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QT interval prolongation in schizophrenia: A cross-sectional study from a tertiary care center in Raipur
For correspondence: Dr Aditya Somani, Department of Psychiatry, All India Institute of Medical Sciences Raipur, Tatibandh, Raipur 492 099, Chhattisgarh, India e-mail: dr.adityasomani@aiimsraipur.edu.in
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Received: ,
Accepted: ,
Abstract
Background & objectives
Antipsychotic drugs can cause QT interval prolongation (QTIP), which can lead to life-threatening cardiac manifestations. The objective of this study was to find out the prevalence of QTIP in stable patients of schizophrenia attending the outpatient department/clinic.
Methods
A total of 88 consenting individuals with schizophrenia aged ≥18 yr of either sex (male or female), who were stable on treatment and adherent to the prescribed medications, were included. Patients with any other psychiatric disorder, mental retardation, substance dependence other than caffeine/nicotine, or if they had taken any other drug with moderate to high risk of causing QTIP, were excluded. A 12-lead ECG was recorded. Corrected QT interval was calculated using Fridericia’s and Bazett’s formulae.
Results
QTIP was seen in 3 (3.4%) study participants according to Fridericia’s formula and in 6 (6.8%) study participants according to Bazett’s formula. The recorded demographic, anthropometric, and clinical/treatment variables did not differ among participants with and without QTIP.
Interpretation & conclusions
Prevalence of antipsychotic drug-induced QTIP in patients with schizophrenia seems to be low, but it poses a risk to life. Regular screening for additional risk factors and periodic assessment of cardiac rhythm via ECG could help prevent potentially fatal cardiac manifestations.
Keywords
Antipsychotic drugs
ECG
patient safety
QT interval prolongation
Schizophrenia
Torsades de Pointes
Schizophrenia is a severe and debilitating mental illness leading to considerable loss of disability-adjusted life years (10% in India, 1900-2017)1. Patients with schizophrenia need treatment with antipsychotic drugs, which could cause QT interval prolongation (QTIP) in the electrocardiogram (ECG) of patients. The QT interval in ECG is measured from the beginning of the QRS complex to the end of the T-wave. The measured QT interval is corrected for heart rate and is then known as the corrected QT interval (QTc)2. QTIP is present if QTc is >460 msec in females and QTc >450 msec in males2. QTIP is associated with a potentially life-threatening arrhythmia, known as Torsades de Pointes (TdP), which may manifest as syncope or cardiac arrest2,3. The prevalence of QTIP in patients getting psychotropic drugs varies from 3.4-11.6 per cent across studies.4-10
The present study was conducted keeping these issues in consideration. Our objective was to find out the prevalence of QTIP in stable patients of schizophrenia attending the outpatient department/clinic.
Materials & Methods
This cross-sectional study was conducted from October to December 2023 in the Psychiatry outpatient department of All India Institute of Medical Sciences, Raipur, Chhattisgarh, India, after approval from its Institute Ethics Committee. The participants provided written informed consent before inclusion. Individuals with schizophrenia who were diagnosed as per ICD-10 DCR11, aged ≥18 yr, of either sex (male or female), stable on treatment and at least 90 per cent adherent to the prescribed treatment, were included. An individual was considered stable on therapy if they had been on adequate treatment for at least the last six months and did not require any increase in the dose of antipsychotic medication for the previous three months12. The participants were excluded if they had any other psychiatric disorder, organic mental disorder, or mental retardation, had substance dependence other than caffeine or nicotine or if they were getting any drugs during the last 15 days that were included in the first two risk categories of the list of drugs that prolong QT interval (CredibleMeds list)13.
Based on the prevalence of QTIP as 5.7 per cent in a previous study4, five per cent probability of type 1 error and an absolute error limit of five per cent, the sample size was calculated to be around 83. Sociodemographic details and clinical profile (diagnosis, duration of illness, and current treatment) were recorded. The Brief Adherence Rating Scale (BARS) was used to determine treatment adherence14.
Schiller (Florida, US) AT-2 ECG machine was used to record an ECG. The QT interval was measured using the tangent method2. Corrected QT interval (QTc) was calculated primarily using Fridericia’s formula and additionally with Bazett’s formula. QTIP was defined as QTc > 460 msec in females and QTc > 450 msec in males2.
The continuous and nominal variables were described using mean and standard deviation (SD) and frequencies and percentages, respectively, and compared using Student’s t-test and Fisher’s exact test, respectively. A two-sided P<0.05 was considered statistically significant.
