Method and system for curative effect evaluation and drug withdrawal decision support of depression drugs

Abstract

The invention belongs to the field of biological medicine, and particularly relates to a method and a system for curative effect evaluation and drug withdrawal decision support of depression drugs. It has been found that the platelet 5-HT concentration can be used as an objective index of the curative effect of the antidepressant drug and drug withdrawal indication, a drug withdrawal decision-making system based on the platelet 5-HT concentration is constructed, and the platelet 5-HT concentration is combined with the blood concentration of the drug, the HAMD score of a depression patient and basic information of the depression patient. Compared with a conventional decision making system, the specific decision making formula designed by the invention can be used for realizing a more accurate drug withdrawal decision. In addition, a drug withdrawal decision-making system and a drug effect evaluation method based on the platelet 5-HT concentration are combined, and a complete depression drug effect evaluation and drug withdrawal decision-making system suitable for clinical application is developed.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine, and in particular relates to a method and system for evaluating the efficacy of depression drugs and supporting drug discontinuation decisions. Background Art

[0002] Depression is a common psychiatric disorder characterized by persistent low mood, loss of interest, and low energy, which severely impacts patients' quality of life and social functioning. Currently, the treatment of depression primarily relies on medications, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). However, the effectiveness of current medications is primarily assessed based on patient experience and neuropsychological assessments, such as the Hamilton Depression Rating Scale (HAMD) and the Montgomery Depression Rating Scale, which are subject to certain subjectivity. Some patients even conceal their condition, complicating the evaluation of treatment efficacy for depression.

[0003] Furthermore, there is a lack of precise decision-making tools for the timing of discontinuation of antidepressants (such as SSRIs). Premature discontinuation can easily lead to relapse, while long-term use can cause adverse effects (such as metabolic syndrome and sexual dysfunction). The treatment cycle recommended by existing guidelines is a universal concept, but due to significant individual variability, it cannot yet achieve the goal of personalized treatment.

[0004] Antidepressants primarily improve depressive symptoms by increasing 5-HT concentrations in the synaptic cleft. Current methods for measuring central 5-hydroxytryptamine (5-HT) concentrations primarily include cerebrospinal fluid and PET-CT, which are invasive, expensive, and pose radiation risks. The peripheral platelet 5-HT system is reciprocally regulated by the central nervous system. Elevated central 5-HT levels by drugs may inhibit 5-HT synthesis or release in peripheral platelets through a negative feedback mechanism, leading to decreased peripheral concentrations. As an easy-to-use, minimally invasive, and objective biomarker, 5-HT is expected to provide a more reliable basis for evaluating the efficacy of depression medications and making decisions about discontinuation. Summary of the Invention

[0005] The platelet 5-HT transporter shares homology with the neuronal 5-HT transporter (protein sequence similarity >92%), but its use as an objective indicator of antidepressant drug efficacy and discontinuation indications has not previously been considered. The present inventors have discovered that changes in platelet 5-HT concentration are not correlated with overall levels in the brain's central nervous system, and therefore platelet 5-HT levels cannot be used to reflect the symptoms of depressive patients. However, changes in platelet 5-HT concentration decrease under the effects of drugs such as SSRIs, and plasma 5-HT concentrations are unrelated to antidepressant medications. To develop new applications for platelet 5-HT concentration in antidepressant drug efficacy and discontinuation indications, the present inventors have developed a discontinuation decision-making system based on platelet 5-HT concentration. By combining platelet 5-HT concentration with the drug's blood concentration, the HAMD score of the depressed patient, and basic information about the depressed patient, and utilizing a specific decision-making formula designed by the present invention, more accurate discontinuation decisions can be made than with conventional decision-making systems. Furthermore, the present invention also combines the drug discontinuation decision system with a drug efficacy evaluation method based on platelet 5-HT concentration to develop a complete depression drug efficacy evaluation and drug discontinuation decision system suitable for clinical application.

