RU2447832C1 - Method for prediction of risk of delayed dyskinesia accompanying neuroleptic therapy in schizophrenics - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, more specifically to psychiatry, and may be used for prediction of the risk of delayed dyskinesia accompanying schizophrenia treatment. Schizophrenic's blood serum is examined to determine the following biological values: pre-treatment amount and relation of reduced and oxidised glutathiones. The low amount of reduced glutathione (108 mcg/ml) and the reduced to oxidised glutathione ratio index lower than 0.49 provides predicting the high risk of delayed dyskinesia in schizophrenics with underlying neuroleptic therapy.

EFFECT: method provides the pre-treatment prediction of the risk of delayed dyskinesia that enables choosing an individual therapeutic approach.

1 tbl, 2 ex

Description

The invention relates to medicine, specifically to psychiatry, and can be used to predict the risk of developing tardive dyskinesia in patients with schizophrenia that develops when taking antipsychotics.

The problem of side effects of antipsychotics has important social significance due to the fact that in Russia about 70-80% of schizophrenic patients receive therapy with traditional antipsychotics, which often lead to the development of motor disorders. Late (tardic) antipsychotic dyskinesia is understood as any hyperkinesis if it satisfies two main criteria: firstly, it arises as a result of long-term use of antipsychotics, and secondly, it persists after drug withdrawal [1]. Tardive dyskinesia is a serious side effect of prolonged antipsychotic therapy in patients with schizophrenia and develops in 20-30% of patients receiving antipsychotics [2]. Late dyskinesia is caused by traditional antipsychotics that block D2 receptors (haloperidol, chlorprotixen, chlorpromazine, trifluoperazin, etc.) [3]. This side effect is generally not characteristic of atypical antipsychotics, with the exception of risperidone, which also has an affinity for D2 receptors.

Currently, there are no reliable predictors of the risk of developing tardive dyskinesia (PD) with antipsychotics. Given the high economic costs due to the duration of the use of antipsychotics and the facts that tardive dyskinesia significantly worsens the quality of life of patients and is often the reason for refusal to take antipsychotics, it is necessary to search for criteria for predicting the risk of dyskinesia.

An adequate prototype of the proposed invention, which allows before treatment to determine the risk of developing tardive dyskinesia in patients with schizophrenia, was not found in the analyzed literature.

The objective of the invention is to determine the risk of developing tardive dyskinesia in patients with schizophrenia before starting antipsychotic therapy.

The task is achieved by determining the biological parameters in the blood serum of patients with schizophrenia: the amount of restored glutathione and the ratio of restored glutathione to oxidized in patients before treatment. At low values of reduced glutathione (below 108 μg / ml) and low values of the index of the ratio of reduced glutathione to oxidized (below 0.49), a high risk of developing tardive dyskinesia in schizophrenia patients is predicted under the influence of antipsychotic therapy.

New in the proposed method is the use of the amount of reduced glutathione and the index of the ratio of reduced glutathione to oxidized to predict the risk of developing tardive dyskinesia in patients with schizophrenia, under the influence of antipsychotic therapy.

A study of the amount of reduced glutathione and the index of the ratio of reduced glutathione to oxidized to predict the risk of developing tardive dyskinesia was chosen because, according to the literature, an important role in the pathogenesis of tardive dyskinesia is played by oxidative stress and impaired antioxidant defense [4, 5]. The glutathione system (reduced and oxidized glutathione and their ratio) reflects the redox potential of the cell and is an important link in the implementation of antioxidant protection.

Distinctive features showed in the claimed combination of new properties that are not explicitly derived from the prior art in this field and are not obvious to a specialist. An identical set of features was not found in the patent and medical literature. This method can be used in healthcare for the application of individual therapeutic tactics.

Based on the foregoing, the present invention should be considered appropriate to the conditions of patentability: "novelty", "inventive step", "industrial applicability".

The invention will be clear from the following description.

