Lithium-associated adverse drug reactions: characteristics, possible etiologies, and preventability

Introduction Lithium is an effective mood stabilizer with a narrow therapeutic range. Lithium-associated adverse drug reactions affect multiple body systems and can result in significant morbidity and death. In this study, we aim to determine the severity, outcomes, and preventability of lithium-associated adverse drug reactions.Methods We conducted a retrospective cross-sectional study of lithium-associated adverse drug reaction patients, who visited a tertiary-care university hospital between 2012 and 2022, and had lithium levels beyond the therapeutic range. Patients with the following conditions were excluded: intentional ingestion, incomplete medical records, and no lithium-associated adverse drug reaction. Data were collected from the hospital’s database and reviewed by three independent reviewers. Adverse drug reaction preventability was assessed using a Likert scale (non-preventable: 1–3, preventable: 4–6). Characteristics, clinical presentation, and severity of adverse drug reactions were analyzed.Results A total of 91 patients were included: 32 (35.2%) and 59 (64.8%) in the non-preventable and preventable groups, respectively. The patients in the preventable group were older (P = 0.017), had lower estimated glomerular filtration rates (eGFRs; P <0.001), and had more comorbidities (diabetes, hypertension, and dyslipidemia; P = 0.004). The patients primarily presented in the outpatient department (63.74%) and had acute-on-chronic onset (45.1%). Preventable adverse drug reactions were linked to delayed monitoring (55.9%), dehydration (39.0%), drug interactions (17.0%), previous episode of high lithium levels within three years (13.6%), and clinical underdetection (11.9%). The most common cause of non-preventable adverse drug reactions was lithium dose adjustment (37.5%). Neurological effects were predominant. There were significantly more moderate (47.5%) and severe (5.1%) cases in the preventable group than non-preventable group (18.8% moderate, and no severe case; P = 0.006).Discussion The majority of lithium-associated adverse drug reactions are preventable and linked to greater severity. Targeted interventions should focus on older patients with renal impairment, or comorbidities. Clinical strategies should prioritize regular lithium monitoring, proactive drug-interaction screening, and patient education regarding hydration to reduce these preventable adverse drug reactions.Conclusion Our findings indicate that most lithium-associated adverse drug reactions are preventable and influenced by several factors (e.g., age, eGFR, comorbidities, drug interactions, and dehydration) and that preventable adverse drug reactions result in more severe outcomes.