[0006] Specifically, in a first aspect, the present invention provides a depression drug discontinuation decision-making system, the system comprising:

[0007] Data acquisition module: regularly detecting the platelet 5-HT concentration and the blood concentration of the drug in the peripheral blood of patients with depression receiving drug treatment, evaluating the HAMD score of the patients with depression, and collecting basic information of the patients with depression;

[0008] Data processing and analysis module: receives data from the data acquisition module, processes and analyzes the data using the discontinuation decision formula to assess the risk of discontinuation; and

[0009] Decision output module: Based on the results obtained by the data processing and analysis module, it outputs the risk of drug discontinuation, thereby providing drug discontinuation decision support for patients with depression receiving drug treatment;

[0010] The drug discontinuation decision formula is:

[0011]

[0012] Among them, CRI is a comprehensive risk index, which indicates the risk of drug discontinuation: when CRI ≥ 60, it indicates a low risk of drug discontinuation, and when CRI < 60, it indicates a high risk of drug discontinuation;

[0013]

[0014] λ=0.2

[0015]

[0016] Among them, C i The platelet 5-HT concentration is measured regularly;

[0017]

[0018] Among them, T 达标 is the number of consecutive HAMD scores that meet the target during regular assessment, where the target is HAMD ≤ 7 points; γ = 2; θ = 5; σ HAMD is the standard deviation of the HAMD score;

[0019]

[0020] Among them, w i w age =0.4, w gender =0.3 or w recur =0.3;Ri∈{0,1};

[0021]

[0022] Among them, CV drug is the coefficient of variation of blood drug concentration; K=50.

[0023] As used herein, methods for detecting platelet 5-HT concentration are known in the art and can be routinely selected by those skilled in the art as needed. As an example, a method for detecting platelet 5-HT concentration can include collecting a peripheral blood sample from a patient receiving depression medication, isolating and enriching platelets from the peripheral blood sample, and detecting the 5-HT concentration in the isolated platelets using, for example, high-performance liquid chromatography (HPLC). Those skilled in the art are aware of other assay methods other than HPLC that can be used to detect 5-HT.

[0024] As used herein, a depression medication is a selective serotonin reuptake inhibitor (SSRI).

[0025] In a specific embodiment, the depression medication is paroxetine.

[0026] In a second aspect, the present invention provides a depression drug efficacy evaluation and drug discontinuation decision-making system, comprising:

[0027] Data acquisition module: regularly detecting the platelet 5-HT concentration and the blood concentration of the drug in the peripheral blood of patients with depression receiving drug treatment, evaluating the HAMD score of the patients with depression, and collecting basic information of the patients with depression;

[0028] Efficacy evaluation module: Determines whether medication for depression is effective based on set conditions. If ineffective, continues treatment or changes medication. If effective, assesses the risk of discontinuation. The set conditions are: 4-6 weeks after treatment, the 5-HT concentration drops below the threshold or drops to 40-50% of the baseline value, the HAMD scale score drops by ≥25%, and the blood drug concentration returns to the normal range, and the medication treatment is considered effective.

[0029] Data processing and analysis module: receives data from the data acquisition module, processes and analyzes the data using pre-set algorithms and models to assess the risk of drug discontinuation; and

[0030] Decision output module: Based on the results obtained by the data processing and analysis module, it provides support for the decision to stop medication for patients with depression who are receiving medication;

[0031] The drug discontinuation decision formula is:

[0032]

[0033] Among them, CRI is a comprehensive risk index, which indicates the risk of drug discontinuation: when CRI ≥ 60, it indicates a low risk of drug discontinuation, and when CRI < 60, it indicates a high risk of drug discontinuation;

[0034]

[0035] λ=0.2

[0036]

[0037] Among them, C i The platelet 5-HT concentration is measured regularly;

[0038]

[0039] Among them, T 达标 is the number of consecutive HAMD scores that meet the target during regular assessment, where the target is HAMD ≤ 7 points; γ = 2; θ = 5; σ HAMD is the standard deviation of the HAMD score;

[0040]

[0041] Among them, w i w age =0.4, w gender =0.3 or w recur =0.3;Ri∈{0,1};

[0042]

[0043] Among them, CVdrug is the coefficient of variation of blood drug concentration; K=50.

[0044] In some embodiments, the pre-set threshold is 148-165 ng / 10 9 (Indicates every 10 9 Each platelet contains 148-165 nanograms).