The proposed criteria (low values of the amount of reduced glutathione and a decrease in the numerical index of the ratio of reduced glutathione to oxidized) of the risk of developing tardive dyskinesia were obtained as a result of a clinical and biological examination of patients with an established diagnosis of schizophrenia who underwent treatment in the Department of Endogenous Disorders of Clinics Research Institute of Mental Health SB RAMS.

23 patients with a diagnosis of paranoid schizophrenia were examined. Psychopathological symptoms were described according to the Guideline “Symptom Assessment List and Glossary for Mental Disorders” for ICD-10. Each patient, upon admission to the clinic before the appointment of pharmacotherapy and after 6 weeks of pharmacotherapy, was examined on the AIMS scale (assessment of pathological unintentional movements). As antipsychotic therapy, patients received the following drugs in the form of monotherapy or their combinations: traditional antipsychotics - haloperidol in doses of 10-30 mg / day, chlorprotixen in doses of 100-200 mg / day, chlorpromazine in doses of 100-200 mg / day, trifluoperazin doses of 20-40 mg / day, thioproperazine 5-20 mg / day, clopixol in doses of 40-80 mg / day; atypical antipsychotic - risperidone in doses of 4-6 mg / day.

The Pathological Unintentional Movement Scale (AIMS), which is used to assess tardive dyskinesia [6], consists of seven main scales: mimic movements of the face and mouth area (facial muscles, for example, forehead, eyebrow, eye area, cheeks, including eyebrow movement, blinking eyes, a smile, grimaces; lips and the area around the eyes - for example, when the patient frowns, puffs his lips, smokes: jaw - for example, when the patient bites, clenches his teeth, chews, opens his mouth, does lateral movements of the jaws; tongue, for example, about enit only strengthen the movement of language); 5 - movements of the upper limbs (shoulders, arms, hands, fingers), including choreal movements (for example, fast, objectively useless, random, spontaneous); athetoid movements (e.g. slow, erratic, complex, writhing); 6 - lower extremities (legs, knees, ankles, toes), for example, lateral movements of the knees, tapping the foot, heel kicks, wriggling foot movements, rearrangement of the feet; 7 - body movement (neck, shoulders, hips), for example, wriggling, swinging, turning movements, rotation of the pelvis in a circle.

The degree of severity on each scale is estimated from 0 to 4: 0 - absent, 1 - minimally expressed, 2 - poorly expressed, 3 - moderate, 4 - strongly expressed. The diagnosis of tardive dyskinesia is made in international practice using two different criteria - the patient has mild disorders (2) on two scales or moderate disorders (3) on one scale (Schooler and Kane criterion) or a more common criterion is the presence of mild disorders (2) on one scale [7, 8, 9]. In our studies, we used the second criterion.

After six weeks of therapy, the studied group of patients based on the AIMS score was divided into two groups: with signs of tardive dyskinesia and without signs. 7 patients showed signs of tardive dyskinesia developed as a result of treatment (3 men and 4 women; age range from 25 to 50 years, average age 32.6 ± 5.75 years; average disease duration 5.78 ± 3, 72 years). The group of patients with schizophrenia without signs of tardive dyskinesia was 16 people, including 7 men and 9 women. The age range was from 20 to 47 years, the average age was 30.9 ± 3.78 years, and the average duration of the disease was 5.19 ± 2.88 years.

At the examined persons, upon admission to the clinic before the appointment of pharmacotherapy, a laboratory examination was carried out. Blood was taken on an empty stomach in the morning using Vacuette tubes. Venous blood was centrifuged to obtain serum at 1,500 rpm for 20 minutes. Blood serum was aliquoted and stored in a freezer at -70 ° C until analysis.

The method for determining the concentration of reduced glutathione is based on the formation of a fluorescent complex of glutathione with orthophthalaldehyde [10].

Description of the technique. To determine the concentration of glutathione, 600 μl of blood serum was taken, 200 μl of metaphosphoric acid and 300 μl of 0.1 M phosphate buffer (pH 8.0) with 5 mM EDTA were added. Centrifugation was carried out at 1500 rpm at 4 ° C.

