Antipsychotic drugs remain a central component of treatment for schizophrenia spectrum disorders, bipolar affective disorder, acute psychosis, severe agitation, and selected behavioural syndromes. Their therapeutic action is balanced against a range of metabolic, neurological, endocrine, and cardiovascular adverse effects. Among cardiovascular effects, prolongation of the corrected QT interval (QTc) has special clinical relevance because it reflects delayed ventricular repolarization and can create an electrophysiological substrate for torsades de pointes, syncope, ventricular fibrillation, and sudden cardiac death [1,2]. Although these outcomes are uncommon, their severity has made QTc evaluation an important aspect of psychopharmacological safety.

The QT interval varies with heart rate; therefore, clinical interpretation usually relies on a corrected value. QTc values above accepted sex-specific thresholds, very large increments from baseline, and values reaching or exceeding 500 ms are considered warning signals in drug safety practice [3,4]. Antipsychotic-related QTc prolongation occurs mainly through interference with cardiac repolarizing potassium currents, especially the rapid component of the delayed rectifier current. The magnitude of QTc change differs between individual drugs and is influenced by dose, route of administration, metabolic inhibition, serum concentration, and patient susceptibility [4-7].

Earlier investigations and reviews have shown that both first-generation and second-generation antipsychotics can produce measurable QTc changes, but the effect is not uniform across agents [4-7]. Haloperidol, thioridazine, ziprasidone, and some antipsychotic combinations have received particular attention, whereas several atypical agents have shown smaller average effects under usual dosing conditions [4-6]. Population-level studies have also linked antipsychotic exposure with sudden cardiac death, especially at higher doses and in patients with additional cardiovascular vulnerability [8,9]. These findings support careful patient selection rather than avoidance of clinically necessary antipsychotic treatment.

Risk assessment is especially important because QTc prolongation is usually multifactorial. Female sex, older age, baseline cardiac disease, electrolyte abnormalities, bradycardia, hepatic or renal dysfunction, high antipsychotic dose, polypharmacy, and use of other QT-prolonging psychotropic or non-psychotropic drugs all increase vulnerability [10-13]. Contemporary guidance recommends ECG monitoring when patients receive moderate- or high-risk antipsychotics, when risk factors are present, or when clinically significant QTc prolongation develops during treatment [11,12].

Despite extensive international literature, local data from psychiatric settings remain useful because prescribing patterns, comorbidity profiles, ECG access, and monitoring practices differ between institutions. The present study was conducted to evaluate QTc interval changes among patients receiving antipsychotic drugs in a psychiatry department. The objectives were to assess baseline and follow-up QTc values, determine the frequency of QTc prolongation, and identify demographic, clinical, and treatment-related factors associated with QTc prolongation among patients receiving antipsychotic therapy.

MATERIALS AND METHODS

Study design and setting

This hospital-based observational analytical study was conducted in the Department of Psychiatry, All Saints University School of Medicine, Roseau, Dominica. The study was carried out over a six-month period from September 2025 to February 2026. The study evaluated QTc interval changes among adult patients receiving antipsychotic medication as part of routine psychiatric care. The design involved assessment of baseline clinical profile, antipsychotic exposure, electrocardiographic findings, and follow-up QTc measurements.

Study population

A total of 120 patients receiving antipsychotic drugs were included. Adult patients aged 18 years and above who were prescribed antipsychotic medication for schizophrenia spectrum disorder, bipolar affective disorder, acute psychosis, or other psychiatric indications were eligible. Patients were included when baseline and follow-up ECG records were available and clinical data were sufficiently complete for analysis. Patients with congenital long QT syndrome, pacemaker rhythm, bundle branch block preventing reliable QT assessment, acute myocardial infarction, severe decompensated cardiac illness, or incomplete ECG documentation were excluded to reduce measurement bias and clinical confounding [8,10].

Data collection

Data were collected using a structured case record form. Demographic variables included age and sex. Clinical variables included psychiatric diagnosis, hypertension, diabetes mellitus, history of cardiac disease, and family history of cardiac illness. Drug-related variables included the antipsychotic prescribed, monotherapy or polytherapy status, duration of treatment, and concomitant psychotropic medication. Available serum electrolyte findings were reviewed, and abnormalities relevant to QTc risk were documented. Antipsychotic drug use was categorized according to the primary agent received, and polytherapy was defined as concurrent use of more than one antipsychotic drug.