[0045] As used herein, a drop below a predetermined threshold value refers to a drop below a predetermined threshold value (148-165 ng / 10 9 ) range (including the end value) or below the threshold value.

[0046] As used herein, baseline value or baseline concentration refers to the platelet 5-HT concentration of a depressed patient at the time of initiation of treatment.

[0047] As used herein, the normal range of drug blood concentration can be determined by those skilled in the art according to routine practice based on the actual drug used. For example, the normal blood concentration range of paroxetine is 20-65 ng / ml.

[0048] As used herein, regular monitoring or regular evaluation refers to monitoring or evaluation every week, month, every two months, every three months, every four months, every five months, every six months, or every year after the start of treatment.

[0049] In a preferred embodiment, regular monitoring or regular assessment refers to monitoring or assessment every three months after the start of treatment.

[0050] In a more preferred embodiment, regular monitoring or regular assessment includes monitoring or assessment at 4-6 weeks after the start of treatment and every three months after the start of treatment.

[0051] In some embodiments, the drug treatment is treatment with a selective serotonin reuptake inhibitor (SSRI).

[0052] In some embodiments, the drug is paroxetine.

[0053] As used herein, HAMD refers to the Hamilton Depression Rating Scale (HAMD). Using HAMD to score patients with depression is well known in the art.

[0054] In some embodiments, the basic information of the depression patient includes the age, gender and course of the depression patient. In some embodiments, the basic information of the depression patient may also include other information of the patient.

[0055] As used herein, the course of illness refers to the patient's history of depression, including, for example, the first episode, relapse, and remission period after relapse.

[0056] As used herein, T 达标 is the number of consecutive HAMD scores that meet the target in regular assessments, where the target is HAMD ≤ 7 points. For example, if the sequence of HAMD scores in regular assessments is 17 → 10 → 7 → 7, and the last two scores meet the target (7 → 7), then T 达标 =2, if the sequence of HAMD scores in regular assessments is 7→8→8→6, and the score is only achieved for the last time (6 points), then T 达标 =1.

[0057] As used herein, σ HAMD is the standard deviation of the HAMD score, indicating the actual fluctuation degree of the HAMD score.

[0058] As used herein, Ri∈{0,1} is the existence indicator (existence=1, absence=0) of each static risk factor (i.e., age, gender, and disease course-related static risk factors). For example, if the age range is 18-60 years old, then there is no age-related static risk factor, R age =0, otherwise R age =1; if the gender is male, there is no gender-related static risk factor, R gender =0, otherwise R gender =1; if the patient has a first episode of depression, there are no static risk factors related to the course of the disease, R recur =0, otherwise R recur =1.

[0059] Advantageous Effects of the Invention

[0060] The present invention has developed a drug discontinuation decision-making system based on platelet 5-HT concentration. By combining platelet 5-HT concentration with the blood concentration of the drug, the HAMD score of the depression patient, and the basic information of the depression patient, and using the specific decision-making formula designed by the present invention, it can achieve more accurate drug discontinuation decisions than conventional decision-making systems.

[0061] The innovation of the decision formula of the present invention is:

[0062] 1. Combination of dynamic and static data

[0063] Multi-dimensional heterogeneous data fusion mechanism: Dynamic data (temporal changes in platelet 5-HT concentration, fluctuations in HAMD scores, and coefficient of variation of blood drug concentration) are coupled with static data (age, gender, and disease course) through nonlinear formulas (rather than simple weighting). For example: ① Static risk factors are directly calculated through logical operations (R_age∨R_gender∨R_recur); ② The temporal attenuation factor of dynamic data (δ=0.95^t) and the weight distribution of static data (10%) form a cross-dimensional interaction.

[0064] Technical comparison: Traditional methods mostly use a single dynamic indicator (such as only HAMD score) or static stratification (such as age grouping), while this patent achieves a coordinated analysis of cross-time scales (dynamic) and inherent characteristics (static) through mathematical modeling, reflecting the biological effects of drugs through dynamic data (declining trend of platelet 5-HT concentration), and using static data (such as disease course) to correct long-term recurrence risk.

