Lithium-related neurotoxicity despite serum concentrations in the therapeutic range: risk factors and diagnosis.

An 18-year old female with mania developed confusion, trembling extremities, slurred speech, increased muscle tension, and hyperactive tendon reflexes 20 days after initiating treatment with routine dosages of lithium bicarbonate. When admitted to the hospital due to her acute neurological condition, her serum lithium concentration was in the therapeutic range (0.57 mmol/L). Most of her symptoms spontaneously reversed one week after stopping the lithium. Since its approval by the Food and Drug Administration in 1970 as treatment for bipolar disorders, several studies have addressed lithium-related neurotoxicity and the related risk factors; these studies all emphasize the relatively narrow therapeutic index of lithium. With the exception of intentional ingestion of large doses of lithium as an act of self-harm (resulting in ‘acute intoxication’ in untreated individuals or ‘acute-onchronic intoxication’ in currently treated individuals), toxicity during prolonged treatment with lithium (‘chronic intoxication’) usually results from progressive lithium accumulation due to renal dysfunction, underlying diseases, low sodium intake, and drug– drug interactions such as loop diuretics, angiotensinconverting enzyme inhibitors, or non-steroidal antiinflammatory drugs. [2]