RU2756614C1 - Method for supporting medical decisions on selection of antipsychotic therapy in patients with schizophrenia in order to prevent akathisia - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to psychiatry, and can be used to prevent the onset of akathisia in patients with schizophrenia on selection of an antipsychotic drug. The age of manifestation of schizophrenia, the duration of the disease, the overall score on the PANSS scale, the Tanner index and the waist circumference are determined. At the simultaneous value of the combination of indicators of: 1 – age of manifestation of schizophrenia of 19 years and earlier and the duration of the disease of 24 years and more; 2 – age of manifestation of schizophrenia of 19 and earlier and the duration of the disease of 4 years and less; 3 – age of manifestation of schizophrenia of 20 years and later, the Tanner index of 76 and greater; 4 – age of manifestation of schizophrenia of 20 years to 43 years, the Tanner index of 76 and greater, the overall score on the PANSS scale of 92 and the waist circumference from 77 cm to 102 cm, a high probability of development of akathisia is predicted and drugs with a low risk of onset of akathisia are prescribed.

EFFECT: ensures prediction of the probability of akathisia for supporting the medical decision on selection of antipsychotic therapy in patients with schizophrenia by evaluating a set of the most significant indicators.

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Description

The invention relates to medicine, in particular to psychiatry, and can be used to prevent the occurrence of akathisia in patients with schizophrenia when choosing an antipsychotic drug.

Akathisia is a drug-induced motor adverse event in patients with schizophrenia, which has objective and subjective components in its structure [1].

Antipsychotic therapy is the main treatment for schizophrenia. Therefore, the choice of basic therapy should be based not only on clinical efficacy, but also taking into account the development of side effects. The use of drugs from the group of antipsychotics plays an important role in maintaining and maintaining the quality of life and the level of social adaptation of patients with schizophrenia [2].

The prevalence of akathisia reaches 76% [1, 3]. And it differs against the background of taking each specific antipsychotic drug. Thus, when using haloperidol, akathisia occurs in 57% of cases [3]. Among atypical antipsychotics, risperidone (20%) and aripiprazole (20%) are associated with a high incidence of akathisia, while quetiapine and olanzapine are associated with a low incidence [3].

The main mechanism for the development of akathisia is a disturbance in the functioning of the dopaminergic systems of the brain, which is associated with the blockade of D2 / D3 dopamine receptors in the nigrostriatal and / or mesocortical and mesolimbic systems while taking antipsychotic drugs.

Clear predictors of the development of akathisia against the background of antipsychotic therapy have not been established [4]. Probably, its occurrence is closely related to the appointment of antipsychotic therapy, and the reasons for its development are heterogeneous and cannot be explained by the action of a single pharmacological agent. A limited number of works considers individual constitutional and morphological parameters as possible risk factors for the development of akathisia [5].

In recent years, intelligent systems or algorithms for supporting medical decision-making in medicine have begun to be used more widely at all stages of the treatment and diagnostic process.

In psychiatry, these developments are mainly aimed at selecting a rational pharmacological intervention for various mental disorders. For the choice of antipsychotic therapy in patients with schizophrenia in order to increase its effectiveness [6]. Predicting the development of concomitant somatic diseases [7].

The use of long-term neuroleptic therapy in the treatment of schizophrenia entails high economic costs, the occurrence of motor adverse events, namely akathisia, significantly worsens the quality of life of patients, causes the refusal of drug therapy, and determines the need to search for ways of early detection and prevention of this side effect.

An adequate prototype aimed at identifying the likelihood of akathisia in schizophrenic patients while receiving antipsychotic therapy was not found in the analyzed patent and scientific medical literature. This demonstrates the lack of methods for choosing an antipsychotic drug at the stage of selecting therapeutic tactics, which can be used to prevent akathisia.

The objective of the invention is to provide a method for predicting the likelihood of akathisia to support medical decision-making in the choice of antipsychotic therapy in schizophrenic patients.