ECG assessment and operational definitions

Standard 12-lead electrocardiograms were assessed at baseline and follow-up. QT interval was measured from the beginning of the QRS complex to the end of the T wave, and QTc was calculated using a standard correction formula. QTc prolongation was defined using sex-specific clinical thresholds, while QTc ≥500 ms and QTc increase greater than 60 ms from baseline were considered clinically important safety outcomes [3,11,12]. ECGs with unclear T-wave termination or artefacts affecting QT measurement were not used for final analysis.

Statistical analysis

Data were entered into a spreadsheet and analysed using standard statistical methods. Continuous variables were expressed as mean ± standard deviation. Categorical variables were presented as frequency and percentage. Baseline and follow-up QTc values were compared using paired statistical testing. Associations between QTc prolongation and selected risk factors were assessed using chi-square test or Fisher exact test according to cell distribution. A p-value <0.05 was considered statistically significant.

Ethical considerations

The study was conducted in accordance with institutional ethical standards and the principles of the Declaration of Helsinki. Ethical approval was obtained from the Institutional Ethics Committee of All Saints University School of Medicine, Roseau, Dominica, before data collection. Written informed consent was obtained from study participants. Confidentiality was maintained by anonymizing patient identifiers during data entry and analysis.

RESULTS

A total of 120 patients receiving antipsychotic drugs were included in the analysis. The mean age of the study population was 39.6 ± 12.8 years, with most patients belonging to the 31-45 years age group. Males constituted 56.7% of the study population. Schizophrenia spectrum disorders were the most common indication for antipsychotic therapy, followed by bipolar affective disorder and acute psychosis. Hypertension and diabetes mellitus were present in 14.2% and 10.8% of patients, respectively. A family history of cardiac illness was reported in 8.3% of participants (Table 1).

Table 1. Baseline demographic and clinical characteristics of the study population

Risperidone was the most commonly prescribed antipsychotic drug, followed by olanzapine and quetiapine. Most patients were receiving monotherapy, while 18.3% were receiving more than one antipsychotic drug. Concomitant use of antidepressants or mood stabilizers was noted in 34.2% of patients. Electrolyte abnormality was documented in 10.0% of the study population (Table 2).

Table 2. Pattern of antipsychotic drug use among the study participants

The mean baseline corrected QT interval was 408.6 ± 22.4 ms. After antipsychotic exposure, the mean QTc interval increased to 424.8 ± 28.7 ms. The mean QTc increase was 16.2 ± 18.9 ms, and this change was statistically significant. QTc prolongation was observed in 18 patients, representing 15.0% of the study population. A QTc increase of more than 60 ms was observed in 5 patients, while QTc ≥500 ms was recorded in 2 patients (Table 3).

Table 3. QTc interval changes before and after antipsychotic therapy

QTc prolongation was more frequently observed among patients receiving haloperidol, antipsychotic polytherapy, and those with electrolyte abnormalities. Female sex, older age, and concomitant psychotropic medication also showed higher proportions of QTc prolongation, although the strongest associations were observed with haloperidol use, polytherapy, and electrolyte imbalance. Age >60 years, haloperidol use, antipsychotic polytherapy, concomitant psychotropic medication, electrolyte abnormality, and history of cardiac disease were significantly associated with QTc prolongation (Table 4).

Table 4. Factors associated with QTc prolongation among patients receiving antipsychotic drugs

Overall, antipsychotic therapy was associated with a statistically significant increase in QTc interval. However, clinically marked QTc prolongation was limited to a small proportion of patients. Patients receiving haloperidol, multiple antipsychotic drugs, concomitant psychotropic medication, and those with electrolyte abnormalities demonstrated a higher frequency of QTc prolongation, indicating the need for baseline and follow-up electrocardiographic monitoring in these risk groups.

