---
title: "Prevalence, Severity and Predictors of Antipsychotic-Related Adverse Drug Reactions in a Ugandan R"
id: "plos-one-14-prevalence-severity-and-predictors-of-antipsychotic-related-adverse-drug"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-14-prevalence-severity-and-predictors-of-antipsychotic-related-adverse-drug"
content_type: "clinical_feed_article"
specialty: "General"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356000"
published_at: "2026-08-13T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Prevalence, Severity and Predictors of Antipsychotic-Related Adverse Drug Reactions in a Ugandan R
## Provenance & Clinical Metadata
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- **Specialty:** [General](https://medichelpline.com/clinical-feed/general.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356000)
- **Published At:** 2026-08-13T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This cross-sectional study at Mbarara Regional Referral Hospital (MRRH) in Uganda enrolled 415 adult outpatients on antipsychotics between March and May 2025 to assess **antipsychotic-related adverse drug reactions (ADRs)**. - Overall, 61.7% (256/415) of participants reported at least one ADR; sedation was the most commonly reported symptom (31.3%). - Fifteen distinct ADRs were documented; 12 of these (80%) were classified as moderate in severity using the modified Hartwig and Siegel scale. - Multivariable logistic regression identified three independent predictors of ADRs: being separated from a spouse (AOR 2.01, 95% CI 1.08–3.77, p = 0.029), a diagnosis of **bipolar disorder** (AOR 2.09, 95% CI 1.07–4.07, p = 0.031), and concomitant administration of both intramuscular (IM) and oral antipsychotics (AOR 1.95, 95% CI 1.03–3.70, p = 0.041). - The mean participant age was 38 years. Inclusion criteria were age ≥18, a psychotic disorder diagnosis, and at least one month of antipsychotic therapy; consecutive sampling was used. - Statistical analyses were performed in STATA v17; descriptive stats and multivariable logistic regression were reported. ADR severity was graded by the modified Hartwig and Siegel scale. - Authors conclude that more than six in ten patients experienced ADRs, most of moderate severity, and recommend strengthened monitoring and preventive strategies with emphasis on high-risk groups and integration of clinical pharmacists into psychiatric care teams. - The study data and supporting information are available in the paper; funding was provided by King Khalid University. No competing interests were declared.
## Clinical Analysis & Structured Key Points
Prevalence, severity and predictors of Antipsychotic-Related Adverse Drug Reactions at the Psychiatry Clinic of a Regional Referral Hospital in Uganda | PLOS One Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Article Authors Metrics Comments Media Coverage Reader Comments Figures Figures Abstract Background Adverse drug reactions (ADRs) are associated with hospitalization, increased healthcare cost, morbidity and mortality. This study aimed to investigate the prevalence, severity and associated factors of ADRs among patients taking antipsychotics at Mbarara Regional Referral Hospital (MRRH). Method A cross-sectional study was conducted among patients taking antipsychotics at the psychiatric clinic from March to May 2025. Consecutive sampling was employed whereby all eligible patients attending the psychiatric clinic during the study period were recruited until the required sample size was attained. All patients aged 18 years and above, diagnosed with a psychotic disorder, and who had received an antipsychotic for at least the previous one month were interviewed. STATA version 17 was used for statistical data analysis. Descriptive statistics were presented as mean and standard deviation or median and interquartile ranges. ADRs were analyzed for severity using the modified Hartwig and Siegel scale. We run multivariable logistic regression analysis to determine factors associated with ADRs. Results A total of 415 participants were included in the study with a mean age of 38. Fifteen ADRs were commonly reported among patients taking antipsychotics. More than half of the participants (256/415, 61.70%) experienced at least one ADR, with sedation being the most frequent (31.3%). Of the reported ADRs, 12/15 (80%) were moderate in severity. Separation from spouses (AOR = 2.01, 95% CI [1.08–3.77], p = 0.029), diagnosed