The task is solved by determining the following clinical and dynamic characteristics: the age of manifestation of the schizophrenic process, the duration of the disease, the total score on the PANSS scale and parameters: Tanner index and waist circumference in schizophrenic patients. With the simultaneous fulfillment of the conditions in one of the 4 sets of signs, a high probability of akathisia is predicted. The first group of signs includes the age of manifestation of schizophrenia 19 years or less and the duration of the disease 24 years or more. The second set of signs: the age of manifestation of schizophrenia is 19 years or less and the duration of the disease is 4 years or less. The third set includes the age of onset of schizophrenia 20 years and more, the Tanner index equal to 76 and above. The fourth set of signs is represented by the age of onset of schizophrenia from 20 to 43 years, the Tanner index of 76 and above, the overall PANSS score of 92 and below, and the waist circumference from 77 to 102 centimeters.

New in the proposed method is the use of the selected sets of signs in support of medical decision-making in the choice of antipsychotic therapy in the treatment of schizophrenia, taking into account the likelihood of akathisia, at the stage of selecting therapeutic tactics (antipsychotics with a low likelihood of developing akathisia).

Distinctive features have shown in the claimed combination of new properties that are clearly not derived from the prior art in this area and are not obvious to a specialist. An identical set of features was not found in the patent and medical scientific literature.

The proposed method can be used in practical health care as a choice of individual therapeutic tactics for the prevention of the development of akathisia in patients with schizophrenia.

Based on the foregoing, the proposed invention should be considered as corresponding to the conditions of patentability: "Novelty", "Inventive level", "Industrial applicability".

The invention will be clear from the following description and the accompanying figure.

Clinical-dynamic and anthropometric examination of 214 patients with a verified diagnosis of schizophrenia was performed. Those who entered the clinic of the Research Institute of Mental Health of the Tomsk National Research Medical Center, OGBUZ "Tomsk Clinical Psychiatric Hospital", GKUZ of the Kemerovo Region, "Kemerovo Regional Clinical Psychiatric Hospital". Psychopathological symptoms were described according to the guidelines "Evaluation list of symptoms and a glossary for mental disorders" for ICD - 10. Before hospitalization, patients received maintenance antipsychotic therapy with drugs of various classes in recommended dosages for anti-relapse maintenance therapy.

Assessment of akathisia was performed two weeks after the patient was admitted to the hospital. This corresponds to the period of development of acute akathisia while receiving antipsychotic therapy.

Clinical assessment of akathisia was performed using the validated and standardized Barnes Akathisia Rating Scale (BARS) [8].

The leading clinical and psychopathological symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) [9].

Clinical and anthropometric examinations were carried out using the anthropometric method used for adult samples [10].

Somatic sex differentiation was calculated using the Tanner index [11] using the following formula:

Tanner index = 3BAD - 1BKD,

where

BAA - biacromial diameter

BKD - bicrystal diameter

The measurement of the waist circumference is made using a measuring tape.

Based on the Barnes akathisia rating scale (BARS) [8], two study groups were formed: 1 - patients with akathisia (N = 92; 50 men (54.3%), 42 women (45.7%); patients age - 41 [31; 52] year) and 2 - patients without akathisia (N = 122, men 62 (50.8%), women 60 (49.2%), patients' age - 39 [32; 49] years).

To determine the rules with a high probability of developing akathisia in schizophrenic patients, the Random Forests method (R version 3.6.3; package "RandomForest") was used. Next, the most informative parameters (according to the Gini Impurity index) in relation to the probability of akathisia development were identified and one decision tree was built (R version 3.6.3). This made it possible to facilitate the interpretation and visualization of the results obtained, while maintaining the classification accuracy. The target variable was the presence / absence of akathisia.

Based on the results of the analysis, a decision tree was built (Fig. 1).

Figure 1 shows:

1-17 - Nodes of separation are indicated

1 - Age of manifestation 20 years or more

2 - Tanner index less than 76

3 - The duration of the disease is less than 23 years

4 - Age of onset of the disease is less than 43 years

5 - Duration of the disease 5 years or more

6 - Total PANSS score of 93 or more points

7 - Waist circumference 102 and more centimeters

8 - Waist circumference less than 77 centimeters

9-12, 15 - Lack of akathisia

13-14, 16-17 - The presence of akathisia

A is the direction of the branch of the decision tree when the condition is met at the node

B is the direction of the branch of the decision tree if the condition in the node is not met

The age of disease manifestation ≥ 20 was chosen as the root of the decision tree (node 1), as the attribute with the highest value of the splitting criterion among all the others (“attribute usage” was 100%, which demonstrates the division of the sample by the target variable - the presence / absence of akathisia).

