QT-prolonging antipsychotic combinations and associated risk in hospitalized patients with mental disorders in Sana’a, Yemen

Abstract

Prolongation of the QT interval is associated with serious and potentially life-threatening

cardiac complications, requiring careful clinical attention. Psychiatric inpatients frequently receive multiple antipsychotic medications, some of which are known to affect cardiac repolarization. This study aimed to describe the patterns of QT-prolonging antipsychotic drug combinations and their associated drug–drug interaction (DDI) risk among hospitalized male participants in Sana’a, Yemen. A retrospective cross-sectional study was conducted using medical records of inpatients admitted to two psychiatric hospitals between November 2023 and June 2024. A total of 191 male participants aged 17–65 years who received antipsychotic polypharmacy for at least one week were included. Electrocardiogram (ECG) monitoring at admission was available for 47 participants. Prescribed medications were screened for QT-prolonging potential and interaction severity using the Arizona Center for Education and Research on Therapeutics (AZCERT) database. Overall, 395 QT-prolonging antipsychotic prescriptions were identified. Among participants receiving antipsychotic combinations, 36% were prescribed at least one strong-to-moderate QT-prolonging combination. Of the 47 participants who underwent ECG monitoring, 39.3% received drugs classified by AZCERT as having a known risk of torsades de pointes (TdP). Borderline QTc intervals were observed in 10.6% of participants, while 6.4% exhibited prolonged QTc intervals. These findings highlight the presence of QTc abnormalities within a pre-selected subgroup of psychiatric inpatients already receiving QT-prolonging antipsychotic polypharmacy. While no cases of TdP were observed, the results underscore the importance of enhanced clinical vigilance, routine ECG monitoring, and careful selection of antipsychotic combinations. Future studies including comparator groups are needed to quantify the incremental risk of QTc prolongation and TdP.

Supplementary Information

The online version contains supplementary material available at 10.1038/s41598-026-55180-x.

Introduction

Drug–drug interactions (DDIs) are defined as clinically relevant changes in the effect of a drug caused by the concomitant administration of another medication. Potential drug–drug interactions (pDDIs) refer to combinations that may result in adverse outcomes, regardless of whether clinical harm is immediately observed^1–3. QT interval prolongation represents a major concern in pharmacovigilance and drug safety, as it is associated with increased morbidity, prolonged hospitalization, and higher mortality rates. Psychiatric participants are particularly vulnerable to drug-induced^4–6. QT prolongation because many antipsychotic and antidepressant medications affect cardiac repolarization. Several antipsychotics—especially first-generation agents such as phenothiazines—are well known for their association with QT prolongation, torsades de pointes (TdP), and sudden cardiac death^7–10. Although individual antipsychotics have been extensively studied, limited data are available regarding the additive or synergistic effects of antipsychotic polypharmacy on QTc prolongation^11,12. Given the widespread use of antipsychotic combinations in clinical practice and the scarcity of data from low-resource settings^6,13, this study was designed to evaluate the prevalence and clinical profile of QT-prolonging antipsychotic combinations, along with their potential risk as assessed using established risk classification tools among hospitalized psychiatric participants in Sana’a, Yemen.

Material and method

Study design and setting

A retrospective cross‑sectional study was conducted in the psychiatry departments of two psychiatric hospitals in Sana’a city. Medical records of participants admitted between November 2023 and June 2024 were reviewed, as illustrated in Scheme 1. Ethical approval was obtained from the Research Committee of Al Nasser University (Code: NU RECM2309). Because the study was retrospective and relied on anonymized medical records, the requirement for informed consent was waived by the ethics committee. All procedures were performed in accordance with institutional guidelines and international research regulations.

Scheme 1.

Flowchart of the study design.

Study population

Patients aged ≥ 18 years with a confirmed psychiatric diagnosis who were receiving two or more antipsychotic medications during hospitalization for at least seven consecutive days were eligible. Patients with incomplete or missing medical records, monotherapy, or insufficient treatment duration were excluded. Of 324 patients initially screened, 133 were excluded (incomplete records, monotherapy, or insufficient treatment duration), leaving 191 male participants for analysis. Only male participants were included because the participating psychiatric hospitals admit male patients exclusively, reflecting local institutional admission policies.

