A 65-year-old woman is brought to the emergency department by her son. The patient lives alone and works as a librarian. The son became concerned 2 days ago when "she didn't sound right and seemed somewhat confused over the phone." When he arrived at her home this morning, the patient was disoriented and her speech was slurred. Medical history is significant for diabetes mellitus controlled with metformin. The son says that a "mood disorder" runs in the family and that she has taken lithium, escitalopram, and risperidone for the past several years. A month ago, the patient was diagnosed with hypertension and arthritis, and treatment with chlorthalidone and acetaminophen was initiated. She does not use tobacco, alcohol, or illicit drugs. Temperature is 36.1 C (97 F) , blood pressure is 150/90 mm Hg, pulse is 52/min, and respirations are 16/min. Physical examination shows coarse hand tremor and an unstable gait. The patient is oriented to person but not to time or place. Item 1 of 2
Which of the following is the most likely cause of this patient's symptoms?

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Quizplus · Accepted Answer

Explanation: Lithium, a mood stabilizer used in bipolar disorder, has a narrow therapeutic index. This patient's gradual onset of neurologic symptoms (slurred speech, confusion, tremors, and ataxia) is consistent with lithium toxicity. Therapeutic lithium levels are 0.8-1.2 mEq/L. Serum lithium levels >1.5 mEq/L confirm toxicity, and levels >2.5 mEq/L require emergency management. Risks for lithium toxicity include low glomerular filtration rates (eg, the elderly, patients in renal failure), volume depletion, and drug interactions. This patient's lithium toxicity is most likely due to a drug interaction with chlorthalidone. Thiazide diuretics, such as chlorthalidone, increase sodium excretion in the distal tubule and cause slight volume depletion. The resulting increased proximal tubular reabsorption of sodium also promotes lithium reabsorption, leading to lithium toxicity. ACE inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs) also increase lithium levels. Patients who are co-administered these medications require close lithium level monitoring and lithium dosage reduction if necessary. (Choice A) NSAIDs, not acetaminophen, increase lithium levels and can result in lithium toxicity. (Choice C) Neuroleptic malignant syndrome is an acute, potentially fatal, idiosyncratic reaction to antipsychotic medications and is characterized by fever, extreme generalized rigidity, autonomic instability, and altered mental status. This patient is afebrile, has no rigidity, and has been on risperidone for several years. (Choice D) Serotonin syndrome can include confusion and tremulousness. However, it is typically caused by use of multiple serotonergic agents; myoclonus, hyperreflexia, hyperthermia, and tachycardia would also be expected. This patient's symptoms are more characteristic of lithium toxicity. (Choice E) This patient has several risk factors for stroke (eg, hypertension, diabetes). However, patients with stroke have an abrupt onset of focal neurologic deficits rather than the insidious onset of confusion, ataxia, and neuromuscular excitability seen in this patient. Educational objective: Lithium has a narrow therapeutic index, and serum levels >1.5 mEq/L confirm toxicity. Lithium toxicity (eg, confusion, ataxia, neuromuscular excitability) can be precipitated by volume depletion and drug interactions with thiazide diuretics, ACE inhibitors, and nonsteroidal anti-inflammatory drugs. References: Drug interactions with lithium: an update. (http://www.ncbi.nlm.nih.gov/pubmed/26936045) Antihypertensive therapy in patients on chronic lithium treatment for bipolar disorders. (http://www.ncbi.nlm.nih.gov/pubmed/26630207)

A 65-Year-Old Woman Is Brought to the Emergency Department by Her