If the condition at node 1 is met, the tree branches to the left, where the next splitting attribute is the Tanner index <76 (node 2) (“attribute usage” was 74%), if this condition is not met, it branches to the right (node 3) disease duration <23 years ( "Attribute usage" was 26%), and forms its own branches of the tree. The following describes the way of forming all branches of the decision tree.

When the condition at node 2 is met, namely, with the Tanner index <76, the path leads to terminal node 9 - no akathisia (“attribute usage” was 10%, the probability of classification error was 9%).

If the condition - Tanner ≥76 is not met, node 4 is formed with further splitting according to the attribute age of disease manifestation <43 years (“attribute usage” was 64%).

Failure to meet the condition at node 4 (ie, age of disease manifestation ≥43 years), the decision tree branch leads to terminal node 14 - the presence of akathisia (“attribute usage” was 5%, the probability of classification error was 18%).

When the condition is met, namely at the manifestation age <43 years, the following branches of the tree are formed with the attribute - the total score on the PANSS scale (node 6) with its value ≥ 93 ("attribute usage" was 59%), the branch ends with terminal node 10 - the absence of akathisia (“attribute usage” was 44%, the probability of classification error was 31%). If the condition is not met, namely the total score on the PANSS scale <93, the branch moves to node 7 - waist circumference ≥102 (“attribute usage” was 15%). Splitting in this node under the condition where the waist circumference is ≥102 cm leads to terminal node 11 - the absence of akathisia (“attribute usage” was 5%, the probability of classification error was 27%). If the conditions are not met, with a waist circumference <102 cm, then the transition to node 8 (attribute - waist circumference <77 cm) ("attribute usage" was 10%), which ends with splitting into terminal nodes: 12 - no akathisia (" attribute usage "was 3%, the probability of classification error was 29%) for the condition that the waist circumference <77 cm. and 13 - the presence of akathisia (" attribute usage "was 7%, the probability of classification error was 14%) with a waist circumference of ≥77 cm.

If the condition at node 1 is not met (age of disease manifestation <20 years), the decision tree branches to the next attribute - disease duration <23 years (“attribute usage” was 26%), and if this condition is not met, the division ends with terminal node 17 - the presence of akathisia ( “Attribute usage” was 10%, the probability of classification error was 10%).

When executed, it splits into two branches with an attribute of disease duration ≥5 years (“attribute usage” was 16%), then terminal nodes are formed: 15 - no akathisia (“attribute usage” was 13%, the probability of classification error is 37%) with disease duration ≥ 5 years and 16 - the presence of akathisia (“attribute usage” was 3%, the probability of classification error was 14%) with a disease duration <5 years.

Evaluation of the effectiveness of the classification rules was performed using ROC analysis and determination of the area under the ROC curve. For the decision tree, it was 0.765, which indicates a qualitative classification.

The method proposed as an invention was tested on patients of the main sample. For this, the main sample was randomly divided into training (75% of the sample) and test (25% of the sample) models. For the training sample, the area under the ROC curve = 0.768, for the test sample - the area under the ROC curve = 0.751. This demonstrates a qualitative classification.

Thus, a set of signs with a high probability of occurrence of akathisia in schizophrenic patients were identified: 1 - the age of manifestation of schizophrenia is 19 years or less and the duration of the disease is 24 years or more; 2 - the age of manifestation of schizophrenia is 19 years or less and the duration of the disease is 4 years or less; 3 - the age of onset of schizophrenia is 20 years or more, the Tanner index is 76 and above; 4 - the age of onset of schizophrenia is from 20 to 43 years, the Tanner index is 76 and above, the overall PANSS score is 92 and below, the waist circumference is from 77 cm to 102 cm.

