How to manage mood instability in a patient on Latuda (lurasidone) 80mg and Depakote (valproate) 250mg bid with a platelet count of 391, considering potential risks of increasing Depakote dose?

Management of Mood Instability with Elevated Platelet Count on Depakote

You can safely increase the Depakote dose in this patient—a platelet count of 391,000/μL is well above any threshold of concern and does not contraindicate dose escalation. 1

Understanding the Platelet Count Context

Your patient's platelet count of 391,000/μL is elevated (thrombocytosis), not low. The clinical concern with valproate is thrombocytopenia (low platelets), not thrombocytosis. 2

• Valproate-induced thrombocytopenia typically occurs when platelet counts fall below 150,000/μL, with clinical significance at counts below 50,000/μL 1
• The risk of thrombocytopenia increases at valproate serum levels above 80 μg/mL, particularly in women and older patients 2
• Your patient's elevated platelet count of 391,000/μL poses no contraindication to increasing Depakote 1

Recommended Approach to Dose Escalation

Increase Depakote systematically while monitoring therapeutic levels and hematologic parameters:

• Increase from 250 mg BID (500 mg/day total) to 500 mg BID (1000 mg/day total) as the next step 1
• Target therapeutic valproate serum level: 40-90 μg/mL for mood stabilization 1
• The current dose of 500 mg/day is likely subtherapeutic for most patients with bipolar disorder 1

Essential Monitoring Parameters

Check the following at regular intervals during dose escalation:

• Valproate serum level to ensure therapeutic range (40-90 μg/mL) 1
• Complete blood count with platelets—monitor for thrombocytopenia (platelet count <150,000/μL), not thrombocytosis 1, 2
• Liver function tests (AST, ALT) to detect hepatotoxicity 1
• If platelet count falls below 50,000/μL, hold Depakote until recovery to >50,000/μL, then resume at reduced dose 1

Addressing the Underlying Mood Instability

Lurasidone (Latuda) 80 mg is within the therapeutic range but may need optimization:

• Lurasidone is FDA-approved for bipolar I depression at doses of 20-120 mg daily 3, 4, 5
• The therapeutic dose range is 40-160 mg daily, with your patient currently at 80 mg 3
• Lurasidone has demonstrated efficacy both as monotherapy and adjunctive to lithium or valproate for bipolar depression 4, 5, 6
• Consider increasing Latuda to 120 mg if depressive symptoms predominate, or optimize Depakote first if mood cycling is the primary issue 3, 4

Common Pitfalls to Avoid

• Do not confuse thrombocytosis with thrombocytopenia—elevated platelets do not require dose reduction or drug discontinuation 1, 2
• Do not assume current Depakote dose is therapeutic—250 mg BID is often subtherapeutic; always check serum levels 1
• Monitor for thrombocytopenia risk factors: female sex, age >50, and valproate levels >80 μg/mL increase risk 2
• Watch for hepatotoxicity: monitor liver enzymes regularly, especially during dose escalation 1
• Ensure Latuda is taken with food: lurasidone requires administration with at least 350 calories for adequate absorption 3

Specific Algorithm for This Patient

1. Increase Depakote to 500 mg BID (1000 mg/day total) 1
2. Check valproate level in 5-7 days after dose stabilization 1
3. Recheck CBC with platelets and liver enzymes in 1-2 weeks 1, 2
4. If mood instability persists after achieving therapeutic valproate level (40-90 μg/mL), consider increasing Latuda to 120 mg 3, 4
5. Continue monitoring CBC monthly during dose optimization, then every 3 months once stable 1, 2