In a groundbreaking case-control study conducted at psychiatry units in Mekelle, Northern Ethiopia, researchers have shed new light on the predictors of extrapyramidal side effects (EPS) among patients undergoing antipsychotic treatment. This investigation, published in the esteemed journal BMC Psychiatry in 2025, delves deep into the clinical and behavioral factors that potentiate movement disorders, illuminating crucial elements that could transform how mental health professionals manage side effects related to antipsychotic drugs.
Schizophrenia, a neuropsychiatric disorder that impacts approximately 1% of the global population, fundamentally disrupts cognition, behavior, and emotional regulation. Antipsychotic medications, particularly first-generation agents, have long been the cornerstone of schizophrenia treatment, balancing symptom relief against a notorious risk profile—chief among them are extrapyramidal side effects. EPS comprises a spectrum of movement abnormalities, including tremors, rigidity, bradykinesia, and tardive dyskinesia, often leading to substantial patient distress and decreased treatment adherence.
The study employed an unmatched case-control design involving 201 participants—67 cases exhibiting EPS and 134 controls without such symptoms. Utilizing a rigorous systematic random sampling method, researchers meticulously identified patients currently taking antipsychotic medication, ensuring robust data collection. To quantify EPS severity, validated scales including the Simpson-Angus Scale, the Abnormal Involuntary Movement Scale (AIMS), and the Barnes Akathisia Rating Scale (BARS) were used, enabling precise clinical characterization.
Analytical scrutiny was carried out through bivariate and multivariate logistic regression using SPSS version 22. This statistical framework allowed the determination of independent predictors with high confidence. Intriguingly, the study unmasked a constellation of modifiable and non-modifiable factors significantly associated with the emergence of EPS. These insights hold promise for tailoring interventions that mitigate risks and enhance quality of life for patients on antipsychotic therapies.
Counterintuitively, female patients exhibited a dramatically reduced likelihood of developing EPS, with an adjusted odds ratio (AOR) of 0.14, suggesting underlying biological or hormonal influences that merit further exploration. Conversely, single individuals demonstrated an increased risk (AOR = 3.08), which may reflect social determinants such as support systems or stress levels that impact neuropsychiatric vulnerability.
The interplay between perceived stigma and EPS was equally compelling. Those reporting higher stigma perceptions paradoxically had lower odds of side effects (AOR = 0.165). This phenomenon raises questions about the psychosocial frameworks influencing patient reporting and healthcare engagement, pointing to the complex biopsychosocial underpinnings of antipsychotic side effects.
A history of prior mental illness conferred a markedly heightened risk of EPS (AOR = 6.3), underlining the cumulative burden of psychiatric morbidity on neurological function. This finding stresses the importance of early intervention and vigilant monitoring in patients with protracted psychiatric histories to forestall debilitating motor symptoms.
The pharmacological regimen emerged as a critical determinant of EPS. Patients on combined first-generation antipsychotic drugs had a substantially lower risk (AOR = 0.095), potentially reflecting dose-related effects or differential neuroleptic potency. However, this finding also implies the need for careful assessment of polypharmacy, with an emphasis on optimizing drug combinations to reduce extrapyramidal toxicity without compromising therapeutic efficacy.
Substance use, notably Khat chewing—a prevalent practice in the Horn of Africa—and recent alcohol intake, were independently linked with increased EPS risk. Khat use showed an AOR of 4.03, while alcohol consumption bore a similar association (AOR = 6.2). These substances may exacerbate neurochemical imbalances or interact adversely with antipsychotics, suggesting that behavioral counseling and substance use interventions should be integral to mental health care protocols in this region.
The study’s findings carry profound clinical implications. Psychiatric professionals are urged to incorporate systematic assessments of these identified predictors into routine evaluations, to preemptively identify at-risk individuals. The nuanced understanding of how sociodemographic factors, substance use behaviors, and pharmacologic profiles intersect to influence EPS risk offers a blueprint for personalized medicine approaches.
Management strategies should prioritize reducing exposure to high-risk antipsychotic regimens, integrating psychosocial support to address stigma and relationship status, and deploying targeted substance cessation programs. This holistic strategy aligns with contemporary shifts in psychiatry toward patient-centered care that emphasizes both medical and psychosocial determinants of health.
Moreover, this work reflects the importance of culturally and regionally contextualized research. The unique lifestyle factors prevalent in Northern Ethiopia, such as Khat chewing, are rarely captured in global psychiatric studies. Incorporating such region-specific variables enriches the global understanding of EPS, advocating for diverse geographic representation in psychiatric research.
Future studies will need to dissect the biological mechanisms underpinning these associations, possibly exploring genetic polymorphisms, neuroinflammation pathways, and neurochemical receptor sensitivities that differ by sex and substance exposure. Such translational research could yield biomarkers predictive of EPS susceptibility, revolutionizing preventive psychiatry.
In conclusion, this seminal research from Mekelle Psychiatry units offers a detailed map of extrapyramidal side effect predictors, combining clinical rigor with culturally nuanced insights. Its revelations about gender differences, social factors, pharmacological strategies, and substance use create a multifaceted narrative crucial for advancing schizophrenia management globally. The integration of these findings into clinical practice promises to enhance patient outcomes, reduce side effect burdens, and promote adherence to essential antipsychotic therapies.
Subject of Research: Predictors of extrapyramidal side effects among patients taking antipsychotic medication
Article Title: Predictors of extrapyramidal side effects among patients taking antipsychotic medication at Mekelle psychiatry units, Northern Ethiopia, 2023: unmatched case-control study
Article References:
Gebru, W.A., Asfaw, G.K., Berhe, K.T. et al. Predictors of extrapyramidal side effects among patients taking antipsychotic medication at Mekelle psychiatry units, Northern Ethiopia, 2023: unmatched case-control study. BMC Psychiatry 25, 837 (2025). https://doi.org/10.1186/s12888-025-07202-7
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