Clinical example 1. Patient P., 45 years old. Was undergoing treatment at the 2nd department of the Mental Health Research Institute. She fell ill at the age of 17, when multiple voices of a commenting nature appeared, delusional ideas of particular importance - she claimed that she was "the protector of all nature", and therefore made an attempt to penetrate a closed object. She was hospitalized for the first time in the Tomsk psychiatric hospital, diagnosed with paranoid schizophrenia, and prescribed antipsychotic therapy with risperidone at a dose of 4 mg / day. While taking this drug, there was a tremor in the hands that did not require correction. Subsequently, when taking the drug, she reported "stiffness" in the upper half of the body, a feeling of anxiety in the lower extremities and tension; for correction, trihexyphenidil was prescribed at a dose of 4 mg / day. After leaving school, she did not continue her studies. I tried to find a job as a seller in various stores in the city, and did not stay in any place for more than a few months. At the age of 24, the II group of disability was established. She was admitted to a psychiatric hospital annually. She lives with her parents, whose cold relationship, according to the words, "affects her emotional state." The condition worsened about a month ago, when verbal hallucinations, fragmentary ideas of particular importance, resumed. She began to wander aimlessly around the city. Accompanied by her mother, she was admitted to the clinic of the Research Institute of Mental Health. When determining the tactics of treatment aimed at choosing antipsychotic therapy with a low likelihood of developing akathisia, the following anamnestic information was taken into account: the age of onset of schizophrenia is 17 years and the duration of the disease is 28 years. As the antipsychotic drug of choice, the patient was recommended an antipsychotic with a low risk of developing akathisia olanzapine 10 mg / day. After two weeks of treatment, the patient was examined using the Barnes Akathisia Rating Scale (BARS), no akathisia was registered.

Summary. This clinical example demonstrates a set of signs with a high probability of occurrence of akathisia: if the age of manifestation of schizophrenia is 19 years or less and the duration of the disease is 24 years or more, then the probability of developing akathisia is high.

Clinical example 2. Patient K., 18 years old. He was treated in the 2nd clinical department of the Research Institute of Mental Health. This receipt is the second in a row. The debut of schizophrenia happened at the age of 16, when he stopped attending school, wandered around the city, became isolated, stopped communicating with friends, did not sleep. He was hospitalized at the insistence of his parents, during the hospitalization his mental status was characterized by Kandinsky-Clerambault syndrome, he heard the voices of “deceased ancestors”. The treatment used quetiapine up to 800 mg / day. She was discharged with a recommendation to take this drug, but at the outpatient stage, quetiapine was replaced by risperidone due to weight gain - 10 kg in 6 months. While taking risperidone, tremors of the hands and chin were noted, as well as a feeling of restlessness, due to which the patient slept poorly; trihexyphenidil was used at a dose of 4 mg / day to correct extrapyramidal adverse events. with a positive effect in the form of a decrease in tremor and a reduction in the feeling of restlessness. She lives with her grandmother and is on academic leave. Worsening about a week ago on the background of self-withdrawal of risperidone. He became withdrawn again, did not let grandmother into his room, covered the windows with newspapers. From the anamnesis it is known that the schizophrenic process developed at the age of 16, the duration of the disease at the time of the present admission to the hospital was 2 years. Due to the high risk of developing akathisia, according to the proposed method for predicting it, a low-risk antipsychotic drug for akathisia was chosen - paliperidone 6 mg / day. After two weeks of treatment, the patient was examined using the Barnes Akathisia Rating Scale (BARS), no akathisia was registered.

Summary. This clinical example demonstrates a set of signs with a high probability of occurrence of akathisia: if the age of manifestation of schizophrenia is the age of manifestation of schizophrenia is 19 years or less and the duration of the disease is 4 years or less, then the probability of development of akathisia is high.

Clinical example 3. Patient M., 29 years old. She is being treated in the 2nd clinical department of the Mental Health Research Institute. Early development was unremarkable. She graduated from the University of Architecture, after which she could not find a job in her specialty for a long time. She worked as an operator in a call center. She became acutely ill when she began to change in character - she became angry, distrustful, closely watched colleagues at work, expressed delusional ideas of a relationship. She also began to hear fragmentary voices "in her head" belonging to two men, urging her to "deal with a colleague." She was hospitalized in the direction of a local psychiatrist, whom she turned to in connection with insomnia. The treatment used intramuscular haloperidol up to 20 mg / day. On the background of treatment, a pronounced restlessness appeared, she constantly walked around the department. The condition was stopped with trihexyphenidil 4 mg / day. She was discharged in satisfactory condition, lived with her parents. After that, she was hospitalized annually due to the weakening of remission. This is the fifth in a row: voices resumed again, became restless, stopped sleeping. Before determining the treatment tactics, the patient underwent an anthropometric examination: Tanner index - 81.5. When determining the tactics of treatment aimed at choosing antipsychotic therapy with a low likelihood of developing akathisia, the following anamnestic information was taken into account: the age of onset of schizophrenia is 24 years. As the antipsychotic drug of choice, the patient was recommended an antipsychotic with a low risk of developing akathisia olanzapine 10 mg / day. After two weeks of treatment, the patient was examined using the Barnes Akathisia Rating Scale (BARS), no akathisia was registered.

