A 28-year-old man with bipolar I disorder in remission is on lithium maintenance therapy. He develops a severe upper respiratory tract infection with fever and is advised to take ibuprofen for pain and fever. Which of the following is the most appropriate action regarding his lithium therapy?

Explanation

## Lithium–NSAID Interaction: Clinical Management **Key Point:** NSAIDs inhibit renal prostaglandin synthesis, reducing glomerular filtration and lithium clearance. This can precipitate lithium toxicity even at therapeutic doses. Acetaminophen is the preferred analgesic in patients on lithium. ## Mechanism of Interaction 1. NSAIDs block COX-1 and COX-2 enzymes 2. ↓ Renal prostaglandin E₂ production 3. ↓ Glomerular filtration rate (GFR) 4. ↓ Lithium clearance → ↑ serum lithium levels 5. Risk of toxicity (tremor, confusion, polyuria, cardiac arrhythmias) **High-Yield:** Lithium has a narrow therapeutic index (0.6–1.2 mEq/L). Even a 20–30% increase in serum levels can cause toxicity. NSAIDs can increase lithium levels by 20–40% within days. ## Safe Analgesic Alternatives in Lithium-Treated Patients | Drug | Status | Notes | |------|--------|-------| | **Acetaminophen** | ✓ Safe | First-line analgesic/antipyretic; no interaction | | **NSAIDs** | ✗ Avoid | ↑ Lithium levels by 20–40%; risk of toxicity | | **Aspirin (low-dose)** | ⚠ Caution | Minimal effect on lithium clearance; acceptable if necessary | | **Selective COX-2 inhibitors** | ✗ Avoid | Same risk as non-selective NSAIDs | | **Opioids** | ✓ Safe | Use if acetaminophen insufficient; no interaction | **Clinical Pearl:** If an NSAID is absolutely necessary (e.g., severe arthritis), reduce lithium dose by 25–50%, increase fluid intake, and check serum lithium levels 3–5 days after starting the NSAID. Recheck levels after stopping the NSAID, as levels will rise again. ## Management Strategy for This Patient 1. **Avoid NSAIDs** — counsel on acetaminophen as first-line 2. **Maintain hydration** — increased fluid intake reduces lithium toxicity risk 3. **Monitor serum lithium levels** — check 3–5 days after any medication change 4. **Educate the patient** — provide written list of unsafe drugs (NSAIDs, ACE inhibitors, thiazides, dehydration) **Warning:** Other drugs that ↑ lithium levels: ACE inhibitors, angiotensin II receptor blockers, thiazide diuretics, loop diuretics (with caution), and trimethoprim. Dehydration (vomiting, diarrhea, excessive sweating) also increases lithium toxicity risk.