[0065] Unique Algorithm Design: Dynamic Data Drives, Static Data Modifies: In the CRI formula, dynamic platelet analysis accounts for 70% of the weight, while static risk only accounts for 10%. However, static data directly influences the decision threshold (a CRI < 60 forces a high-risk determination) through Boolean logic thresholds (the presence of any static risk factor triggers a penalty term). For example, if a patient's platelet indicators are good (a high dynamic score), but if there is a static risk (such as age > 60), the system will directly lower the CRI value through the ∨ operation in the formula. This design is unique in medical decision-making systems.

[0066] 2. Innovation of multi-dimensional dynamic evaluation model

[0067] Time series analysis of platelet 5-HT concentrations uses a unique "maximum month-on-month decline rate" metric (max(ΔCi / Ci)), combined with a time decay factor (δ=0.95^t) to enhance the weight of recent data. This dynamic modeling approach is innovative in biomarker analysis.

[0068] The coefficient of variation of blood drug concentration was transformed nonlinearly (CV^3), and the fluctuation characteristics were amplified by cubic method, which enhanced the sensitivity of the model to concentration fluctuations.

[0069] 3. Nonlinear parameter coupling mechanism

[0070] The HAMD score is calculated based on the number of consecutive times the target is reached using an exponential gain design with γ = 2 ((n / γ)^θ). When the number of consecutive times the target is reached accumulates, a nonlinear acceleration effect will occur. This parameter coupling method is original in the assessment of mental illness.

[0071] The static risk factor realizes the joint judgment of multiple factors through logical operation (R_age∨R_gender∨R_recur) rather than simple weighted summation.

[0072] 4. Time Series Data Fusion Mechanism

[0073] During the efficacy evaluation stage, the 4-6 week detection window and the 3-month regular detection are required to be connected in time, and a complete drug response trajectory is constructed through multi-time scale data integration (acute phase response + long-term monitoring). BRIEF DESCRIPTION OF THE DRAWINGS

[0074] Figure 1 Shown is a comparison of 5-HT in patients with depression before and after medication.

[0075] Figure 2 A comparison of two discontinuation decisions is shown.

[0076] Figure 3 A flowchart showing an example of a method for evaluating the efficacy of depression medication and a drug discontinuation decision-making system using peripheral platelet serotonin (5-HT) concentration detection. DETAILED DESCRIPTION

[0077] The research of this invention is based on the research project of healthy aging molecular atlas and its quantitative evaluation system (project number: 2022YFC3600600).

[0078] The present invention firstly detected the platelet 5-HT levels of patients from the healthy control group, the unmedicated depression group and the medication treatment group (treated for more than 6 weeks). Figure 1 As shown, it shows that platelet 5-HT is highly sensitive to SSRIs citalopram. The data were non-normally distributed. Using Kruskal-Wallis H test, the healthy control group (558.02±199.35ng / 10 9 ), unmedicated depression group (646.40±259.03ng / 10 9 ) and the drug treatment group (57.35±36.46ng / 10 9 There were significant differences among the three groups (H = 68.514, p = 0.000). Patients treated with citalopram for more than 6 weeks had significantly lower platelet 5-HT levels than those in the untreated healthy control group and the newly diagnosed depression group (p < 0.05). There was no statistically significant difference in platelet 5-HT levels between the healthy control group and the newly diagnosed depression group (Z = -1.326, p > 0.05).

[0079] Based on the above results, the present invention develops an antidepressant efficacy evaluation and discontinuation decision support method and system by combining the blood concentration of antidepressants and the platelet 5-HT concentration on the basis of the current HAMD subjective evaluation.

[0080] Methods for evaluating the efficacy of antidepressant drugs

[0081] The present invention's method for evaluating the efficacy of depression medications based on peripheral platelet 5-HT concentration testing involves assessing a patient's HAMD and platelet 5-HT concentration before medication administration, reassessing HAMD four to six weeks after the patient takes the antidepressant, and simultaneously measuring the corresponding antidepressant's blood concentration and platelet 5-HT concentration to assess efficacy. The following are the specific steps for testing and evaluation.

[0082] Sample Collection: Peripheral blood samples are collected from patients with depression, typically using venous blood collection, with a volume of 5 ml. Strict aseptic operation procedures should be followed during the collection process to avoid sample contamination.