with bipolar disorder (AOR = 2.09, 95% CI [1.07–4.07], p = 0.031), and co-administering both IM & oral antipsychotic (AOR = 1.95, 95% CI [1.03–3.70], p = 0.041) were significantly associated with ADRs. Conclusion The current study showed that over 6 in 10 participants taking antipsychotics experienced at least one ADR, the majority of which were moderate in severity. Separation from a spouse, bipolar disorder, concomitant use of oral and intramascular antipsychotics were independently associated with ADRs. These findings highlight the need for strengthen monitoring and preventive strategies, particularly among high-risk patients taking antipsychotics. Integration of clinical pharmacists into the psychiatry care teams may further enhance ADR detection, monitoring and management. Citation: Tumwebaza JM, Bukke SPN, Narapureddy BR, Kabera RM, Sebisaalu J, Abubakar A, et al. (2026) Prevalence, severity and predictors of Antipsychotic-Related Adverse Drug Reactions at the Psychiatry Clinic of a Regional Referral Hospital in Uganda. PLoS One 21(8): e0356000. https://doi.org/10.1371/journal.pone.0356000 Editor: Joseph Olusesan Fadare, Ekiti State University College of Medicine, NIGERIA Received: March 7, 2026; Accepted: July 28, 2026; Published: August 13, 2026 Copyright: © 2026 Tumwebaza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: All relevant data are within the paper and its Supporting Information files. Funding: This study was financially supported by the Deanship of Research and Graduate Studies at King Khalid University [ https://www.kku.edu.sa] in the form of a Large Research Project grant (RGP2/639/46). No additional external funding was received for this study. Competing interests: The authors have declared that no competing interests exist. Abbreviations: ADR, Adverse Drug Reaction; AOR, Adjusted odds ratios; CI, Confidence interval; FGA, First Generation Antipsychotics; HIV/AIDS, Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome; IM, Intramuscular; MRRH, Mbarara Regional Referral Hospital; MUST, Mbarara University of Science and Technology; TGA, First Generation Antipsychotics; SGA, Second Generation Antipsychotics; SSA, Sub-Saharan Africa; WHO, World Health Organization Introduction Psychosis is a clinical syndrome characterized by hallucinations, delusions, grossly disorganized behavior and disorganized speech [ 1 ]. Globally, the prevalence of psychosis has been increasing by over 65% from 1990–2019 [ 2 ]. In sub-Saharan Africa, a scooping review revealed that the lifetime prevalence of psychosis varies from 1.0% to 4.4% [ 3 ]. In Uganda, a retrospective study carried out in Butabika National Referral Hospital (BNRH) in 2018, showed a prevalence of psychosis at 62.7% [ 4 ]. Patients with psychosis require antipsychotic medications to manage their symptoms and restore their functionality. Antipsychotic drugs form a group of treatments primarily aimed at managing mental health conditions such as schizophrenia, anxiety and other disorders presenting with psychotic symptoms [ 5 – 7 ]. Antipsychotics are classified into first generation antipsychotics (FGAs), second generation antipsychotics (SGAs) [ 8 ] and third generation antipsychotics (TGAs) [ 8 , 9 ]. FGA for example haloperidol, trifluoperazine and chlorpromazine block dopamine (D2) receptors of dopaminergic neurons. SGAs primarily block serotonin receptors (5-HT2A) and D2 receptors and they include clozapine, quetiapine, olanzapine, and risperidone [ 8 ]. TGAs act by mainly partially agonizing D2 and 5HT1A receptors with examples including aripiprazole, cariprazine and brexpiprazole [ 10 ]. Adverse drug reactions have been observed to be common among most patients with psychosis taking antipsychotic medication. The World Health Organization (WHO) defines an adverse drug reaction (ADR) as any harmful, unintended response to a medicine that occurs at doses normally used in man for the prevention, diagnosis or treatment of disease, or for modifying physiological function [ 11 ]. Globally, the prevalence of ADRs among patients taking antipsychotics has not been estimated in meta-analysis, however individual studies conducted in India and France have revealed an ADR prevalence of 5.67% and 8.3% respectively [ 12 , 13 ]. In sub-Saharan Africa, a meta-analysis revealed that the prevalence of ADRs among patients taking anti psychotics is at 51% [ 14 ]. In Uganda, and at Mbarara in particular, a study conducted among