This study was restricted to psychiatric inpatients already receiving QT-prolonging antipsychotic polypharmacy. Therefore, the analysis focuses on the characteristics and risks of QTc prolongation within this high-risk subgroup, rather than estimating the overall prevalence of QT-prolonging antipsychotic use among all psychiatric inpatients.

Data collection collected data included demographic characteristics

Psychiatric diagnoses, medication use, ECG findings, electrolyte levels, and heart rate measurements. Heart rate was obtained from the same electrocardiograms (ECGs) used for QT interval analysis. Baseline ECGs were recorded within 48 h of admission under resting conditions, with participants in the supine position. Follow-up ECGs were performed after reaching steady-state drug concentrations. Heart rate values were automatically generated by the ECG machine and verified by a cardiologist to ensure accuracy.

Drug classification and interaction assessment

Psychiatric disorders in this study included schizophrenia spectrum disorders, bipolar disorder, and depressive disorders. QTc prolongation was defined as QTc > 450 ms, while borderline QTc prolongation was defined as QTc values between 430 and 450 ms. QT-prolonging antipsychotics were classified according to the AZCERT (CredibleMeds) database as having known or possible risk of torsades de pointes (TdP). QTc intervals were analyzed as continuous variables (median, IQR, range) and categorized into normal, borderline, and prolonged intervals according to established cutoffs. Drug–drug interactions were assessed using Micromedex, Medscape, and Drugs.com. QTc intervals were corrected using Bazett’s formula (QTc = QT/√RR), the standard method in the study hospitals, ensuring comparability with prior pharmacovigilance studies^14,15.

Statistical analysis

Continuous variables (age, QTc intervals, heart rate, and electrolyte levels) were summarized using mean ± standard deviation (SD) as well as median, interquartile range (IQR), and range to provide a complete description of the data distribution. Categorical variables were expressed as frequencies and percentages. Heart rate values were analyzed as continuous variables and reported across QTc categories (normal, borderline, prolonged). Electrolyte values were similarly reported as continuous variables and stratified by QTc category. The study was descriptive in nature, and no inferential statistical tests were conducted. Data analysis was performed using Microsoft Excel and SPSS version 22.

Result

Demographic characteristics

The study included 191 male inpatients (100%). The mean age was 37.4 ± 11.2 years, with a median of 37 years (IQR: 29–45; range: 18–65). Most participants (94.2%, n = 180) received two antipsychotic drugs, 4.7% (n = 9) received three drugs, and 1% (n = 2) received more than three drugs as presented in Table 1.

Table 1.

Patient characteristics of the study subjects.

Characteristics		Number of prescriptions, n (%)
Gender
Male	Mean ± SD	191(100%)
Characteristic	37.4 ± 11.2	Median (IQR, Range)	n (%)	Notes
Age (years)	–	37 (29–45, 18–65)	191 (100%)	Overall distribution
≤ 20	–	19 (18–20, 18–20)	12 (6.3%)	Youngest subgroup
21–30	–	25 (22–28, 21–30)	45 (23.6%)	Largest subgroup
31–40	–	35 (32–38, 31–40)	52 (27.2%)	Mid-range
41–50	–	45 (42–48, 41–50)	41 (21.5%)	Middle-aged
51–60	–	55 (52–58, 51–60)	28 (14.7%)	Older adults
≥ 61	–	62 (61–63, 61–65)	13 (6.8%)	Oldest subgroup
Number of QT-prolonging antipsychotic drugs present in a combination
Two-drug combination	180 (94.2%)
Three-drug combination	9 (4.7%)
Four-drug combination	2 (1.0%)

Clinical characteristics

None of the participants had electrolyte disturbances, were receiving diuretic therapy, or had documented cardiac disease. These exclusions ensured that QTc prolongation observed was primarily attributable to antipsychotic therapy rather than underlying medical conditions.