To determine the concentration of reduced glutathione, 2.25 ml of 0.1 M phosphate buffer (pH 8.0) with 5 mM EDTA was added to 250 μl of the obtained supernatant. Then, 100 μl of the resulting solution was taken, 1.8 ml of 0.1 M phosphate buffer (pH 8.0) with 5 mM EDTA and 100 μl of orthophthalic aldehyde (OFA) prepared at the rate of 8 mg of OFA per 2 ml of ethanol were added. Incubated for 15 minutes at room temperature. The optical density was measured on a Varion spectrofluorimeter at Em (emission wavelength) of 420 nm and Ex (excitation wavelength) of 350 nm.

To determine the concentration of oxidized glutathione, 100 μl of N-ethylmolyemide was added to 250 μl of supernatant at the rate of 10 mg of N-ethylmolyemide per 2 ml of distilled water. Incubated for 30 minutes at room temperature, after which 2.15 ml of 0.1 N was added to all tubes. NaOH. Then, 100 μl of the resulting solution was taken, 1.8 ml of 0.1 N was added. NaOH and 100 μl OFA. Incubated for 15 minutes at room temperature. The optical density was measured on a spectrofluorimeter with Em (emission wavelength) equal to 420 nm and Ex (excitation wavelength) equal to 350 nm. Results are reported in μg glutathione per 1 ml of serum.

According to the results of assessing the amount of restored glutathione in patients with schizophrenia between the group of patients with advanced tardive dyskinesia and patients without it, significant differences were obtained with p = 0.0123. A characteristic feature of the group of patients with tardive dyskinesia is a significant decrease in the amount of restored glutathione in the blood serum.

The difference between the groups in the numerical value of the index of the ratio of the amount of reduced glutathione to oxidized was revealed. In patients with developed tardive dyskinesia, this ratio has a lower value (Table 1).

Table 1 The amount of reduced and oxidized glutathione and the index of the ratio of the amount of reduced (GSH) to oxidized (GSSG) in the blood serum of patients with schizophrenia, depending on the presence of tardive dyskinesia Indicators Schizophrenia patients without tardive dyskinesia with tardive dyskinesia Reconstituted Glutathione (μg / ml) 118.92 ± 5.617 101.52 ± 3.613 * P Oxidized Glutathione (μg / ml) 227.06 ± 11.13 231.9 ± 19.67 GSH / GSSG 0.52 ± 0.009 0.471 ± 0.011 * P Note. * P - the reliability of the level of differences in the results in groups.

A decrease in the amount of reduced glutathione in patients with schizophrenia reduces the ability of the cell to bind the excessive amount of free radicals involved in the pathogenesis of schizophrenia, and also reduces the ability of the cell to utilize xenobiotics. The index of the ratio of the amount of reduced glutathione to the oxidized one characterizes the redox potential of the cell - the higher its value, the higher the cell's regenerative capacity. A decrease in these indicators is unfavorable for humans and contributes to the development of tardive dyskinesia in patients. A decrease in the basic antioxidant parameters of the cell leads to an increased risk of dyskinesia in patients with schizophrenia.

Thus, the use of determining the amount of glutathione and the index of the ratio of its reduced and oxidized forms as additional paraclinical examination methods before prescribing therapy allows predicting the risk of developing tardive dyskinesia and using individual therapeutic tactics in patients.

Example 1 (patient without tardive dyskinesia). Case history No. 111. Patient T., born in 1984, sick 8 years old, disabled person of group II.

Anamnesis: Obstetric history without pathology, was born on time. In mental and physical development in early childhood, she did not lag behind her peers - she began to sit, walk and talk on time. Often suffered from colds, without complications. Approximately, at the age of 2 years she was given to kindergarten, where she easily adapted. From an early age, she was distinguished by some touchiness, moodiness, but she was sociable, easily converged with people, adapted to an unfamiliar environment, aspired to leadership among her peers, preferred outdoor games. At 7, she went to school, already knowing how to read. She studied in a gymnasium class, coped easily. At the same time, adaptation difficulties appeared among peers due to excessive desire for leadership, without taking into account the situation. She reacted negatively to any attempts to direct her; she considered the remarks “unfair”. At the age of 15, her beloved cat was lost, to which the patient was very attached. She was shocked, cried, then became lethargic, passive, did not talk to anyone and refused to eat for a week. The condition stopped spontaneously.

