| BackgroundAmisulpride is a kind of benzamide antipsychotic drug,which is widely used in clinic because of its high efficacy and good tolerance.In addition to the treatment of schizophrenia,amisulpride is also used to treat depression and other diseases.QTc interval reflects the time from the beginning of depolarization to the end of repolarization of ventricular muscle.Prolonged QTc interval often reflects the abnormality of cardiac conduction function,which can lead to arrhythmia,torsades de pointes(Tdp)and even sudden death.In recent years,there have been many clinical studies and case reports on the QTc interval prolongation,Tdp and sudden death caused by amisulpride administration.In consideration of the heart safety of patients taking amisulpride in our hospital,the weekly electrocardiogram(ECG)tests are required for patients taking amisulpride since 2016.In order to investigate whether amsulpide has a significant effect on QTc interval,medical records of patients who took amisulpride during hospitalization from January 2016 to September 2018 were collected in this study,in order to determining whether it is necessary to regularly monitor ECG while taking amisulpride.Objective(1)To study the effect of amisulpride administration on QTc interval of ECG in patients,and determine whether it is necessary to monitor ECG frequently while taking amisulpride.(2)To investigate the effects of different risk factors on QTc interval during amisulpride administration,including duration of medication,dosage,gender,age,and number of combination drugs.(3)To explore the contribution rate of different risk factors on QTc interval,in order to provide individualized guidance for patients to carry ECG detection.MethodsA total of 444 patients were screened,who were hospitalized in our hospital between January 2016 and September 2018 and received amisulpride.Then their ECG data,general demographic data and blood biochemical test data were extracted.The information was collected and proofread by two psychiatric graduate students.The ECG monitoring frequency of the selected patients was greater than or equal to once every 2 weeks(once every 2 weeks was chosen because there were fewer patients with ECG monitoring frequency once a week).The diagnostic criteria for prolonged QTc interval was male QTc interval >450ms,female QTc interval >470 ms;clinically significant prolongation of QTc interval was observed when QTc interval extended more than 30 ms from baseline.Rank-sum test and chi-square test were used to compare the difference of QTc interval composition ratio in ECG among each group.Risk function graph was used for the relationship between the incidence of QTc interval prolongation and time.Repeated measure ANOVA was used to analyze the QTc interval differences between groups before and after medication.The interaction among risk factors was tested by analysis of variance of mixed design.Pearson correlation analysis was used for the correlation analysis of continuity variables.The correlation test,risk contribution rate,risk score and fitting function of each risk factor were performed by principal component analysis and factor analysis.SPSS22.0 was used as statistical software,and P < 0.05 was considered statistically significant.Results(1)Of the 444 patients,a total of 160 patients were diagnosed with prolonged QTc interval after taking amisulpride and prolonged QTc interval more than 30 ms from baseline.Among them,32(7.21%)cases were diagnosed with prolonged QTc interval,and 2(0.45%)cases were diagnosed with QTc interval greater than500 ms.There were 152(34.23%)patients with QTc interval longer than 30 ms from baseline,29(6.53%)patients with QTc interval longer than 60 ms from baseline,and 2(0.45%)patients with QTc interval longer than 100 ms from baseline.The cumulative number of patients diagnosed with prolonged QTc interval after taking amisulpride and with QTc interval extended by more than 30 ms from baseline increased rapidly at the beginning of the treatment(about 4 weeks).(2)The overall mean baseline QTc interval was 409.82±23.39 ms.At the 4th,6th and 8th week after taking the drug,the QTc interval of different durations was3.16 ms,5.11 ms and 5.73 ms longer than the baseline QTc interval,respectively,and the difference was statistically significant(P<0.05).(3)Risk factors that have different effects on QTc interval include: duration of medication,dose of medication,age and gender;The influence of risk factors on QTc interval was statistically significant(P<0.05).