[0083] Platelet separation and enrichment: The collected peripheral blood sample is centrifuged to obtain a platelet-rich plasma layer. Gradient centrifugation can be used, initially centrifuging at a low speed to sediment the red blood cells and white blood cells. The upper plasma layer is then collected and centrifuged again at a higher speed to further concentrate the platelets. The first centrifugation is performed at a speed of 500 r / min for 30 minutes, and the second centrifugation is performed at a speed of 4000 r / min for 20 minutes. The upper platelet-poor plasma layer is then discarded, and platelet wash solution at 8°C is added to the centrifuge tube. The contents are gently shaken to mix, and 300 μl of the mixture is taken for calculation. The remaining portion is centrifuged at 8000 r / min for 20 minutes. 600 μl of deionized water is added to cause hypotonic rupture of the platelets, and the platelets are stored at -80°C until HPLC analysis.

[0084] 5-HT concentration detection: High-Performance Liquid Chromatography (HPLC) detection method is used to detect the 5-HT concentration in the separated platelets. The sample from the previous step is then injected into the HPLC system, separated by the chromatographic column, and the height of the analyte peak is calculated and compared with the standard peak. The 5-HT standard is analyzed before and after the experimental sample for drift correction. The value of the amount of 5-HT in each sample is standardized and expressed as 5-HT ng / 10 9 Report.

[0085] Efficacy evaluation: The 5-HT concentration detected was compared with the pre-set threshold (148-165ng / 10 9) to assess the efficacy of drug treatment. Furthermore, drug efficacy is confirmed when the HAMD score decreases by ≥25%, the drug blood concentration reaches the normal range, and the platelet 5-HT concentration decreases to 40-50% of the baseline value. This means that the patient is responding to medications such as paroxetine.

[0086] Decision support methods for discontinuing antidepressants

[0087] The present invention provides a method for supporting decision-making for discontinuation of depression medication based on peripheral platelet 5-HT concentration detection. The method includes regularly (e.g., every three months) testing platelet 5-HT concentration after a patient takes an antidepressant, assessing HAMD, and simultaneously testing the corresponding antidepressant's blood concentration. The method then processes and analyzes the data using a discontinuation decision formula based on the patient's basic information (age, gender, and course of disease). The method outputs a discontinuation risk, thereby providing clinicians with discontinuation decision recommendations. When a patient meets the discontinuation criteria, the physician is prompted to consider discontinuation and is provided with information such as a follow-up plan and precautions after discontinuation.

[0088] Drug discontinuation decision formula:

[0089] The platelet 5-HT dynamic model, static risk factors, HAMD symptom relief, and blood drug concentration stability were integrated to establish a nonlinear multi-stage decision-making formula and calculate the Composite Risk Index (CRI):

[0090]

[0091] Threshold interpretation: CRI ≥ 60 → low risk of discontinuation; CRI < 60 → high risk of discontinuation Core indicator interpretation:

[0092] 1. Platelet time series dynamic analysis (weight 70%)

[0093]

[0094] -Δ norm : Normalized interval stability score

[0095]

[0096] -λ=0.2 (time decay factor, strengthening the weight of recent data)

[0097] - Maximum month-on-month decline rate

[0098]

[0099] 2. Static risk factor (weight 10%)

[0100]

[0101] -Risk weight: w age =0.4,w gender =0.3,w recur =0.3

[0102] 3. HAMD symptom relief score (weight 10%)

[0103] Scoring Rules:

[0104] -Parameter definition:

[0105] -T 达标 :Number of consecutive times reaching the target (HAMD≤7 points)

[0106] -γ=2(Nonlinear gain of the number of times the target is reached)

[0107] -θ=5 (fluctuation tolerance threshold)

[0108] 4. Blood drug concentration stability model (weight 10%)

[0109]

[0110] -Parameter definition:

[0111] -k=50 (high sensitivity to suprathreshold fluctuations)

[0112] -CV drug : Coefficient of variation of blood drug concentration

[0113] Antidepressant discontinuation decision system

[0114] The present invention provides an antidepressant drug discontinuation decision-making system based on platelet 5-HT concentration detection, which comprises:

