Lithium: A review of its adverse effects, toxicity and discontinuation

Lithium remains the gold standard treatment for bipolar disorder after over 60 years of clinical use, with expanding therapeutic applications in neurodegenerative conditions. Despite its proven efficacy, lithium presents unique challenges due to its narrow therapeutic window and complex side effect profile. This comprehensive review synthesizes current evidence on lithium toxicity, adverse effects, and discontinuation management from 2019-2025, incorporating significant earlier studies. Lithium demonstrates efficacy in treating bipolar disorder, with approximately two-thirds of patients experiencing clinically significant improvement and more than half achieving remission. Additionally, it shows promising anti-suicidal properties, though careful management is required when discontinuing the medication. The manuscript examines lithium's pharmacokinetics and toxicity classification (acute, acute-on-chronic, and chronic), with detailed analysis of system-specific adverse effects including renal, neurological, cardiovascular, and endocrine manifestations. Risk factors for toxicity include age, comorbidities, drug interactions (particularly with NSAIDs, diuretics, and ACE inhibitors), and environmental factors. The review provides evidence-based recommendations for diagnostic evaluation, management protocols for toxicity cases, and monitoring guidelines to minimize adverse effects. Special attention is given to lithium discontinuation, highlighting the importance of gradual tapering to prevent relapse and withdrawal syndromes. For patients requiring alternative medication, the manuscript offers guidance on transition strategies to maintain mood stability. This comprehensive review aims to provide clinicians with practical guidance to optimize lithium therapy while minimizing risks.