A woman with bipolar I disorder maintained on lamotrigine conceives and continues the drug throughout pregnancy. What change in lamotrigine pharmacokinetics must be anticipated?
- A Hepatic glucuronidation is induced and plasma concentrations may fall by about half, requiring dose escalation ✓
- B Renal clearance falls, causing steady accumulation and dose reduction is required
- C Protein binding rises sharply, so free drug levels remain unchanged despite dose changes
- D Pharmacokinetics are essentially unchanged across all three trimesters
Correct answer: A. Hepatic glucuronidation is induced and plasma concentrations may fall by about half, requiring dose escalation
Explanation
Pregnancy induces uridine diphosphate glucuronosyltransferase, increasing lamotrigine clearance progressively, and trough concentrations can fall to around 25 to 35 percent of pre-pregnancy values by the third trimester, raising the risk of breakthrough seizures or relapse, so level-guided dose escalation is recommended. After delivery, clearance normalises rapidly, and failure to taper back causes toxicity with diplopia and ataxia.
Reference: Stahl's Essential Psychopharmacology, 5th ed.
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