What are the next steps for an adult patient with a history of bipolar disorder, who recently transitioned from lithium to lamictal (lamotrigine), and is now experiencing itchiness and erythematous symptoms?

Immediate Discontinuation of Lamotrigine Required

Stop lamotrigine immediately and do not restart—itchiness and erythematous symptoms during the transition from lithium to lamotrigine represent a potentially life-threatening drug reaction that can progress to Stevens-Johnson syndrome or toxic epidermal necrolysis. 1

Critical Safety Assessment

Any rash or skin reaction with lamotrigine is a medical emergency until proven otherwise. The FDA label explicitly warns that serious skin rashes requiring hospitalization and discontinuation of treatment occur in approximately 0.1% of patients, with one documented case of Stevens-Johnson syndrome in bipolar disorder trials 1. The risk is highest within the first 2-8 weeks of treatment 1.

Immediate Actions Required

• Discontinue lamotrigine immediately—do not wait for the rash to worsen, as there is no way to predict if a mild rash will progress to a serious, potentially fatal reaction 1
• Examine the patient urgently to assess for signs of serious hypersensitivity: blistering, peeling skin, painful oral sores, mucosal involvement, fever, lymphadenopathy, or systemic symptoms 1
• Do not rechallenge with lamotrigine even if the rash resolves—reintroduction after a rash carries unacceptable risk of severe reaction 1

Signs That Indicate Severe Reaction (Require Emergency Department Evaluation)

• Blistering or peeling of skin 1
• Painful sores in mouth or around eyes 1
• Fever, swollen lymph glands, or facial swelling 1
• Systemic symptoms: severe muscle pain, unusual bruising/bleeding, yellowing of skin/eyes 1

Alternative Mood Stabilization Strategy

Restart lithium or initiate valproate as the primary mood stabilizer, as both are first-line agents for bipolar disorder without the serious rash risk of lamotrigine. 2

If Lithium Was Previously Effective

• Resume lithium at the previous therapeutic dose if it was discontinued recently (within 5 days), or restart with full titration if discontinued longer 2
• Target lithium level of 0.8-1.2 mEq/L for acute treatment 2
• Obtain baseline labs: complete blood count, thyroid function, urinalysis, BUN, creatinine, serum calcium 2
• Monitor lithium levels, renal and thyroid function every 3-6 months 2

If Lithium Was Ineffective or Not Tolerated

• Initiate valproate starting at 125 mg twice daily, titrating to therapeutic blood level of 50-100 μg/mL 2, 3
• Obtain baseline liver function tests, complete blood count, and pregnancy test in females 3
• Monitor serum drug levels, hepatic function, and hematological indices every 3-6 months 3
• Valproate is particularly effective for mixed episodes and irritability 2

Combination Therapy for Severe or Treatment-Resistant Cases

• Add an atypical antipsychotic (aripiprazole 5-15 mg/day, risperidone 2 mg/day, or quetiapine 400-800 mg/day) to lithium or valproate if mood symptoms are severe 2, 4
• Combination therapy with mood stabilizer plus atypical antipsychotic is superior to monotherapy for acute symptom control and relapse prevention 2
• Aripiprazole has the most favorable metabolic profile among atypical antipsychotics 2

Why Lamotrigine Cannot Be Restarted

The FDA label explicitly states that if lamotrigine is discontinued for more than 5 days, the full titration schedule must be restarted rather than resuming the previous dose to minimize rash risk. 5 However, any patient who develops a rash on lamotrigine should never be rechallenged due to the risk of severe hypersensitivity reaction 1.

Lamotrigine-Specific Risk Factors Present in This Case

• Recent initiation (highest risk period is first 2-8 weeks) 1
• Transition from another medication may have involved rapid titration 1
• Any rash during lamotrigine treatment is a contraindication to continued use 1

Long-Term Maintenance Planning

Continue the alternative mood stabilizer (lithium or valproate) for at least 12-24 months after achieving mood stability, with some patients requiring lifelong treatment 2, 3. Withdrawal of maintenance therapy dramatically increases relapse risk, with over 90% of noncompliant patients relapsing versus 37.5% of compliant patients 2.

Psychosocial Interventions to Accompany Pharmacotherapy

• Provide psychoeducation about bipolar disorder symptoms, course, treatment options, and critical importance of medication adherence 2
• Implement cognitive-behavioral therapy, which has strong evidence for both depressive and anxiety components of bipolar disorder 2
• Engage family members in treatment to improve medication supervision and early warning sign identification 2

Common Pitfalls to Avoid

• Never continue lamotrigine "to see if the rash gets worse"—serious reactions can develop rapidly and unpredictably 1
• Never attempt slow dose reduction of lamotrigine in the presence of rash—immediate discontinuation is mandatory 1
• Never rechallenge with lamotrigine after any rash, even if it appeared mild and resolved quickly 1
• Do not delay alternative mood stabilizer initiation while waiting for rash resolution—mood destabilization can occur during the medication gap 2