Prescribing patterns

A total of 395 QT-prolonging antipsychotic prescriptions were identified. The most frequently prescribed agents were risperidone, quetiapine, olanzapine, haloperidol, and chlorpromazine. Overall, moderate-risk antipsychotics accounted for the majority of prescriptions; however, strong QT-prolonging agents, particularly haloperidol and chlorpromazine, were commonly included in combination therapies. Specifically, moderate-risk drugs included risperidone (n = 128), quetiapine (n = 102), and olanzapine (n = 53), while strong-risk agents included haloperidol (n = 58) and chlorpromazine (n = 21), as shown in Table 2. Among prescriptions containing moderate-risk antipsychotics, approximately 20% also included at least one strong QT-prolonging agent.

Table 2.

Frequency of most commonly prescribed drugs.

Drug	Frequency (n)	AZCERT classification	Distribution summary
Risperidone	128	Moderate	Median 2 per patient (IQR: 1–3; range: 1–4)
Quetiapine	102	Moderate	Median 2 (IQR: 1–2; range: 1–3)
Olanzapine	53	Moderate	Median 1 (IQR: 1–2; range: 1–2)
Haloperidol	58	Strong	Median 1 (IQR: 1–2; range: 1–2)
Chlorpromazine	21	Strong	Median 1 (IQR: 1–1; range: 1–2)

*Total drug frequency = 395.

Antipsychotic doses and administration routes

To facilitate comparison across agents, prescribed antipsychotic doses were standardized using chlorpromazine equivalents (CPZeq). Both oral and parenteral formulations were included. Table 3 summarizes the frequency of exposures, CPZeq values, and administration routes.

Table 3.

Antipsychotic exposures, CPZ-eq, and routes.

Antipsychotic	Frequency (n)	Percentage (%)	CPZeq (mg)	Route of administration
Risperidone	128	32.40%	160	Oral
Quetiapine	102	25.80%	150	Oral
Haloperidol	58	14.70%	200	IM
Olanzapine	53	13.40%	200	IM
Chlorpromazine	21	5.30%	100	IM
Aripiprazole	14	3.60%	75	Oral
Clozapine	11	2.80%	500	Oral
Amisulpride	8	2.00%	200	Oral

Drug interaction severity

Among 228 identified antipsychotic drug interactions, 34.2% were classified as serious, while 65.8% required close monitoring. The most frequent high-risk combinations included haloperidol with risperidone or quetiapine (Table 4).

Table 4.

Serious QT-Prolonging Combinations.

Combination	Frequency (n)	Median QTc (ms)	IQR (ms)	Range (ms)
Haloperidol + Risperidone	31	444	441–447	432–454
Haloperidol + Quetiapine	18	444	441–447	432–447
Haloperidol + Clozapine	4	447	444–449	432–447
Chlorpromazine + Olanzapine	6	523	456–523	432–523

Continuous QTc reporting

QTc intervals were analysed as continuous variables across the entire cohort. The median QTc was 432 ms (IQR: 428–446; range: 423–523). Figure 1 illustrates the distribution of QTc values across diagnostic categories, with boxplots showing normal, borderline, and prolonged intervals. A dashed line at 450 ms marks the threshold between borderline and prolonged QTc.

Fig. 1.

Distribution of QTc intervals across diagnostic categories.

Boxplots illustrate QTc values classified as Normal, Borderline, and Prolonged. Each box shows the interquartile range (IQR), with the median marked by a horizontal line. Whiskers represent the range, and outliers are plotted as individual points. A dashed horizontal line at 450 ms indicates the threshold between borderline and prolonged QTc. This continuous approach complements the categorical summaries in Tables 4 and 5, providing clearer interpretation of QTc dispersion and highlighting the influence of antipsychotic combinations.

Table 5.

Most frequent combinations.