Summary. This clinical example demonstrates a set of signs with a high probability of occurrence of akathisia: if the age of manifestation of schizophrenia is the age of manifestation of schizophrenia is 20 years or more, the Tanner index is 76 and higher, then the probability of developing akathisia is high.

Clinical example 4. Patient B., 32 years old. He was treated in the 2nd clinical department of the Research Institute of Mental Health. Until the 8th grade, he coped with the load, then changed in behavior, preferred to spend time alone, skipped school, left home and wandered aimlessly through the streets. After graduating from 9 classes, he entered the technical school. He fell ill at 22, when he refused to leave the house, for the first time voices of a threatening character appeared, which is why he covered his ears with his hands. For the first time he was hospitalized in a psychiatric hospital, diagnosed with paranoid schizophrenia. Received therapeutic doses of haloperidol. Was hospitalized annually in a psychiatric hospital, with symptoms of the "cliché" type. Visited a doctor on an outpatient basis. Since 2007, she has a mental health disability group. Previous extract in September 2015 After discharge, he took haloperidol 15 mg / day, while taking it, he was disturbed by pronounced tremor of the hands and a feeling of constriction in the cervical spine, which is why he was transferred to risperidone 4 mg / day 1 year ago. After a while, there was a feeling of anxiety in the lower extremities, also experienced a feeling of internal anxiety, tension, shifted from foot to foot, as prescribed by the doctor, the dose of risperidone was reduced to 2 mg / day, amantadine 300 mg / day was prescribed for correction, condition improved somewhat. Lives with her parents. The condition changed about a week ago. Verbal hallucinations were actualized. Decreased mood, disturbed sleep, stopped communicating with relatives. At the insistence of his relatives, he again turned to the clinic of the Research Institute of Mental Health. Before determining the treatment tactics, the patient underwent an anthropometric examination, the waist circumference was 83 cm, the Tanner index was 81. From the anamnesis it is known that the schizophrenic process developed at 22 years, the duration of the disease at the time of the present admission to the hospital was 10 years. PANSS psychometric examination revealed a total score of 90. The antipsychotic drug of choice for this patient was the antipsychotic with a low risk of developing akathisia olanzapine 10 mg / day. After two weeks of treatment, the patient was examined using the Barnes Akathisia Rating Scale (BARS), no akathisia was registered.

Summary. This clinical example demonstrates a set of signs with a high likelihood of akathisia: if the age of onset of schizophrenia is from 20 years to 43 years, the Tanner index is 76 and above, the overall PANSS score is 92 and below, the waist circumference is from 77 cm to 102 cm. , then the likelihood of developing akathisia is high.

List of used literature

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Claims (1)

A method of supporting medical decision-making in the choice of antipsychotic therapy in schizophrenic patients in order to prevent akathisia, characterized by the fact that they determine the age of onset of schizophrenia, the duration of the disease, the total PANSS score, the Tanner index and the waist circumference and, at the same time, a set of signs: 1 - the age of manifestation of schizophrenia is 19 years or less and the duration of the disease is 24 years or more; 2 - the age of manifestation of schizophrenia is 19 years or less and the duration of the disease is 4 years or less; 3 - the age of onset of schizophrenia is 20 years or more, the Tanner index is 76 and above; 4 - the age of onset of schizophrenia is from 20 to 43 years, the Tanner index is 76 and above, the overall PANSS score is 92 and below, the waist circumference from 77 cm to 102 cm predicts a high probability of developing akathisia and prescribes drugs with a low risk of occurrence akathisia.

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