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Difficulty: MediumPsychopharmacology and Psychological Therapies

A 54-year-old woman is brought to the emergency department by her daughter due to progressive confusion, unsteadiness, and shaking. The patient has a history of bipolar I disorder that has been well controlled on a stable dose of lithium for the past 8 years. Two weeks ago, she visited a primary care clinic for routine evaluation and was started on a new daily medication. Today, her temperature is 37.1°C (98.8°F), blood pressure is 128/78 mm Hg, and heart rate is 82/min. Physical examination reveals an unsteady, broad-based gait and a coarse tremor in both hands. Deep tendon reflexes are 3+ bilaterally. She also reports several days of nausea, vomiting, and diarrhea. Which of the following medications was most likely added to her regimen two weeks ago?

  1. HydrochlorothiazideAnswer
  2. B
    Fluoxetine
  3. C
    Metoprolol
  4. D
    Haloperidol
  5. E
    Levothyroxine

Answer

Hydrochlorothiazide
The patient's presentation of confusion, ataxia, a coarse tremor, hyperreflexia, and gastrointestinal distress (nausea, vomiting, diarrhea) in the setting of chronic lithium therapy is highly characteristic of acute-on-chronic lithium toxicity. Lithium has a very narrow therapeutic index and is eliminated almost entirely by the kidneys. Thiazide diuretics (e.g., hydrochlorothiazide) inhibit the Na+/Cl- cotransporter in the distal convoluted tubule. This leads to mild volume depletion, which stimulates the kidneys to compensatorily increase sodium reabsorption in the proximal tubule. Because lithium is handled similarly to sodium in the proximal tubule, its reabsorption is concurrently increased, severely decreasing its clearance and precipitating toxicity. Other common drugs that increase lithium levels include NSAIDs, ACE inhibitors, and tetracyclines.

Step-by-Step Solution

1
Analyze the patient's clinical presentation and medication history.
The patient is on chronic lithium therapy and presents with acute neurologic (confusion, ataxia, coarse tremor, hyperreflexia) and gastrointestinal (nausea, vomiting, diarrhea) symptoms.
Identifying the clinical syndrome is necessary to determine the underlying pathophysiology.
2
Synthesize the findings to establish a diagnosis.
The combination of these specific neurologic and GI findings in a patient taking lithium is the classic presentation of acute-on-chronic lithium toxicity.
Lithium has a narrow therapeutic index and specific toxidrome characteristics.
3
Identify potential triggers for the toxicity based on the timeline.
A new medication was added two weeks ago. Medications that classically decrease lithium clearance include thiazide diuretics, NSAIDs, ACE inhibitors, and tetracyclines.
Lithium is almost exclusively excreted by the kidneys, and drugs affecting renal sodium handling alter its clearance.
4
Select the correct medication from the given options.
Hydrochlorothiazide is a thiazide diuretic that causes volume depletion, leading to increased proximal tubule reabsorption of both sodium and lithium, thereby precipitating toxicity.
This directly explains the patient's presentation following the addition of the new drug.

Key Concept

Lithium Toxicity and Drug Interactions
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Topics

Psychopharmacology and Psychological Therapies

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