[0115] Platelet 5-HT concentration detection module: Regularly detect the platelet 5-HT concentration in peripheral blood of patients with depression receiving drug treatment;

[0116] Blood drug concentration detection module: regularly detects the blood drug concentration of drugs in the peripheral blood of patients with depression who are receiving drug treatment;

[0117] Patient information collection module: collects basic information of the depression patient;

[0118] HAMD assessment module: regularly assess the HAMD score of the depression patient;

[0119] Data processing and analysis module: Receives data output by the 5-HT detection module, combines the patient's basic information (age, gender, disease course), clinical symptom assessment data (HAMD scale score) and blood concentration of antidepressants, and uses pre-set algorithms and models to process and analyze the data to assess the risk of drug discontinuation.

[0120] Decision Support Module: Based on the results from the Data Processing and Analysis Module, the module outputs the risk of drug discontinuation, providing clinicians with a drug efficacy assessment report and discontinuation decision-making recommendations. When a patient meets the discontinuation criteria (i.e., the risk of discontinuation is low), the system automatically prompts the physician to consider discontinuing the medication and provides information such as a follow-up plan and precautions after discontinuation.

[0121] Antidepressant efficacy evaluation and discontinuation decision system

[0122] The present invention provides a depression drug efficacy evaluation and drug discontinuation decision-making system based on platelet 5-HT concentration detection, which includes:

[0123] Data acquisition module: regularly detecting the platelet 5-HT concentration and the blood concentration of the drug in the peripheral blood of patients with depression receiving drug treatment, evaluating the HAMD score of the patients with depression, and collecting basic information of the patients with depression;

[0124] Efficacy evaluation module: Determine whether depression medication is effective based on set conditions. If not, continue treatment or switch medications. If effective, assess the risk of discontinuation.

[0125] Data processing and analysis module: receives data from the data acquisition module, processes and analyzes the data using pre-set algorithms and models to assess the risk of drug discontinuation; and

[0126] Decision output module: Based on the results obtained by the data processing and analysis module, the drug discontinuation risk is output, thereby providing drug discontinuation decision support for patients with depression receiving drug treatment.

[0127] Figure 3 This example illustrates an application of the drug efficacy evaluation and discontinuation decision system of the present invention. It includes testing platelet 5-HT concentration, HAMD score, and blood drug concentration in the fourth week of treatment to assess efficacy. If the treatment efficacy criteria are not met, treatment is continued or the medication is switched. If the treatment efficacy criteria are met, the test data, combined with the patient's basic information, is input into the data processing and analysis module of the discontinuation decision system for calculation, thereby outputting the discontinuation risk. If the discontinuation risk is low, a discontinuation decision can be made; if the discontinuation risk is high, a decision can be made not to discontinue the treatment, and the patient can continue treatment or switch medications.

[0128] The present invention is further described below with reference to specific examples, which, however, are not intended to limit the present invention in any way. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in the art.

[0129] Example 1: Application of a method for evaluating the efficacy of depression medication and supporting discontinuation decisions based on peripheral platelet serotonin (5-HT) concentration detection

[0130] Study subjects: Patient X, a 45-year-old male, had a first-episode of depressive disorder and was treated with paroxetine.

[0131] Research Methodology:

[0132] (1) Assessment of blood concentrations of HAMD and antidepressants

[0133] Assessment of HAMD: The HAMD-24-item rating scale should be used and should be jointly examined by two trained assessors. The assessment should be conducted before taking the medication and at the 4th week, 3rd month, 6th month, 9th month, and 12th month after taking the medication.

[0134] To measure antidepressant blood concentrations, draw 3-5 ml of venous blood on an empty stomach in the morning before taking medication (to ensure trough concentrations are measured) using heparinized blood collection tubes. After blood collection, centrifuge the blood within 30 minutes (3000 rpm for 10 minutes) to separate the plasma into cryovials. Drug concentrations are measured using high-performance liquid chromatography-tandem mass spectrometry (LC-MS / MS).

