Can a patient take Depakote (valproate) and lithium at the same time?

Concurrent Use of Depakote (Valproate) and Lithium

Yes, patients can take Depakote (valproate) and lithium concurrently, and this combination is often used in bipolar disorder treatment, particularly for patients who have inadequate response to monotherapy. 1

Safety and Pharmacokinetic Considerations

• The combination of lithium and valproate appears to be pharmacokinetically safe, with minimal interaction between the two medications:
  • Lithium pharmacokinetics remain largely unchanged when valproate is added 2
  • Valproate levels may rise slightly during lithium co-administration, but this is generally not clinically significant 2
  • The FDA label for valproate specifically states: "Co-administration of valproate (500 mg BID) and lithium carbonate (300 mg TID) to normal male volunteers had no effect on the steady-state kinetics of lithium" 3

Clinical Applications

• This combination is particularly useful for:
  • Bipolar disorder refractory to monotherapy 4, 5
  • Bipolar depression (lithium + valproate is considered a first-line combination therapy) 1
  • Patients with mixed episodes or rapid cycling

Monitoring Requirements

When using this combination, regular monitoring should include:

• Serum levels of both medications
• Thyroid function tests
• Renal function tests
• Liver function tests
• Complete blood count
• Weight and BMI
• Blood pressure
• Fasting glucose and lipid panel 1

Potential Concerns

While generally safe, clinicians should be aware of:

1. Neurological effects: Both medications can affect the central nervous system, so monitoring for excessive sedation or cognitive effects is important 6

2. Thyroid function: Lithium can affect thyroid function, requiring regular monitoring

3. Renal function: Lithium requires careful monitoring of kidney function

4. Teratogenicity: Both medications carry risks during pregnancy

Clinical Evidence Supporting Combination Use

• Case reports have shown dramatic responses to the combination of lithium and valproate in patients who failed to respond to either drug as monotherapy 4

• In a prospective clinical trial of refractory bipolar disorder, 33% of patients had moderate to marked responses to valproate plus lithium; notably, some of these patients had not responded to any previous treatment 5

• The combination of valproate and lithium appears to be better tolerated than some other combination therapies 7

Important Cautions

• Avoid adding benzodiazepines to this combination due to risk of oversedation 1

• If discontinuation is necessary, the American Academy of Child and Adolescent Psychiatry suggests removing adjunctive agents first before considering lithium or valproate reduction 1

• Lithium should be temporarily discontinued during serious intercurrent illness that increases the risk of acute kidney injury 1

This combination represents an important treatment option for patients with bipolar disorder who do not achieve adequate symptom control with monotherapy, with evidence supporting both its safety and efficacy when properly monitored.