What is the best approach for managing bipolar disorder in a patient with a history of Stevens-Johnson syndrome (SJS) with lamotrigine (Lamictal) and valproate (Depakote)?

Managing Bipolar Disorder in a Patient with History of Stevens-Johnson Syndrome from Lamotrigine

For patients with bipolar disorder and history of Stevens-Johnson syndrome (SJS) from lamotrigine, lithium should be considered the first-line treatment option due to its efficacy and lack of cross-reactivity with medications that caused prior SJS.

Understanding the Risk

Lamotrigine is one of the most common drugs associated with SJS/toxic epidermal necrolysis (TEN), as identified in the UK guidelines for management of SJS/TEN 1. The risk is particularly high:

• During initial weeks of treatment
• With rapid dose escalation
• When combined with valproate (which increases lamotrigine levels)

The FDA label for valproate specifically warns: "Serious skin reactions (such as Stevens-Johnson Syndrome and toxic epidermal necrolysis) have been reported with concomitant lamotrigine and valproate administration" 2.

Treatment Algorithm for Bipolar Disorder After SJS

First-Line Options:

1. Lithium monotherapy

   • Not associated with SJS
   • Established efficacy in bipolar disorder
   • Requires regular monitoring of levels and renal/thyroid function

2. Second-generation antipsychotics

   • Consider quetiapine, olanzapine, or aripiprazole
   • Lower risk of SJS than anticonvulsants
   • Monitor for metabolic side effects

Medications to Strictly Avoid:

• Lamotrigine (absolute contraindication)
• Valproate (high risk when combined with lamotrigine)
• Other high-risk anticonvulsants: carbamazepine, phenytoin, phenobarbital 1

Documentation and Safety Measures

Following SJS, the UK guidelines recommend 1:

• Document drug allergy prominently in patient's medical records
• Provide written information to patient about drugs to avoid
• Encourage patient to wear MedicAlert bracelet
• Report the episode to pharmacovigilance authorities
• Arrange follow-up with appropriate specialists

Monitoring and Management

• Regular psychiatric follow-up to assess mood stability
• Monitor for any skin reactions with new medications
• Consider dermatology consultation before starting any new psychotropic medication

Special Considerations

• Genetic testing may be beneficial as certain HLA genotypes (HLA-B15:02 in Southeast Asian populations, HLA-B31:01 in Japanese patients) increase susceptibility to lamotrigine-induced SJS 3
• Even with appropriate dosing and adjustments, SJS can still occur with lamotrigine 4
• Polytherapy increases the risk of adverse effects and should be avoided when possible 5

Pitfalls to Avoid

• Never reintroduce lamotrigine after SJS, even with slower titration
• Avoid combination therapy with multiple mood stabilizers if possible
• Don't assume that all anticonvulsants carry equal risk - some have higher association with SJS than others
• Don't overlook the importance of documenting the reaction in all medical records

By following these guidelines, clinicians can effectively manage bipolar disorder while minimizing the risk of recurrent severe cutaneous adverse reactions in patients with a history of SJS.