At the age of 16, she gradually began to refuse to watch her favorite TV shows for no apparent reason, stopped listening to the music she was fond of, and gave the tape recorder with audio tapes to her parents, saying that she no longer needed it. She stopped monitoring her appearance, did not clean the room, was not interested in anything, closed herself. Almost did not leave the house, stopped supporting relations with friends and classmates, actively avoided their invitations to go to the cinema or to a disco. Soon she stopped attending school, explaining this by fatigue, loss of interest, conflicts and insults with classmates, according to her parents, there were no objective conflicts at school. I passed the final exams with difficulty. Parents enrolled at Seversky Industrial College without examinations, but after a week she stopped attending it, finally closed up, practically stopped talking, spent all the time in bed, slept a lot, became apathetic and indifferent to everything. At the insistence of her parents, she was hospitalized in a planned manner in the psychiatric ward No. 2 of MSCh-81 in Seversk, where she stayed for 2 months with a diagnosis of Schizophrenia, simple form, simplex syndrome. Discharged from the department at the insistence of the parents. For 2 months I was at home. According to the parents, the first 2 days after discharge from the hospital, motor excitement was observed, constantly strove to go somewhere, was looking for something. During this period, when she was at home, she took tianeptine, piracetam, against this background, she sometimes began to watch television programs, but most of the time, as before, she spent in bed, showing no interest in anything. I answered monosyllabic questions, refused everything, a habit of stereotyping straightening my hair with my hand appeared. At the initiative of parents, they turned for help to the clinics of the research institute IZ TNC SB RAMS. She received treatment: risperidone 6 mg / day, piracetam 5 ml i / m No. 10, per os 800 mg / day, glutamine to 1 table. 3 times a day. As a result of treatment, she became somewhat more active, took care of herself, came into contact with other patients as necessary. At the same time, it remained uninitiated, ambivalent with a marked impoverishment of thinking and a decrease in energy potential. With a diagnosis of Schizophrenia, a simple form, was discharged from the department, a recommendation was made to continue taking risperidone 4 mg / day.

Within a month after discharge, there was an improvement, the patient washed herself, brushed her teeth, and after her parents' request she cleaned her room. At the end of September 2002 (after 6 months), parents were again hospitalized at the Research Institute of Mental Health. At admission, there was a lack of body weight. Motility is extremely peculiar: the gait is robotic, the movements of the hands when walking are not synchronized, uncoordinated, after a long sitting in a uniform pose made a series of unexpected sharp movements of the hands. Ears are sharply hyperemic, edematous, with bedsores. The expression on the face is indifferent, the facial expressions are poor, for periods it was inadequate smiling, stereotyped corrected greasy hair. Answered monosyllables. Sometimes she complained that her head was almost always “empty, no thoughts”, in a conversation it is difficult to concentrate on the words of the interlocutor, she loses her thought. She was not interested in anything; she was not burdened by her condition. Hallucinatory and delusional symptoms were not detected. After discharge, II disability group was issued, received treatment with flupentixol-depot. During the year she remained passive, was not interested in anything, performed hygiene procedures after persistent persuasion, rarely went for walks. In 2004, on the recommendation of a doctor, she switched to taking olanzapine 5 mg. However, after 4 months of treatment, the patient gained about 20 kg, and therefore was transferred to risperidone at a dose of 4 mg. It became a little more passive than when taking olanzapine, but in general the condition remained satisfactory. Weight gain slowed, but by 2006 the patient's body weight was 81 kg, which is 32 kg more than the original weight. To reduce appetite, fluoxetine 20 mg was added to the treatment regimen, but less than a month later the drug was canceled due to persistent nausea. In November 2007, she stopped taking antipsychotics, hid tablets behind her cheek and under her tongue, and then folded them on a table. The condition worsened, became irritable, sleep disturbed, began to refuse food, a lot of stereotypical movements appeared (scratched the skin of the face, pulled hair). After the discovery of the hidden tablets, she began to take the previously prescribed dose under the strict supervision of her parents, but her condition continued to worsen, she practically did not get out of bed, pressure sores appeared in the coccyx, and she lost a lot of weight. In this condition, she was taken to the clinics of the Research Institute of Pediatric Surgery SB RAMS, was hospitalized in January 2008 in the 2nd clinical unit.