hospitalized patients revealed the prevalence of ADR at 48.9% [ 15 ]. No study, however, has been conducted to investigate ADRs among patients taking antipsychotics at psychiatric unit of MRRH. Examples of ADRs include sedation, weight gain, sexual dysfunction, tardive dyskinesia, akathisia, muscle stiffness, hyperglycemia, vomiting, dry mouth and slurred speech. Factors that contribute to the development of ADRs can be drug related such as type of antipsychotic, other non-antipsychotic, polypharmacy, frequency, route of administration [ 16 , 17 ]. Patient related factors such as age, gender, level of education, marital status, occupation, income status and perceived social support may also lead to development of ADRs [ 18 , 19 ]. The other factors that play a role in the occurrence of ADRs are Illness related factors which include type of psychiatric disorder, duration with disorder, number of comorbid conditions, type of comorbid condition and number of in-hospital admission [ 20 ]. Age and polypharmacy are the most common predictors in development of ADR among patients taking antipsychotics [ 19 , 21 , 22 ]. ADRs contribute significantly to increased hospitalization [ 23 ] and medical costs [ 24 ]. A reported study in England showed that ADRs have an estimated admission cost of £490 716 which when extrapolated nationally, totals up to 2.21 billion annually [ 25 ]. ADRs also lead to therapy non-adherence and/or discontinuation [ 26 ] morbidity and mortality [ 27 , 28 ]. In USA, estimates indicate that ADRs rank as the fourth major contributor to mortality [ 29 ]. Despite the recognized global burden of antipsychotic-related ADRs, there remains a critical gag in Uganda, particularly in southwestern Uganda where Mbarara Regional Referral Hospital (MRRH) serves a population of over four million people. While previous studies at MRRH have examined ADRs among hospitalized patients with general medical conditions [ 15 , 30 ], none have specifically focused on antipsychotic-related ADRs among psychiatric outpatients. This gap is concerning given that MRRH’s psychiatric clinic serves approximately 100 patients weekly and over 1,200 new patients annually, with over 90% of outpatients prescribe antipsychotics. Furthermore, the patient population at MRRH presents unique risk factors that have not been systematically studied. These include high utilization of first-generation antipsychotics (FGAs) due to government supply and affordability constraints, high prevalence of substance use disorders requiring higher antipsychotic doses and limited pharmacovigilance infrastructure. This study, therefore, was designed to fill this evidence gap by instigating the prevalence, severity, and associated factors of ADRs among patients taking antipsychotics at the psychiatry clinic of MRRH. The findings will provide the foundational evidence needed to inform the development of targeted monitoring protocols, guide clinical decision-making regarding antipsychotic selections and dosing, support the integration of clinical pharmacists into psychiatry teams, and strengthen pharmacovigilance activities at the facility level. Methods Study design and setting This was a cross-sectional study conducted among outpatients taking antipsychotics at Mbarara Regional Referral Hospital Psychiatric Unit between March 2025 to May 2025. MRRH, a 600-bed tertiary hospital, serves as a key referral hospital in southwestern Uganda, 270 kilometers from Kampala. It caters to a population exceeding four (4) million residents across districts including Mbarara, Bushenyi, Ntungamo, Kiruhura, Ibanda, Buhweju, Rubirizi, Mitooma, and Isingiro. Furthermore, it also provides care to patients from Kabale, Masaka, Fort Portal, and even from neighboring countries like Rwanda. The MRRH Psychiatric Clinic operates within the psychiatric ward on Tuesdays and Wednesdays. Normally, 100 patients are registered per week and approximately 1200 new patients annually. The clinic boasts a comprehensive team of mental health professionals, including psychiatrists (3), occupational therapists (3), counselor (1), social workers (2), psychiatric clinical officers (3), psychiatric nurses (3) and psychiatry residents (15). Eligibility criteria Inclusion criteria. We enrolled all patients at psychiatry outpatient clinic of MRRH, aged 18 years and above, who were diagnosed with a psychotic disorder, and currently taking antipsychotics for at least the past 1 month