Unintentional Lithium Toxicity in Patients With Bipolar Disorder: A Literature Review of Case Reports

Unintentional lithium toxicity is a clinically relevant and potentially underrecognized complication in patients with bipolar disorder receiving long-term maintenance therapy. This literature review aimed to synthesize published case reports of unintentional lithium toxicity in bipolar disorder, focusing on recurrent clinical manifestations, contributing risk factors, and the relationship between clinical toxicity and serum lithium concentrations.

Case reports published between 2009 and 2024 were identified through PubMed and the Virtual Health Library using the terms lithium, intoxication, and bipolar disorder. Adult patients with bipolar disorder experiencing unintentional lithium toxicity were included. Demographic data, clinical presentation, serum lithium concentrations, renal function, comorbidities, duration of lithium therapy, and concomitant medications were extracted and descriptively analyzed.

Twenty-one case reports were included. Most patients were female (76.2%), with a mean age of 61 years. Neurological manifestations predominated, with tremor being the most frequent symptom (61.9%), followed by altered mental status (42.9%), decreased level of consciousness (38.1%), and gait disturbance or ataxia (38.1%). Speech disturbances, myoclonus, and gastrointestinal symptoms (nausea, vomiting, or diarrhea) were also commonly reported. Serum lithium concentrations exceeded 1.5 mmol/L in 81.0% of cases, with most classified as severe intoxication; however, clinically significant toxicity also occurred at therapeutic or near-therapeutic levels. Renal dysfunction was frequent, with elevated serum creatinine reported in approximately two-thirds of patients. Polypharmacy was common, particularly involving antipsychotics, diuretics, and antihypertensive agents. The most frequent lithium dose was 600 mg/day, and prolonged exposure (>10 years) occurred in nearly one-third of cases.

Unintentional lithium toxicity presents with heterogeneous and predominantly neurological manifestations and may occur despite therapeutic serum lithium concentrations. Comprehensive clinical assessment, including neurological examination, renal function evaluation, and medication review, is essential to ensure safer long-term lithium use.