DISCUSSION

The present study evaluated QTc interval changes in 120 patients receiving antipsychotic drugs and demonstrated a statistically significant increase in mean QTc from baseline to follow-up. The observed mean increase of 16.2 ms suggests that antipsychotic therapy produced measurable but generally modest ventricular repolarization delay in this cohort. This finding is consistent with earlier pharmacological and clinical studies reporting variable QTc effects across antipsychotic agents rather than a uniform class effect [4-7]. Although the mean change was significant, QTc ≥500 ms occurred in only 1.7% of patients, indicating that marked prolongation was uncommon.

QTc prolongation was observed in 15.0% of patients at follow-up. This proportion is clinically meaningful because the psychiatric population often carries overlapping risk factors, including comorbid medical illness, concomitant psychotropic therapy, and variable access to periodic ECG monitoring. Large psychiatric inpatient studies have reported that ECG abnormalities and QTc prolongation occur in a notable minority of patients, and risk rises when drug exposure coincides with patient-related vulnerability [13,14]. In the current study, the presence of cardiac disease and older age showed significant associations with QTc prolongation, supporting the importance of baseline risk stratification before prescribing higher-risk antipsychotic regimens.

Haloperidol use was significantly associated with QTc prolongation. This observation agrees with previous reviews and updated psychotropic safety literature describing haloperidol as an antipsychotic requiring careful monitoring, particularly in patients with medical illness, higher doses, parenteral exposure, or additional risk factors [2,10,11]. In contrast, risperidone and olanzapine were more frequently prescribed in the overall study population but were not highlighted as the strongest risk signals in the present analysis. This pattern supports the view that both drug-specific electrophysiological properties and host factors shape the final QTc response [5-7].

Antipsychotic polytherapy was another significant factor associated with QTc prolongation. Polytherapy increases pharmacodynamic burden, creates potential pharmacokinetic interactions, and often reflects greater psychiatric severity. Concomitant psychotropic medication was also significantly associated with QTc prolongation, which is relevant because antidepressants, mood stabilizers, sedatives, and other agents can influence cardiac conduction directly or indirectly [10,12]. These findings support a medication review approach in which clinicians evaluate total QT burden rather than considering each drug in isolation.

Electrolyte abnormality showed the strongest association with QTc prolongation in this study. Hypokalemia, hypomagnesemia, and hypocalcemia are established contributors to delayed repolarization and torsades vulnerability [8,9,13]. The association observed here reinforces the practical need to correct reversible biochemical abnormalities before continuing or escalating QT-prolonging antipsychotic treatment. Female sex showed a higher proportion of QTc prolongation, although the association was not statistically significant. Previous reports have consistently identified female sex as a risk factor, but the absence of significance in this study could reflect sample size and the distribution of other risk factors [10,13].

The clinical implication of this study is that ECG monitoring should be targeted and systematic. Baseline ECG is particularly valuable in patients above 60 years, those with cardiac disease, patients receiving haloperidol or antipsychotic combinations, and individuals exposed to additional psychotropic drugs or electrolyte imbalance. Follow-up ECG after initiation, dose escalation, or addition of interacting medication can identify early repolarization changes and allow timely intervention. Dose optimization, correction of electrolytes, reduction of avoidable polytherapy, and selection of lower-risk alternatives are practical strategies for preventing severe QTc prolongation while preserving psychiatric stability [11,12].

LIMITATIONS

This study was limited by its single-centre design, modest sample size, and short follow-up duration. Serum drug levels and genetic susceptibility markers were not assessed. QTc measurement was based on available ECG records, and long-term arrhythmic outcomes were not evaluated. These factors restrict broader generalization of the findings.

CONCLUSION

In this study, antipsychotic therapy was associated with a statistically significant increase in QTc interval among adult psychiatric patients. Most QTc changes were modest, while QTc ≥500 ms and QTc increase greater than 60 ms were observed in a small proportion. Haloperidol use, antipsychotic polytherapy, concomitant psychotropic medication, electrolyte abnormality, older age, and cardiac disease were important risk factors. These findings support baseline ECG evaluation, correction of reversible biochemical abnormalities, careful medication review, and follow-up ECG monitoring in high-risk patients. Safer prescribing requires balancing psychiatric benefit with individualized cardiac risk assessment.

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