and who were willing to provide written informed consent for participation in the study. Exclusion criteria. We excluded all patients with active psychotic symptoms. Sample size determination The sample size was calculated using Kish-Leslie formular; n = Z 2 P(1-P)/d 2 [ 31 ]. The prevalence of ADR among patients taking antipsychotics in a previous study in India was 43.5% [ 32 ]. Since the study settings were similar, we used 43.5% as the expected prevalence (p) of ADR among patients taking antipsychotics, with a 0.05 significance (alpha) level at a 95% confidence interval (CI). p = 43.5% d = 0.05 z = 1.96 (at CI of 95%). Applying the formula mentioned above, the number of participants included in the study was = 378. A 10% non-response rate was added: = (10%*378) = 38. The target sample size that was interviewed = (378 + 38) = 415 participants. A review of the number of patients attending the psychiatry clinic was conducted and on average 400 psychiatry patients are seen at the clinic per month. Sampling technique A Consecutive sampling method was used until the sample size was attained, throughout the investigation. The procedure of gathering data took three months to complete to obtain the necessary sample size. Study variables Dependent variable. Adverse drug reactions were the primary outcome of this study. They included weight gain, akathisia, dry mouth, tremors, sedation, tardive dyskinesia, hyperglycemia, nausea and vomiting, increased appetite, slurred speech, constipation, skin rush, blurred vision, drowsiness, and dystonia. For the assessment of weight gain and hyperglycemia, baseline measurements were established using documented medical records or, where unavailable, structured patient/caregiver interviews. Baseline weight was defined as the patient’s body weight documented within the first week of initiating the current antipsychotic regimen or the earliest recorded weight prior to antipsychotic initiation. Weight gain was classified as an increase of 7% or more from this baseline weight, consistent with established clinical thresholds for antipsychotic-induced weight gain. For hyperglycemia, baseline glycemic status was determined by reviewing medical records for prior diagnoses of diabetes mellitus or documented elevated blood glucose prior to antipsychotic initiation, supplemented by patient and caregiver interviews to confirm the absence of pre-existing hyperglycemia. Newly elevated RBS was defined as a random blood sugar >180 mg/dL, and newly elevated FBS as a fasting blood sugar >100 mg/dL, occurring after antipsychotic initiation without prior documented hyperglycemia. Operational definitions of ADRs assessed. All 15 ADR types were assessed using standardized operational definitions derived from established pharmacovigilance guidelines and clinical assessment scales. Sedation was defined as subjective excessive sleepiness or reduced alertness interfering with daily functioning. Drowsiness was defined as abnormal sleepiness during waking hours. Tremors were defined as involuntary rhythmic oscillatory movements assessed through neurological examination. Weight gain was defined as an increase of ≥7% from baseline body weight established within the first week of antipsychotic initiation. Dry mouth was defined as subjective oral dryness attributed to antipsychotic therapy. Akathisia was defined as subjective inner restlessness with observable motor phenomena (fidgeting, pacing, inability to sit/stand still). Tardive dyskinesia was defined as new repetitive involuntary movements primarily affecting the oro-bucco-lingual area, developing after ≥3 months of antipsychotic exposure. Hyperglycemia was defined as new-onset elevation in blood glucose (RBS > 180 mg/dL or FBS > 100 mg/dL) occurring after antipsychotic initiation without prior documented diabetes mellitus. Nausea and vomiting were defined as subjective urge to vomit with or without expulsion of gastric contents. Increased appetite was defined as perceived increase in hunger beyond usual patterns. Slurred speech was defined as impaired articulation observed during clinical interviews. Constipation was defined as reduced bowel frequency (<3 per week) with difficulty passing stools. Skin rash was defined as new-onset cutaneous eruption excluding pre-existing dermatological conditions. Blurred vision was defined as subjective reduction in visual clarity. Dystonia was defined as sustained or intermittent involuntary