Mental state at admission. He comes to the conversation only by invitation. Short cut hair, disheveled, unwashed. Does not use cosmetics, does not monitor the appearance. During the conversation, the posture is monotonous, the movements are individual, sharp, angular, stereotypically corrects the bangs, trying to remove short hair by the ear, periodically looks around, while the look is absent, hypomimic. He reluctantly enters into the conversation, spontaneous speech is absent, he answers the questions with a pause in monosyllables: yes, no, I don’t know, or with very simple short sentences. He does not actively complain, the patient does not consider himself, explains hospitalization with the desire of his parents to cure her, but does not understand what. During the conversation, it was possible to find out that in the head there is a constant feeling of emptiness, there are no feelings and interest in everything, he understands the abnormality of his condition, but does not want to do anything, since he does not bother with the state. Hallucinatory-paranoid symptoms, suicidal thoughts, poor mood denied. Mostly in the ward, she spends a day in bed, does not bother to stay, does not seek to go home, does not communicate with any of the patients or medical personnel. She does not take care of herself, she rinses and brushes her teeth under the control of the staff, despite numerous remarks about sleeping, she lays down in bed clothes in bed clothes without bedding. She is indifferent to the visits of her father or grandmother, on their initiative she goes to the street with them, but not for long, because she says that she is tired and wants to lie down.

Diagnosis. Simple schizophrenia, continuous course (F20.60). She received treatment with risperidone at a dose of 4 mg per day, against which she became calmer, her sleep returned to normal, but she remained uncommunicative, spent a lot of time lying in bed, and did not take care of herself. After 3 weeks of therapy, the antipsychotic thioproperazine 5 mg / day was added; it was possible to achieve a complete reduction in productive symptoms, it became more active, the number of stereotypical movements decreased, it was possible to heal pressure sores, began to get involved in internal labor processes, the appetite was restored, conversations lasting up to 5-7 minutes, collection of anamnestic information became possible.

In the course of the entire therapy, adverse motor disorders were not detected. The total score on AIMS scales was 0 points at admission and after 6 weeks.

Laboratory indicators at admission to the clinic: GSH (reduced glutathione) - 134.93 mcg / ml; GSSG (oxidized glutathione) - 244.81 μg / ml; GSH / GSSG (ratio) - 0.551.

Example 2 (patient with tardive dyskinesia).

Case history No. 838. Patient K., born in 1977, sick for 10 years, disabled person of group II.