(4)Male patients aged 18-45 are taking medication[400-600)mg/d,the interval of 6 weeks and 8 weeks after taking medicine was 7.01 ms、13.36 ms longer than that of baseline QTc(P <0.05);Male patients aged 18-45 are on medication[1000-1200)mg/d,6 weeks after taking medicine and 8 weeks after taking medicine were prolonged by 17.57 ms、14.84 ms compared with baseline QTc(P <0.05);In female patients aged 18-45[600-800)mg/d,the QTc interval of the 2nd week,4th week,6th week and 8th week was 15.72 ms、14.76ms、14.17ms、11.01 ms longer than that of baseline QTc(P <0.05).(5)There was a positive weakly correlated linear relationship between age and QTc interval(P<0.05);among the patients aged 18-45 years,QTc interval at week 2,4,6 and 8 was 3.10 ms,3.97 ms,5.56 ms and 6.68 ms longer than baseline,respectively,and the difference was statistically significant(P<0.05);QTc interval of patients under18 years old fluctuated greatly after taking medication,but there was no statistically significant difference from baseline QTc interval.The average QTc interval of patients over 45 years old before and after medication was longer than that of patients under 45 years old,and there was no statistically significant difference in QTc interval from baseline after medication.(Only 3 patients were over 65 years old,so they were included in the study group over 45 years old.)(6)There were significant differences between male in the 6th week and 8th week after taking the drug,5.67 ms、6.93 ms,compared with the baseline QTc period(P<0.05);female in the 6th week and 8th week after taking the drug were 4.65 ms compared with the baseline QTc period(P<0.05);when taking the drug dose of more than 400 mg/d,the significant difference between male and female was 30.3% and46.5% respectively(P<0.05).5.42%(13 cases)and 5.88%(12 cases)of male and female patients extended more than 60 ms from baseline after taking medication,respectively.The frequency of male and female patients extending more than 30 ms from baseline was 31.67%(76 cases)and 37.25%(76 cases),respectively.The changes in QTC interval occurred earlier in women than in men,and the difference was statistically significant(P<0.05).(7)When the dosage was [600-800)mg/d、[800-1000)mg/d and [1000-1200),the obvious prolongation rates were 47.5%,31.5% and 46.5% respectively;the 75%QTC-free interval was significantly prolonged by 4 weeks.There was no statistically significant difference between [600-800)mg/d and [1000-1200)mg/d,but there was statistically significant difference between them and other drug doses(P<0.05).(8)There was no significant difference in the amount of amisulpride combined with different drugs(mainly antipsychotics).The QTc interval after taking amisulpride alone or in combination with another drug was longer than the baseline,and the difference was statistically significant.When amisulpride was combined with the two drugs,the QTc interval was longer than the baseline,and the difference was not statistically significant.When amisulpride was combined with the three drugs,the QTc interval was shorter than the baseline,and the difference was not statistically significant.(9)The results of principal component analysis and factor analysis showed that medication time(F1),dosage(F2),gender(F3),age(F4),combined dosage(F5)were correlated with each other(P<0.05);the contribution rates were 27.414%,12.902%,12.058%,11.843%,11.381%,respectively,and the fitting function was F=(27.414%F1+12.902%F2+12.058%F3+11.843%F4+11.381%F5)/75.599%Conclusions(1)There is a risk of prolonged QTc interval with taking amisulpride.Most of the patients taking amisulpride had QTc interval changes in the early stage of medication.No matter whether the patients have a high risk of prolonged QTc interval at the beginning of medication,ECG should be monitored no less than once a week.In the later stage of medication,regular ECG examination at different frequencies can be carried out according to the different risk levels of the patients.(2)The related risk factors include duration of medication,dosage,age and gender(female).The QTc interval was prolonged with the the increase duration of amisulpride administration.The QTc interval was more likely to be prolonged when the dose was more than 400 mg per day.The older the patients were,the longer the QTc interval was.The QTc interval of patients aged 18 to 45 years old were prone to prolonged with the increase of medication duration of amisulpride.And the QTc interval fluctuates greatly in patients under 18 years old.Women were more likely to experience QTC interval changes than men after amisulpride treatment. |
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