Results
A total of 88 study participants were included in the study, of which 54 (61.4%) were males. The mean age of the study participants was 34.74 yr (SD±13.2; Table). The average duration of the disorder in the study participants was 61.8 months (SD 70.58). A few had hypertension (9.1%), cardiovascular disease (5%), thyroid disorders (5%), and diabetes mellitus (9.1%). Of the study participants, 60 (68.2%) were not using any substance. Around 15 per cent were using tobacco products.
| Variables | Mean (±SD)/n (%) N=88 |
|---|---|
| Age (yr) | 34.74 (13.2) |
| Sex | |
| Male | 54 (61.4) |
| Female | 34 (38.6) |
| Residence | |
| Rural | 54 (61.4) |
| Urban | 34 (38.6) |
| Education (yr) | 9.84 (3.71) |
| Occupation | |
| Unemployed | 67 (76.1) |
| Employed | 21 (23.9) |
| Monthly family income (₹) | 15,675 (20,491.51) |
| Type of Family | |
| Nuclear | 55 (62.5) |
| Joint | 33 (37.5) |
| Marital status | |
| Married | 44 (50) |
| Never married | 41 (46.6) |
| Widow/ widower | 2 (2.3) |
| Divorced | 1 (1.1) |
| Religion | |
| Hinduism | 86 (97.7) |
| Islam | 2 (2.3) |
Age, education and monthly income variables are expressed as mean (SD). SD, standard deviation
Olanzapine was the most frequently prescribed antipsychotic (46.6%), followed by risperidone (36.4%), aripiprazole (9.1%), clozapine (4.5%), and quetiapine (3.4%). Additionally, usage of trihexyphenidyl and benzodiazepines was noted in 29 (33%) and 24 (27.3%) study participants, respectively. The treatment regimen of 15 study participants included the use of an additional antipsychotic, of which four study participants were getting long-acting antipsychotics like haloperidol decanoate and paliperidone palmitate. Seven study participants were also getting an antidepressant. All the participants scored ≥90 per cent on the BARS.
In this study, 3 (3.4%) of the 88 participants had QTIP (QTc calculated according to Fridericia’s formula). All of them were getting olanzapine. The recorded demographic, anthropometric, clinical, and treatment variables (use of trihexyphenidyl/benzodiazepines) did not differ among study participants with and without QTIP.
When QTc was calculated using Bazett’s formula, it was seen that 6 (6.8%) of the study participants had QTIP. Among these, three study participants were receiving olanzapine, two study participants were receiving aripiprazole, and one was receiving risperidone.
Discussion
In this study, 3 (3.4%) had QTIP (QTc calculated according to Fridericia’s formula). This finding is similar to the study conducted by Polcwiartek et al8, in which the prevalence of QTIP was 3.4 per cent. Ali et al4, reported a slightly higher prevalence of QTIP (5.7%).Using Bazett’s formula, the prevalence of QTIP was 6.8 per cent among the participants, nearly similar to the studies conducted by Ozeki et al7 (5.6%) and Yang et al15 (4.5%). The difference in prevalence figures arrived at using two methods of estimation of QTc is notable. However, Fridericia’s method is considered superior to the popular Bazett’s formula2. In this study, the demographic and clinical variables of the patients with and without QTIP did not differ significantly, which is in sync with the study conducted by Rettenbacher et al9. Other studies have found female sex4,10,15,16, hypertension4,10, older age, high potassium levels, and increased number of antipsychotics in the treatment regimen as risk factors for QTIP10.
The use of second-generation antipsychotic drugs, with most getting only one drug, and the limited number of participants with medical comorbidities could explain the difference in the prevalence of QTIP noted in this study. Use of first-generation antipsychotics, polypharmacy, and the presence of medical comorbidities are known risk factors for QTIP2,5,10,16. Additionally, there may be a difference in the genetic composition of the population being studied. The studies cited were conducted in Italy, China, Denmark, Norway, Taiwan, Austria, and Japan. A study comprising 2,553 patients with schizophrenia from 15 Asian countries found the prevalence of QTIP to be 1.1 per cent17.
There are a few limitations in our investigation. The sample size was not large enough to identify risk factors. Being a cross-sectional study, the presence of QTIP before initiation of antipsychotic drugs could not be ruled out. Lastly, the patients were not tested for imbalance of electrolytes (potassium, calcium, and magnesium).
Overall, this study showed that the prevalence of QTIP in stable individuals of schizophrenia in this study was different from studies conducted elsewhere. However, the development of QTIP leading to TdP could result in serious cardiac events. Hence, medical practitioners should be aware of the possible adverse effects and observe necessary precautions. Timely interventions like screening for comorbidities, avoiding polypharmacy, switching to medications with low risk, and referring to a specialist in case of the development of QTIP are of utmost importance. Multicentric studies with a large sample could help identify risk factors for QTIP and improve patient safety.
Financial support & sponsorship
The study received financial support by the Indian Council of Medical Research (ICMR), New Delhi under the Short Term Studentship program, for the year 2023, awarded to the the first author (MM).
Conflicts of Interest
None.
Use of Artificial Intelligence (AI)-Assisted Technology for manuscript preparation
The authors confirm that there was no use of AI-assisted technology for assisting in the writing of the manuscript and no images were manipulated using AI.
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