Combination	Frequency (n)	Median QTc (ms)	IQR (ms)	Range (ms)
Risperidone + Quetiapine	69	432	428–436	423–441
Risperidone + Haloperidol	31	444	441–447	432–454
Haloperidol + Quetiapine	18	444	441–447	432–447
Risperidone + Olanzapine	17	432	428–436	423–441

AZCERT classification of antipsychotic drugs

According to AZCERT classification, 36% (n = 69) of participants received strong–moderate combinations, 59.6% (n = 114) received moderate–moderate combinations, 4.7% (n = 9) received three-drug combinations (strong–moderate–moderate), and 1% (n = 2) received four-drug combinations (strong–moderate–moderate–strong). The most common combinations were risperidone + quetiapine (n = 69), risperidone + haloperidol (n = 31), haloperidol + quetiapine (n = 18), and risperidone + olanzapine (n = 17) (Table 6).

Table 6.

Antipsychotic drug combinations.

Drugs				Patients	Drugs	Classification of AZCERT
Drug 1	Drug2	Drug 3	Drug 4			Drug 1	Drug2
Haloperidol	Olanzapine			10	20	Strong	Moderate
Haloperidol	Clozapine			3	6	Strong	Moderate
Haloperidol	Quetiapine			11	22	Strong	Moderate
Haloperidol	Risperidone			24	48	Strong	Moderate
Haloperidol	Risperidone	Quetiapine	Chlorpromazine	2	8	Strong	Moderate
Haloperidol	Risperidone	Quetiapine		2	6	Strong	Moderate
Haloperidol	Quetiapine	Olanzapine		2	6	Strong	Moderate
Haloperidol	Risperidone	Olanzapine		3	9	Strong	Moderate
Haloperidol	Clozapine	Quetiapine		1	3	Strong	Moderate
Chlorpromazine	Risperidone			9	18	Strong	Moderate
Chlorpromazine	Clozapine			2	4	Strong	Moderate
Chlorpromazine	Quetiapine			2	4	Strong	Moderate
Chlorpromazine	Olanzapine			6	12	Strong	Moderate
Aripiprazole	Olanzapine			5	10	Moderate	Moderate
Aripiprazole	Risperidone			7	14	Moderate	Moderate
Aripiprazole	Clozapine			1	2	Moderate	Moderate
Aripiprazole	Quetiapine			1	2	Moderate	Moderate
Amisulpride	Risperidone			2	4	Moderate	Moderate
Amisulpride	Olanzapine			3	6	Moderate	Moderate
Amisulpride	Quetiapine			3	6	Moderate	Moderate
Risperidone	Quetiapine			65	130	Moderate	Moderate
Risperidone	Olanzapine			14	28	Moderate	Moderate
Olanzapine	Quetiapine			9	18	Moderate	Moderate
Clozapine	Quetiapine			3	6	Moderate	Moderate
Clozapine	Quetiapine	Olanzapine		1	3	Moderate	Moderate
Total				191	395

Torsades de pointes (TdP) risk

Out of 104 frequent drug prescriptions among 95 participants, 81% (n = 77) were classified as having a known torsades de pointes (TdP) risk, while 18.9% (n = 18) were classified as a possible risk according to CredibleMeds.org (Table 7).

Table 7.

Torsades de pointes (TdP) risks based on Crediblemeds.org.

Drug	AZCERT TdP risk	Frequency (n)	Median QTc (ms)	IQR (ms)	Range (ms)
Haloperidol	Known (List 1)	58	444	441–447	432–454
Chlorpromazine	Known (List 1)	21	523	456–523	432–523
Clozapine	Possible (List 2)	11	447	444–449	432–447
Aripiprazole	Possible (List 2)	14	432	428–436	423–441

ECG findings

Among the 47 participants who underwent ECG monitoring, they had normal electrolyte values: Potassium (K): median 3.9 mEq/L (IQR: 3.7–4.1; range: 3.5–4.3), Magnesium (Mg): median 1.7 mEq/L (IQR: 1.6–1.8; range: 1.5–1.9) and Calcium (Ca): median 8.8 mg/dL (IQR: 8.6–9.0; range: 8.4–9.2). None of the participants were receiving diuretic therapy or had documented cardiac disease, ensuring that QTc prolongation observed was primarily attributable to antipsychotic therapy. Electrolyte levels were analyzed as continuous variables, with comparisons made across QTc categories (normal, borderline, prolonged) (Table 8).

