherapeutic work; all proposed treatment methods are carried out against the background of supportive psychopharmacotherapy; contraindications for electroconvulsive and insulinocomatous therapy are actively ongoing, in the stage of decompensation somatic and neurological diseases.