Anamnesis. Heredity for schizophrenia is not burdened. He grew up a weak child, often suffered from colds, somewhat lagged behind his peers in development. He suffered chickenpox, scarlet fever, mumps in severe form. From a year and a half he attended preschool institutions, where teachers described him as the most closed, detached child. He suffered from enuresis until the age of 16, in connection with which he was registered with a neuropathologist. I went to school on time, studied mediocre with great efforts and help from my mother. In adolescence, became quick-tempered, irritable, did not tolerate objections and comments to him. Expressing dissatisfaction, he could break the dishes, the glass in the doors. Negativism was demonstrated only in the family circle, and in public remained closed, shy. After graduating from eight classes, he entered the Electromechanical College. He thinks he got sick around this time after overwork during preparation for exams. Relatives noticed that the patient became drowsy, inhibited, hardly woke up in the morning. He reacted violently to his mother’s calls to get up in the morning, screaming, clashing, banging his head against the wall in a fit of irritability. He became even more withdrawn, stopped attending classes, locked himself up in his room, ate nothing. The mood was dreary, the soul was empty. At the initiative of his mother, at 17, the patient was hospitalized in the Altai Psychiatric Hospital. Received trifluperazine, thioridazine, perphenazine, metophenazine. Diagnosis at discharge: Simple schizophrenia. Remained lethargic, lethargic, fenced off. He had no friends, practically did not communicate with anyone. All the time I spent at home. He wandered aimlessly around the apartment, lying, was not busy with anything, showed no interest in anything. He did not watch himself, was sloppy, did not wash, did not comb his hair. It took a lot of effort for his mother to get him washed. I didn’t change the linen myself. In general, he was calm, but sometimes unmotivated irritability arose. Suddenly becoming rude, cynical. He behaved ridiculously, unnaturally laughed. Could in response to the slightest remarks, and sometimes without reason, forcefully hit the mother in the face, on the head. At the age of 18, his condition worsened again - he became agitated, fussy, verbose, spoke without interruption, molested his mother with a wide variety of questions. He made ridiculous things, could suddenly tumble over, stand on his head. Irritability and temper intensified, she began to constantly beat her mother. He felt fears, said that it seemed to him as if someone was climbing out the window. Every day, aggressiveness and excitement intensified. He demanded money from his mother, while threatening her with physical harm. Suddenly he left for Novosibirsk. On the way, I lost my things, met random people, bought them alcohol. Returned after 2 days even more excited. After leaving the store, he got on a strange bike, was detained by police. After 2 days, on the initiative of his parents, he was hospitalized at the Institute of Mental Health SB RAMS. He was on treatment for about a month. The department was foolish, aggressive. Once I heard inside my head the voice of my father, who scolded the patient. In addition, pop songs sounded in my head. He received the same drugs as during the first hospitalization. Once I heard a voice in my head that ordered him to hang himself, but did not take any suicidal actions. Was discharged with improvement. He took the supportive treatment irregularly and after a month and a half he felt worse again. In the future, he again entered the Research Institute of Science and Technology of the Siberian Branch of the Russian Academy of Medical Sciences annually in connection with ridiculous and "foolish" behavior. As a result of treatment with thioproperazine, levomepromazine, clozapine, the state of health improved, behavior was ordered, but negativity, emotional-volitional disturbances, amorphousness, inconsistency of thinking remained, the second group of disability was formed. At home he continued to take the prescribed treatment, was observed in the dispensary. He remained inactive, passive. He lived with his mother and sister, who provided for his life. Against the background of treatment, the patient had a urination delay, in connection with which, on the initiative of his mother, he turned to the clinic of the Scientific Research Institute of Pediatric Medicine SB RAMS, where he was hospitalized.

Mental state at admission. Outwardly untidy, messy. Dressed in a crumpled shirt, dirty sweatpants. Hair is not washed, unkempt for a long time. Gait slow, shuffling. Looks younger than his age. Facial expression is naive-silly. The movements are angular, constrained. Emotional manifestations are scanty, inexpressive and inadequate to the situation: the patient is sometimes gloomy, then smiles for no reason. Gestures are unmotivated, unexpected, can not find a place for hands, then iterates over their clothes, then rubs or squeezes them, covers his face, scratches his head. The speech is monotonous, quiet, monotonous. It is passive, during the conversation it remains indifferent, indifferent, answers questions after a long pause, briefly and monosyllabic “yes” or “no”. Thinking is poor, meager in content, divorced from reality. Repeats phrases spoken by a doctor. Statements are stereotyped, fragmented. Disorders of perception and the presence of delirium denies. Attention is scattered, unstable, can not concentrate. There is no criticism of his condition. He is invisible, closed, walks hunched over, prefers not to leave the ward, sometimes crying for no reason. Most of the time he lies in bed, in an embryonic position, at times looks around. Passive, does not want to do anything, reluctantly helps staff in labor processes.