Table 8.

Electrolyte values by QTc category.

Electrolyte	Normal QTc (n = 47)	Borderline QTc (n = 5)	Prolonged QTc (n = 3)	Overall cohort
Potassium (mEq/L)	3.9 (3.7–4.1; 3.5–4.3)	3.8 (3.6–4.0; 3.5–4.1)	3.9 (3.7–4.2; 3.6–4.3)	3.9 (3.7–4.1; 3.5–4.3)
Magnesium (mEq/L)	1.7 (1.6–1.8; 1.5–1.9)	1.7 (1.6–1.8; 1.6–1.9)	1.7 (1.6–1.9; 1.5–1.9)	1.7 (1.6–1.8; 1.5–1.9)
Calcium (mg/dL)	8.8 (8.6–9.0; 8.4–9.2)	8.7 (8.5–8.9; 8.4–9.0)	8.9 (8.7–9.1; 8.6–9.2)	8.8 (8.6–9.0; 8.4–9.2)

Overall QTc distribution

The overall median QTc was 432 ms (IQR: 428–446; range: 423–523) (Table 9).

Table 9.

QTc interval findings.

QTc values (ms)	N (%)	Explanation
< 430	428 (420–430, 410–429)	Normal
430–450	441 (435–447, 432–449)	Borderline
> 450	456 (454–523, 454–523)	Prolonged

Prolonged QTc intervals (454 ms, 456 ms, and 523 ms) were most frequently observed in combinations involving haloperidol, chlorpromazine, risperidone, and quetiapine. Borderline QTc prolongation was associated with combinations such as olanzapine + risperidone, aripiprazole + clozapine, amisulpride + quetiapine, haloperidol + quetiapine, and haloperidol + clozapine (Tables 10 and 11).

Table 10.

Combinations of drugs and reported dose caused borderline QTc interval.

Combinations	Dose (max-dose/day)	Patient’s QTc value	Heart rate (bpm)
Olanzapine + Risperidone	20 mg, 4 mg	432	85 (78–92, 76–95)
Aripiprazole + Clozapine	20 mg, 100 mg	432	88 (82–94, 80–96)
Amisulpride + Quetiapine	400 mg, 150 mg	441	90 (84–96, 82–98)
Haloperidol + Quetiapine	15 mg, 300 mg	444	95 (89–101, 87–103)
Haloperidol + Clozapine	20 mg, 250 mg	447	96 (90–102, 88–104)

Table 11.

Combinations caused a prolonged QTc interval.

Combinations	Dose (max-dose/day)	Patient’s QTc value
Quetiapine + Risperidone	100mg (800 mg), 3 mg (16 mg)	454ms
Aripiprazole + Olanzapine	20mg (30 mg), 20 mg (20 mg)	456ms
Clozapine + chlorpromazine	200mg (900 mg), 100 mg (1000 mg)	523ms

Treating heart rate as a continuous variable provided additional insight into the physiological impact of antipsychotic polypharmacy. While QTc prolongation was dose-dependent, modest increases in median HR were observed in combinations involving haloperidol and clozapine, consistent with their autonomic side-effect profiles. This reinforces the importance of monitoring both QTc and HR concurrently, as tachycardia may compound arrhythmic risk.

Heart rate findings

Heart rate was analyzed as a continuous variable, providing additional insight into the physiological impact of antipsychotic polypharmacy. The overall median HR was 88 bpm (IQR: 78–96; range: 60–142). Tachycardia (> 110 bpm) was observed in 12.8% of participants, with values of 111, 112, 113, 117, 118, and 142 bpm. These findings are consistent with prior reports¹⁶ as displayed in Table 12.

Table 12.

Heart rate findings.

