What is the best next step in managing a patient with depressive symptoms on Lithium (lithium) 1200 mg daily and Risperidone (risperidone) with a lithium level of 0.9 and normal renal function, as indicated by a Blood Urea Nitrogen (BUN) of 8?

Management of Depressive Symptoms in a Patient on Lithium and Risperidone

Adding lamotrigine (Lamictal) is an appropriate next step for managing persistent depressive symptoms in a patient on lithium with adequate serum levels and normal renal function. 1

Current Clinical Situation Assessment

• Patient is on Lithium 1200 mg daily (serum level 0.9 mmol/L) and Risperidone
• BUN is 8, indicating normal renal function
• Patient reports persistent depressive symptoms despite therapeutic lithium levels

Rationale for Adding Lamotrigine

Lamotrigine is a reasonable choice for several reasons:

1. Evidence for augmentation therapy: When patients with bipolar disorder have persistent depressive symptoms despite adequate lithium levels, augmentation with another mood stabilizer is indicated 1

2. Specific support for lamotrigine: The INTEGRATE guidelines specifically mention lamotrigine as a consideration for prophylactic treatment when using high clozapine concentrations, suggesting its utility in managing mood disorders with complex presentations 1

3. Safety with lithium: Lamotrigine can be safely combined with lithium, and this combination may provide better mood stabilization than either agent alone 1

4. Targeting depressive symptoms: Lamotrigine has particular efficacy for the depressive phase of bipolar disorder, with evidence supporting its use for bipolar depression 1

Implementation Plan

1. Starting dose and titration:

   • Begin with 25 mg daily for 2 weeks
   • Increase to 50 mg daily for 2 weeks
   • Then increase by 50 mg every 1-2 weeks
   • Target dose: 100-200 mg daily (based on response and tolerability)

2. Monitoring parameters:

   • Continue monitoring lithium levels every 3-6 months
   • Watch for skin rash (particularly in first 8 weeks), which can be a serious adverse effect of lamotrigine
   • Assess improvement in depressive symptoms at 4-6 weeks after reaching therapeutic dose

Alternative Options to Consider

If lamotrigine is contraindicated or ineffective, consider:

1. Antidepressant augmentation: Adding an antidepressant (preferably an SSRI) to lithium and risperidone may be beneficial, though there is risk of mood destabilization 2

2. Optimizing lithium dosage: While the current level of 0.9 mmol/L is therapeutic, some patients may benefit from levels at the higher end of the therapeutic range (0.8-1.0 mmol/L) 3

3. Switch risperidone to another antipsychotic: Quetiapine has better evidence for bipolar depression than risperidone 1

Important Considerations and Potential Pitfalls

• Rash monitoring: The most serious concern with lamotrigine is the risk of Stevens-Johnson syndrome. Slow titration is essential to minimize this risk.

• Drug interactions: Lamotrigine levels may be affected by other medications, but the interaction with lithium is minimal.

• Avoid antidepressant monotherapy: Adding an antidepressant without a mood stabilizer can potentially trigger mania in bipolar patients 1

• Lithium toxicity risk: Even at therapeutic levels, lithium can cause neurotoxicity, especially when combined with other psychotropic medications 4. Regular monitoring is essential.

• Compliance considerations: Single daily dosing of lithium may improve compliance compared to multiple daily doses, without significant differences in efficacy or side effect profile 5

By adding lamotrigine to the current regimen of lithium and risperidone, you can effectively target the persistent depressive symptoms while maintaining mood stability in this patient.