[0135] (2) Sample collection

[0136] In the morning, while fasting, a 5ml peripheral blood sample was collected from a vein in the elbow of a patient with depression using a disposable sterile needle and a vacuum blood collection tube. An appropriate amount of anticoagulant (such as EDTA-K2) was pre-added to the tube to prevent blood clotting. After collection, the tube was gently inverted several times to thoroughly mix the blood and anticoagulant. The sample was then stored in a refrigerator at 4°C until further processing.

[0137] (3) Platelet separation and enrichment

[0138] The collected peripheral blood sample is centrifuged to obtain a platelet-rich plasma layer. Gradient centrifugation can be used. First, centrifuge at a lower speed to precipitate the red blood cells and white blood cells, then collect the upper plasma layer and centrifuge at a higher speed to further concentrate the platelets. The first centrifugation speed is 500r / min and the centrifugation time is 30min; the second centrifugation speed is 4000r / min and the centrifugation time is 20min. Then, discard the upper platelet-poor plasma and add 8°C platelet washing solution to the centrifuge tube. Gently shake the contents to mix, take 300μl of the mixture for calculation, and centrifuge the remaining portion at 8000r / min for 20min. Add 600μl of deionized water to cause hypotonic rupture of the platelets and store at -80°C until HPLC analysis.

[0139] (IV) 5-HT concentration detection

[0140] The 5-HT concentration in the isolated platelets was determined using an HPLC assay. The sample from the previous step was then injected into the HPLC system, separated by the chromatographic column, and the height of the analyte peak was calculated and compared with the standard peak. The 5-HT standard was analyzed before and after the experimental sample for drift correction. The value of the amount of 5-HT in each sample was normalized and expressed as 5-HT ng / 10 9 Report.

[0141] (V) Efficacy evaluation

[0142] The normal reference range of platelet 5-HT concentration is set at 148-165 ng / 10 9 The normal blood concentration of paroxetine is 20-65 ng / ml. Patient X's platelet 5-HT concentration was 605 ng / 10 at baseline. 9 , HAMD score 30 points. After four weeks of treatment with paroxetine, the blood concentration was 30ng / ml and the platelet 5-HT concentration was 301.4ng / 10 9 The HAMD assessment scale is 20 points. Based on the efficacy evaluation, if the HAMD scale score decreases by ≥25% at 4 weeks, the blood concentration of the drug reaches the normal range, and the platelet 5-HT concentration decreases to 40-50% of the baseline value, the drug is confirmed to be effective and the patient is judged to be effective with paroxetine.

[0143] (VI) Drug discontinuation risk assessment

[0144] Patient X continued to take paroxetine 30mg / day. The platelet 5-HT concentration was 160.7ng / 10 9 , HAMD score 17 points, blood drug concentration was 40ng / ml, and the platelet 5-HT concentration was 155.4ng / 10 9, HAMD score 10 points, platelet 5-HT concentration was 149.4ng / 10 9 , HAMD score 7 points, blood drug concentration was 40ng / ml, and the platelet 5-HT concentration was 148.5ng / 10 at the 12th month. 9 , a HAMD score of 7, and a blood paroxetine concentration of 42 ng / ml. These patient data were substituted into the discontinuation decision formula for data processing and analysis. This prediction was based on the patient's 5-HT concentration trend, paroxetine blood concentration, and improvement in the HAMD scale score. The patient's CRI score was calculated to be 89.08, indicating a low risk for discontinuation. This met the indications for discontinuation and could be discontinued under a physician's guidance.

[0145] Comparative Example:

[0146] The discontinuation decision-making system of the present invention was compared with the decision-making system using the scale to evaluate the patient's discontinuation decision. Specifically, a cohort of depressed patients who attempted to discontinue medication was included. Each patient was subjected to two decision-making systems (the scale scoring system was recommended or not recommended for discontinuation; the decision-making system of the present invention was the CRI score). The outcome variable was whether the discontinuation was successful (defined as no relapse within 6 months after complete discontinuation of medication). After controlling for covariates, the ROC curve was drawn. The comparison of the two decision-making systems is shown in Figure 2. Figure 2 The results show that the drug discontinuation decision-making system of the present invention has higher sensitivity and specificity.