HR category (bpm)	Median (IQR, Range)	Notes
< 60	58 (57–59, 56–59)	Bradycardia
60–70	65 (62–68, 60–70)	Normal
71–80	76 (73–78, 71–80)	Normal
81–90	85 (83–88, 81–90)	Normal
91–100	95 (92–98, 91–100)	Normal
101–110	106 (103–108, 101–110)	Mild tachycardia
> 110	118 (112–142, 111–142)	Tachycardia

Discussion

This study demonstrates a high prevalence of QT-prolonging antipsychotic drug combinations among hospitalized psychiatric participants in Sana’a, Yemen. These findings are consistent with previous reports indicating that antipsychotic polypharmacy may increase the risk of QTc prolongation through additive or synergistic pharmacodynamic effects^12,17,18. The frequent prescription of strong QT-prolonging agents, particularly haloperidol and chlorpromazine, often in combination with moderate-risk antipsychotics, underscores the clinical relevance of this issue in routine psychiatric practice.

In this research, 6.4% of participants exhibited QTc prolongation, a figure that, although modest, represents a higher prevalence compared to baseline rates in populations without antipsychotic exposure, where QTc prolongation is typically reported at 1–2% in general emergency department cohorts and rarely exceeds 5% in medically ill patients without psychotropic therapy^19,20. This contrast highlights the additive risk posed by antipsychotic polypharmacy in psychiatric inpatients.

The results align with existing literature on QT prolongation risk factors in psychiatric populations and emphasize the importance of careful monitoring and management of QTc abnormalities in hospitalized participants. Although many of the antipsychotic combinations identified in this study are not formally contraindicated according to AZCERT classification and may be clinically necessary in certain circumstances, their use warrants heightened vigilance. Participants not receiving QT-prolonging combinations demonstrated higher Global Assessment of Functioning (GAF) scores at both admission and discharge compared with those receiving such combinations, suggesting a potential association between polypharmacy and poorer clinical status^21–23.

Haloperidol and chlorpromazine were confirmed as strong QT-prolonging agents, consistent with their established risk profiles. Frequently prescribed combinations involving moderate-risk agents, such as risperidone and quetiapine, further highlight the need for individualized risk assessment and close monitoring. QTc prolongation was dose-dependent, and higher chlorpromazine equivalent (CPZeq) doses were associated with greater QTc prolongation, particularly in strong-risk combinations. Standardizing doses in CPZeq allowed meaningful cross-drug comparisons, while specifying the route of administration provided important pharmacokinetic context, as parenteral formulations (e.g., intramuscular haloperidol or olanzapine) may produce higher peak plasma concentrations and transient QTc changes compared to oral dosing¹¹.

Because heart rate can be influenced by multiple factors beyond antipsychotic medication (e.g., anxiety, physical activity, hydration status), ECGs were recorded under standardized resting conditions and verified by a cardiologist. This strengthens the reliability of the observed median heart rate of 88 bpm (IQR: 78–96; range: 60–142). Electrocardiographic findings revealed varying degrees of QTc prolongation, illustrating the potential impact of antipsychotic polypharmacy on cardiac repolarization. Importantly, 30.3% of identified antipsychotic combinations were classified as serious interactions, indicating the need for prompt clinical intervention to reduce adverse outcomes.

Electrolyte values were consistently within normal ranges, supporting the interpretation that QTc prolongation observed was primarily drug-related rather than secondary to electrolyte imbalance. Based on these findings, routine baseline and follow-up ECG assessments, in addition to electrolyte monitoring, are strongly recommended. In high-risk participants, ECG monitoring should continue until steady-state concentrations of QT-prolonging drugs are achieved—approximately five half-lives after treatment initiation—followed by monthly ECGs during the first six months and subsequently every six to twelve months, as recommended in previous guidelines. The limited availability of ECG monitoring observed in this study highlights a significant gap in clinical practice, particularly in resource-limited settings.

Our findings (6.4% QTc prolongation; 10.6% borderline QTc intervals) are consistent with international reports. For example, Ansermot et al. reported QTc prolongation in 7.6% of Swiss psychiatric inpatients²⁴. while Salvati et al. found 11.6% in acute psychiatric inpatients in Italy²⁵. Taken together, these studies demonstrate that QTc prolongation is a clinically relevant issue across psychiatric inpatient settings worldwide. Our results from Yemen align with these prevalence rates, reinforcing the global importance of systematic ECG monitoring and careful antipsychotic prescribing practices.

