What mood stabilizer can be used with Keppra (levetiracetam)?

Mood Stabilizer Selection with Concurrent Keppra (Levetiracetam) Use

Lamotrigine is the preferred mood stabilizer when a patient is using Keppra (levetiracetam), as it provides effective mood stabilization without significant drug interactions and has complementary mechanisms of action. 1, 2

Primary Recommendation: Lamotrigine

Lamotrigine functions as a "depression mood stabilizer" that stabilizes mood from below baseline without inducing manic switch or episode acceleration, making it particularly valuable for bipolar depression. 2

Key Advantages of Lamotrigine with Keppra:

• Lamotrigine significantly delays time to intervention for any mood episode in bipolar I disorder maintenance therapy, with strong evidence from controlled trials 1
• No significant pharmacokinetic interactions exist between lamotrigine and levetiracetam, allowing safe co-administration 3
• Lamotrigine is associated with low risk for depression (<1%) and appears to have positive effects on mood 4
• The combination addresses both seizure control (if needed) and mood stabilization without compounding adverse effects 5

Critical Titration Requirements:

Lamotrigine must be titrated slowly to minimize the risk of Stevens-Johnson syndrome and serious rash. 1

• Start with standard titration schedule and never load rapidly 1
• If lamotrigine was discontinued for more than 5 days, restart with the full titration schedule rather than resuming the previous dose 1

Alternative Options When Lamotrigine is Contraindicated

Lithium as Second-Line Choice:

• Lithium reduces suicide attempts 8.6-fold and completed suicides 9-fold, an effect independent of its mood-stabilizing properties 1
• Target serum level of 0.8-1.2 mEq/L for acute treatment 1
• No significant drug interactions with levetiracetam 6
• Requires monitoring of lithium levels, renal and thyroid function, and urinalysis every 3-6 months 1

Valproate (Divalproex) as Third-Line:

• Generally better tolerated than other mood stabilizers with therapeutic blood level of 40-90 mcg/mL 6
• Monitor liver enzyme levels, platelets, prothrombin time, and partial thromboplastin time as indicated 6
• Particularly effective for mixed or dysphoric mania 1
• No significant interactions with levetiracetam reported 5

Mood Stabilizers to AVOID with Keppra

Carbamazepine - NOT Recommended:

• Carbamazepine has problematic side effects and requires monitoring of complete blood cell count and liver enzyme levels regularly 6
• Multiple potential drug interactions complicate polypharmacy regimens 4

Critical Clinical Considerations

Levetiracetam's Psychiatric Profile:

Levetiracetam itself carries an intermediate risk for mood disorders, with depression occurring in approximately 4% or lower of patients, but can cause severe behavioral adverse effects including rage and suicidality in susceptible individuals. 4, 7

• Levetiracetam-induced rage is characterized by seething rage, uncontrollable anger, fits of fury, depression, violence, and suicidal tendencies 7
• This occurs more frequently in patients with prior mood or psychotic disturbances 7
• Neuropsychiatric evaluation for prior mood or psychiatric disorders is essential before initiating levetiracetam therapy 7

Monitoring Algorithm:

• Baseline assessment should include complete psychiatric history, particularly prior mood disorders or psychotic symptoms 7
• Monitor for early features of levetiracetam-induced behavioral changes by both caregivers and physicians 7
• If mood destabilization occurs after adding a mood stabilizer, consider whether levetiracetam itself is contributing to psychiatric symptoms 7

Treatment Duration:

• Maintenance therapy with the chosen mood stabilizer should continue for at least 12-24 months after the acute episode 1
• Some individuals may require lifelong treatment when benefits outweigh risks 1
• Withdrawal of maintenance therapy, especially lithium, dramatically increases relapse risk within 6 months 1

Common Pitfalls to Avoid

• Never use antidepressant monotherapy in bipolar disorder due to risk of mood destabilization, mania induction, and rapid cycling 1
• Avoid rapid titration of lamotrigine, which increases risk of serious rash including Stevens-Johnson syndrome 1
• Do not overlook levetiracetam as a potential contributor to mood symptoms, particularly rage and depression 4, 7
• Inadequate duration of maintenance therapy leads to relapse rates exceeding 90% in noncompliant patients 1