What alternative mood‑stabilising or atypical antipsychotic medication can I prescribe for a patient with bipolar II disorder who developed an itchy rash with bumps on the legs after increasing lamotrigine from 100 mg to 150 mg?

Discontinue Lamotrigine Immediately and Consider Alternative Mood Stabilizers

The development of an itchy rash with bumps after increasing lamotrigine from 100 mg to 150 mg requires immediate discontinuation of the medication, as this may represent a hypersensitivity reaction that could progress to Stevens-Johnson syndrome or other serious dermatologic complications. 1, 2

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Immediate Management of the Rash

Discontinuation Protocol

• Stop lamotrigine immediately without tapering, as the risk of serious rash (including Stevens-Johnson syndrome) outweighs concerns about abrupt discontinuation when hypersensitivity is suspected 2, 3
• The incidence of serious rash with lamotrigine is approximately 0.1%, and one case of Stevens-Johnson syndrome has been documented in bipolar disorder trials 3
• Do not rechallenge with lamotrigine after a rash develops, as reintroduction dramatically increases the risk of severe hypersensitivity reactions 1

Symptomatic Treatment of Pruritus

• Apply topical corticosteroid (mometasone furoate 0.1% ointment or betamethasone valerate 0.1% ointment) to affected areas 4
• Consider oral antihistamines: loratadine 10 mg daily for daytime (non-sedating) or diphenhydramine 25-50 mg at bedtime for nocturnal pruritus 4
• If pruritus persists despite antihistamines, consider gabapentin 900-3600 mg daily or pregabalin 25-150 mg daily as second-line agents 4

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Alternative Mood Stabilizers for Bipolar II Disorder

First-Line Alternatives

Lithium is the preferred first-line alternative, as it is the only FDA-approved mood stabilizer for bipolar disorder in patients age 12 and older, with superior evidence for long-term efficacy in maintenance therapy and unique anti-suicidal effects (reducing suicide attempts 8.6-fold and completed suicides 9-fold) 1

Lithium Initiation Protocol

• Baseline laboratory assessment: complete blood count, thyroid function tests (TSH, free T4), urinalysis, BUN, creatinine, serum calcium, and pregnancy test in females 1
• Starting dose: 300 mg twice to three times daily, titrated to achieve serum levels of 0.8-1.2 mEq/L for acute treatment or 0.6-1.0 mEq/L for maintenance 1
• Monitoring schedule: Check lithium level after 5 days at steady-state dosing, then every 3-6 months along with renal and thyroid function 1

Important Lithium Considerations

• Lithium requires adequate hydration and consistent salt intake to maintain stable levels 1
• Common side effects include fine tremor, nausea, polyuria, and weight gain 1
• Lithium has no significant sedation, making it superior to valproate when sedation is a concern 1

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Second-Line Alternative: Valproate (Divalproex)

Valproate is particularly effective for irritability, mixed features, and rapid cycling, which are common in bipolar II disorder 1

Valproate Initiation Protocol

• Baseline laboratory assessment: liver function tests, complete blood count with platelets, and pregnancy test in females 1
• Starting dose: 125 mg twice daily, titrated to therapeutic blood levels of 50-100 μg/mL 1
• Monitoring schedule: Check valproate level, liver function tests, and complete blood count at 1 month, then every 3-6 months 1

Important Valproate Considerations

• Valproate is associated with weight gain and sedation, which may be problematic for some patients 1
• Valproate carries risk of polycystic ovary syndrome in females, an additional concern beyond metabolic effects 1
• Valproate should not be used in pregnancy due to teratogenic risk 1

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Third-Line Alternative: Atypical Antipsychotics

Quetiapine or aripiprazole can be considered as monotherapy or adjunctive therapy for bipolar II disorder, particularly when depressive symptoms predominate 1

Quetiapine

• Dosing: Start 25-50 mg at bedtime, titrate to 300-600 mg daily in divided doses 1
• Advantages: Effective for both depressive and hypomanic symptoms; sedating properties may help with insomnia 1
• Disadvantages: Significant metabolic risk including weight gain, diabetes, and dyslipidemia; requires intensive metabolic monitoring 1

Aripiprazole

• Dosing: Start 5 mg daily, titrate to 10-15 mg daily 1
• Advantages: Favorable metabolic profile compared to other atypical antipsychotics; low sedation risk 1
• Disadvantages: May cause akathisia; less effective for depressive symptoms compared to quetiapine 1

Metabolic Monitoring for Atypical Antipsychotics

• Baseline: BMI, waist circumference, blood pressure, fasting glucose, fasting lipid panel 1
• Follow-up: BMI monthly for 3 months then quarterly; blood pressure, fasting glucose, and lipids at 3 months then annually 1

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Combination Therapy Considerations

If monotherapy with lithium or valproate proves insufficient after a 6-8 week trial at therapeutic doses, consider adding an atypical antipsychotic (aripiprazole or quetiapine) for treatment-resistant cases 1

• Combination therapy with lithium or valproate plus an atypical antipsychotic is superior to monotherapy for severe presentations and provides better relapse prevention 1
• Maintain combination therapy for at least 12-24 months after achieving mood stabilization 1

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Psychosocial Interventions (Essential Adjunct)

Pharmacotherapy alone is insufficient; psychosocial interventions should accompany all medication treatment 1

• Psychoeducation: Provide information about symptoms, course of illness, treatment options, and critical importance of medication adherence 1
• Cognitive-behavioral therapy (CBT): Strong evidence for addressing both depressive and anxiety components of bipolar disorder 1
• Family-focused therapy: Helps with medication supervision, early warning sign identification, and enhanced problem-solving skills 1

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Common Pitfalls to Avoid

• Never rechallenge with lamotrigine after a rash develops, as this dramatically increases the risk of Stevens-Johnson syndrome 1, 2
• Avoid antidepressant monotherapy in bipolar II disorder, as this can trigger hypomanic episodes, rapid cycling, and mood destabilization 1
• Do not prematurely discontinue maintenance therapy; withdrawal of mood stabilizers is associated with relapse rates exceeding 90% in noncompliant patients versus 37.5% in compliant patients 1
• Ensure adequate trial duration (6-8 weeks at therapeutic doses) before concluding a medication is ineffective 1
• Monitor for metabolic side effects when using atypical antipsychotics, particularly weight gain, which occurs in approximately 16% of patients 1

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Expected Timeline for Response

• Lithium or valproate: Therapeutic effects become apparent after 1-2 weeks, with full response by 4-6 weeks at therapeutic levels 1
• Atypical antipsychotics: Initial response within 1-2 weeks, with maximal benefit by 4-6 weeks 1
• Maintenance therapy: Continue for minimum 12-24 months after stabilization; some patients require lifelong treatment 1