A 29-year-old woman with bipolar II disorder is being started on lamotrigine. Which serious adverse effect requires a mandatory slow titration protocol (dose escalation over 6 weeks), and which concurrent drug most dangerously accelerates this risk?
- A Stevens-Johnson syndrome / toxic epidermal necrolysis; valproate ✓
- B Hepatotoxicity; carbamazepine
- C Aplastic anaemia; clonazepam
- D Serotonin syndrome; fluoxetine
Explanation
Lamotrigine's most feared adverse effect is serious cutaneous reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Valproate inhibits UGT enzymes that metabolise lamotrigine, roughly doubling its plasma levels; this dramatically increases the risk of SJS/TEN, hence the starting dose of lamotrigine must be halved and titration slowed to every 2 weeks when co-prescribed with valproate. Rapid dose escalation regardless of co-medication is the main modifiable risk factor. Carbamazepine induces lamotrigine metabolism, reducing rather than increasing levels.
Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.
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