muscle contractions causing abnormal postures or movements, assessed through clinical observation. Each ADR was confirmed by both the principal investigator and a resident psychiatrist before classification. Independent variables. The independent variables were factors that have been reported in the literature to be associated with ADRs among patients taking antipsychotics. These included socio-demographic characteristics, illness related factors and medication related factors [ 17 , 19 – 21 , 33 ]. Socio-demographic factors included age, gender, level of education, employment status, income status, marital status, perceived social support. Illness related factors included type of psychiatric disorder, duration with the disorder, number of comorbid conditions, type of the comorbid condition, number of in-patient hospital admission. The medication related factors included type of antipsychotic, route of administration, counselling on ADRs. Data collection tool, procedure, management, and quality control The data collection instrument was a structured, interviewer-administered questionnaire comprising six distinct modules: (1) Socio-demographic characteristics (age, gender, education, marital status, employment, income), (2) Illness-related factors (type of psychiatric disorder, duration, comorbidities, hospital admissions), (3) Medication-related factors (antipsychotic type, route, duration, counselling, concurrent medications), (4) ADR profile assessment (presence of 15 specific ADRs with clinical criteria, onset timing, severity, causality, and preventability using Naranjo, Hartwig-Siegel, and Schumock-Thornton scales), and (6) Perceived social support (Multidimensional Scale of Perceived Social Support – MSPSS). Additionally, clinical assessments including weight measurement and blood glucose monitoring were performed where feasible. Perceived social support of the participants was assessed utilizing the Multidimensional Scale of Perceived Social Support (MSPSS) [ 34 ]. ADR was defined according to WHO’s definition of ADR as presented above [ 11 ]. The established adverse reaction of each drug was assessed using Up-To-Date (2024) version 3.66.4. ADRs were initially suspected when there was a relationship between drug administration and the onset and progression of the adverse reaction, after excluding other possible causes. Naranjo adverse drug reaction probability scale, a standard causality assessment tool, was used to determine the probability of ADR [ 35 ]. Severity of ADR was assessed using modified Hartwig and Siegel severity assessment Scale [ 36 ]. Preventability of ADR was evaluated using Schumock and Thornton preventability scale [ 37 ]. The Naranjo Probability Scale, Modified Hartwig and Siegel Severity Scale, and Schumock and Thornton Preventability Scale are well-established frameworks with high validity and reliability in pharmacovigilance [ 38 ]. Data collection followed a structured workflow with clearly defined personnel roles. The research team comprised the Principal Investigator (PI – a Clinical Pharmacist Resident with Master of Pharmacy in Clinical Pharmacy training), a Research Assistant (Psychiatry Resident), and a Psychiatric Nurse. All team members received standardized training on ethical procedures, data collection techniques, and ADR assessment using validated scales. The data collection process involved: (1) screening and recruitment of eligible participants on clinic days (Tuesdays and Wednesdays); (2) obtaining written informed consent; (3) face-to-face interviews using a structured questionnaire with six modules (socio-demographics, illness factors, medication factors, ADR profiles, and social support); (4) medical record review for clinical and medication history; (5) clinical assessments including weight measurement, blood glucose monitoring (where feasible), and neurological examination for movement disorders. For ADR assessment, suspected ADRs were initially identified by the PI based on pharmacological knowledge and patient history. Each suspected ADR was then jointly confirmed by the PI and the Resident Psychiatrist, considering temporal relationships, clinical presentation, and exclusion of other causes. Once confirmed, the Naranjo Adverse Drug Reaction Probability Scale was applied jointly to assess causality, the Modified Hartwig and Siegel Scale to classify severity, and the Schumock and Thornt
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