[0147] It should be noted that the preferred embodiments of the present invention are given in the specification and drawings of the present invention. However, the present invention can be implemented in many different forms and is not limited to the embodiments described in this specification. These embodiments are not intended to be additional limitations on the content of the present invention. The purpose of providing these embodiments is to make the understanding of the disclosure of the present invention more thorough and comprehensive. In addition, the above-mentioned technical features can be combined with each other to form various embodiments not listed above, which are all considered to be within the scope of the description of the present invention. Furthermore, it is obvious to those skilled in the art that improvements or changes can be made based on the above description, and all such improvements and changes should fall within the scope of protection of the claims attached to the present invention.

Claims

1. A depression drug discontinuation decision system, characterized by: The system comprises: Data acquisition module: regularly detecting the platelet 5-HT concentration and the blood concentration of the drug in the peripheral blood of patients with depression receiving drug treatment, evaluating the HAMD score of the patients with depression, and collecting basic information of the patients with depression; Data processing and analysis module: receives data from the data acquisition module, processes and analyzes the data using the discontinuation decision formula to assess the risk of discontinuation; and Decision output module: Based on the results obtained by the data processing and analysis module, it outputs the risk of drug discontinuation, thereby providing drug discontinuation decision support for patients with depression receiving drug treatment; The drug discontinuation decision formula is: Among them, CRI is a comprehensive risk index, which indicates the risk of drug discontinuation: when CRI ≥ 60, it indicates a low risk of drug discontinuation, and when CRI < 60, it indicates a high risk of drug discontinuation.

2. The system according to claim 1, wherein: In the discontinuation decision formula: Among them C i The platelet 5-HT concentration is measured regularly.

3. The system according to claim 1, wherein: In the discontinuation decision formula: in, T 达标 The number of consecutive HAMD scores that meet the target in regular assessments, where the target means HAMD ≤ 7 points; γ = 2; θ = 5; σ HAMD is the standard deviation of the HAMD score.

4. The system according to claim 1, wherein: In the discontinuation decision formula: in, w i w age =0.4, w gender =0.3 or w recur =0.3; Ri∈{0,1}.

5. The system according to claim 1, wherein: In the discontinuation decision formula: in, CV drug is the coefficient of variation of blood drug concentration; K＝50。 6. The system according to claim 1, wherein: The depression drug is a selective serotonin reuptake inhibitor.

7. The system according to claim 6, characterized in that The depression drug is paroxetine.

8. A depression drug efficacy evaluation and discontinuation decision-making system, characterized by: include: Data acquisition module: regularly detecting the platelet 5-HT concentration and the blood concentration of the drug in the peripheral blood of patients with depression receiving drug treatment, evaluating the HAMD score of the patients with depression, and collecting basic information of the patients with depression; Efficacy evaluation module: Determines whether medication for depression is effective based on set conditions. If ineffective, continues treatment or changes medication. If effective, assesses the risk of discontinuation. The set conditions are: 4-6 weeks after treatment, the 5-HT concentration drops below the threshold or drops to 40-50% of the baseline value, the HAMD scale score drops by ≥25%, and the blood drug concentration returns to the normal range, and the medication treatment is considered effective. Data processing and analysis module: Receives data from the data acquisition module and processes and analyzes the data using pre-set algorithms and models to assess the risk of drug discontinuation; and Decision output module: Based on the results obtained by the data processing and analysis module, it provides support for the decision to stop medication for patients with depression who are receiving medication; The drug discontinuation decision formula is: Among them, CRI is a comprehensive risk index, which indicates the risk of drug discontinuation: when CRI ≥ 60, it indicates a low risk of drug discontinuation, and when CRI < 60, it indicates a high risk of drug discontinuation.

9. The system according to claim 8, characterized in that In the discontinuation decision formula: λ=0.2 Among them, C i The platelet 5-HT concentration is measured regularly; Among them, T 达标 is the number of consecutive HAMD scores that meet the target during regular assessment, where the target is HAMD ≤ 7 points; γ = 2; θ = 5; σ HAMD is the standard deviation of the HAMD score; Among them, w i w age =0.4, w gender =0.3 or w recur =0.3;Ri∈{0,1}; Among them, CV drug is the coefficient of variation of blood drug concentration; K=50.

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