Several limitations should be considered. The retrospective design limits causal inference, and ECG data were available for only a subset of participants, potentially underestimating the true prevalence of QTc prolongation. The inclusion of only male participants restricts generalizability to female populations. Clinical outcomes such as documented torsades de pointes (TdP) or other arrhythmic events were not assessed. Bazett’s formula was used to correct QT intervals, but it may overestimate QTc at high heart rates and underestimate at low heart rates. Although alternative correction methods (e.g., Fridericia’s, Framingham’s) may improve accuracy, Bazett’s formula remains the most widely applied in routine hospital ECG reporting and pharmacovigilance studies, ensuring methodological consistency.

Because inclusion was restricted to patients already receiving QT-prolonging antipsychotic polypharmacy, our findings describe risk characteristics within this subgroup rather than the overall prevalence of QT-prolonging antipsychotic use in psychiatric inpatients. Future studies should include all admitted patients to provide a more comprehensive prevalence estimate. Additionally, other psychotropic medications such as antidepressants may contribute to QTc prolongation. Recording and analyzing these concomitant therapies is essential, as they can exert additive effects on cardiac repolarization.

This study was limited by the absence of a comparator group of psychiatric inpatients not receiving QT-prolonging antipsychotic polypharmacy, the small number of patients with ECG data (47, of whom only three exhibited QTc prolongation and none had TdP), the retrospective design and restriction to male participants, and the lack of systematic screening for other potential confounders such as renal or hepatic disease or concurrent use of antibiotics, antifungals, or methadone.

Conclusion

This study highlights the presence of QTc abnormalities among psychiatric inpatients already receiving QT-prolonging antipsychotic polypharmacy in Sana’a, Yemen. Although no cases of torsades de pointes (TdP) were observed, 6.4% of participants exhibited QTc prolongation and 10.6% had borderline QTc intervals, underscoring the importance of systematic ECG monitoring and cautious prescribing in this high-risk subgroup. The concurrent use of multiple QT-prolonging antipsychotics was common, with moderate–moderate combinations accounting for the majority of prescriptions. The most frequently prescribed combinations were risperidone plus quetiapine and risperidone plus haloperidol. These findings emphasize that polypharmacy involving QT-prolonging agents warrants careful benefit–risk evaluation, particularly in resource-limited settings where monitoring capacity is constrained. Participants with additional risk factors for QTc prolongation require closer clinical surveillance, especially when antipsychotic polypharmacy is unavoidable. Careful selection of drug combinations, routine ECG and electrolyte monitoring, and increased clinician awareness are essential to reduce preventable cardiac complications and improve medication safety in psychiatric practice. Future studies should include comparator groups of psychiatric inpatients not exposed to QT-prolonging antipsychotics and expand the scope to incorporate other psychotropic medications, such as antidepressants, to better quantify the incremental risk of QTc prolongation and TdP.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

Wafa M. Al-Madhagi: Conceptualization, Formal analysis, Methodology, Investigation, Project administration, Supervision, Writing – original draft, Writing – review and editing, Software; Olla Sharhan: Conceptualization, Formal analysis, Methodology, Writing – original draft, Writing – review and editing, Software; Mohammed A. Al-Khawlani: Formal analysis, Methodology, Investigation, Software, Writing – original draft; Rayan N. Al-Obydi: Formal analysis, Methodology, Investigation, Project administration, Software. Writing – original draft; Tawheeb A. Ali: Conceptualization, Investigation, Software, Writing – original draft; Abdulrahman A. Abdulrahman: Formal analysis, Methodology, Investigation, Project administration, Software. Writing – original draft; Osama A. Dabwan: Formal analysis, Methodology, Investigation, Project administration, Software. Writing – original draft; Ammar AL-Farga: Writing – original draft.

Data availability

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Declarations

Competing interests

The authors declare no competing interests.

Ethical approval and consent to participate

Ethical approval was obtained from the Research Committee of Al-Nasser University (Code: NU-RECM2309). Written informed consent was obtained from all participants.