Diagnosis. Simple schizophrenia, continuous course (F20.60). He received trifluoperazin therapy at a dose of 20 mg / day.

Upon admission to the clinic according to AIMS scales, unintentional movement disorders were not detected (0 - for all points), after examination after six weeks of therapy, the patient had facial dyskinesia: on the 1st scale, the severity was 2 points and manifested as unintentional movements of the forehead, eyebrows, the area around the eyes, cheeks; on the 2nd and 3rd scales - the severity was 1 point. For the correction of tardive dyskinesia, the patient was prescribed the anticholinergic drug cyclodol at a dose of 6 mg / day.

Laboratory indicators at admission to the clinic: GSH (reduced glutathione) - 105.141 mcg / ml; GSSG (oxidized glutathione) - 246.222 μg / ml; GSH / GSSG (ratio) - 0.427.

Thus, the proposed method is simple to implement and based on the determination of a number of laboratory parameters in blood serum, it is possible to predict the risk of developing tardive dyskinesia in patients with schizophrenia before treatment and to conduct individual therapeutic tactics for this category of patients using antipsychotics that do not cause side motor effects.

Literature

1. Jeste D.V., Wyatt R.J. Therapeutic strategies against tardive dyskinesia: two decades of experience. Arch Gen Psychiatry 1982; 39: 803-816.

2 Klawans H.L. Recognition and diagnosis of tardive dyskinesia // J. Clin. Psychiatry. - 1985. - Vol. 46, N4 (Sec. 2). - P.3-7.

3. Khot V., Egan M.F., Hyde T.M., Wyatt R.J. Neuroleptics and classic tardive dyskinesia / In: A.E. Lang, W.J. Weiner (Eds). Drug-induced movement disorders. - Mt. Kisco: Futura, 1992 .-- P.121-166.

4 Galecki P., Pietras T., Florkowki A. Pro- and antioxidant processes in schizophrenics with tardive dyskinesia. Psychiatr Pol. 2005 Nov-Dec; 39 (6): 1131-41.

5. Zhang XY, Tan YL, Zhou DF, Cao LY, Wu GY, Haile CN, Kosten TA, Kosten TR. Disrupted antioxidant enzyme activity and elevated lipid peroxidation products in schizophrenic patients with tardive dyskinesia // J Clin Psychiatry. 2007 May; 68 (5): 754-60.

6. Guy WA. Abnormal involuntary movement scale (AIMS). ECDEU Assessment Manual for Psychopharmacology. Washington, DC: US Department of Health Education and Welfare; 1976. p. 534-7.

7. American Psychiatric Association. Task force on tardive dyskinesia. Tardive dyskinesia: a task force report of the American Psychiatric Association. Washington DC: ARA; 1992.

8. Schooler NR, Kane JM (1982): Research diagnoses for tardive dyskinesia. Arch Gen Psychiatry 39: 486-487.

9. Hadithy A.F.Y. Al, Ivanova S.A., Pechlivanoglou P. et al. Tardive dyskinesia and DRD3, HTR2A and HTR2C gene polymorphisms in Russian psychiatric inpatients from Siberia // Progress in Neuro-Psychopharmacology & Biological Psychiatry. - 2009. - N.33. - P. 475-481.

10. Hissin P.J. A Fluorometric method for determination of oxidized and Reduced glutathione in tissues / P. Hissin, R. Hilf // Analyt. Biochem. - 1976 - Vol. 74. - P.214-226.

Claims (1)

A method for predicting the risk of developing tardive dyskinesia with neuroleptic therapy for schizophrenia patients, characterized in that the amount of reduced and oxidized glutathione and the ratio of reduced glutathione to oxidized in patients before treatment are used to determine the level of restored glutathione in the blood serum of the patients, while the restored glutathione is below 108 μg / ml the ratio of reduced glutathione to oxidized is below 0.49; a high risk of developing tardive dyskinesia in patients with background neuroleptic therapy.