Does Brivaracetam (BRV) cause mood disturbances as much as Levetiracetam (LEV)?

Brivaracetam Causes Significantly Fewer Mood Disturbances Than Levetiracetam

Brivaracetam (BRV) is associated with substantially lower rates of behavioral adverse events compared to levetiracetam (LEV), particularly regarding irritability, aggression, and mood disturbances, making it a preferred alternative when psychiatric side effects are a concern.

Comparative Incidence of Behavioral Adverse Events

The most comprehensive real-world evidence demonstrates clear differences in behavioral tolerability:

• Irritability occurs in 5.6% of patients on BRV versus 9.9% on LEV 1
• Aggression occurs in 2.5% of patients on BRV versus 2.6% on LEV 1
• Overall behavioral adverse events occur in 61.7% of patients on BRV versus 86.5% on LEV 2

The most striking difference appears in the behavioral category specifically, where LEV causes behavioral adverse events in 55.1% of patients compared to only 22.4% with BRV 2.

Discontinuation Rates Due to Behavioral Problems

Treatment discontinuation rates further highlight BRV's superior tolerability profile:

• Discontinuation for irritability: 0.8% with BRV versus 3.4% with LEV 1
• Discontinuation for aggression: 0.8% with BRV versus 2.4% with LEV 1
• Overall discontinuation for behavioral TEAEs: 47.1% with BRV versus 63.6% with LEV 2

Clinical Outcomes When Switching from LEV to BRV

For patients experiencing behavioral problems on LEV, switching to BRV provides substantial benefit:

• Between 33.3% to 83.0% of patients (weighted mean 66.6%) experience improvement in behavioral adverse events when switched from LEV to BRV 1
• Only 7.1% of patients develop new behavioral adverse events after switching from LEV to BRV 2
• Of patients who were non-responders to LEV, 46.2% still achieved positive seizure control with BRV 2

Mechanism and Clinical Implications

The behavioral tolerability advantage of BRV may relate to its pharmacological properties:

• BRV achieves 15-fold higher affinity for SV2A binding compared to LEV (IC50 of 0.46 μg/mL versus 4.02 μg/mL) 3
• BRV demonstrates faster brain penetration with displacement half-times of 18 minutes versus 28 minutes for LEV 3
• BRV achieves high synaptic vesicle occupancy more rapidly than LEV at therapeutic doses 3

Specific Psychiatric Manifestations with LEV

LEV carries well-documented psychiatric risks that are less prominent with BRV:

• LEV induces psychiatric side effects in 13.3% of adults, with 0.7% presenting severe symptoms including depression, agitation, or hostility 4
• Psychosis occurs in approximately 1.4% of LEV-treated patients 4
• Behavioral symptoms with LEV include agitation, anxiety, hostility, depression, and suicidality 5

Risk Factors for LEV-Induced Mood Changes

Certain patient characteristics predict poor tolerability of LEV:

• Morning chronotypes have significantly higher risk of LEV-induced mood changes, with 86.1% of intolerant patients being morning chronotypes 6
• Only 32% of morning chronotypes tolerate LEV, compared to 100% of evening chronotypes and 90.2% of intermediate chronotypes 6
• Patients with pre-existing psychiatric conditions (particularly schizoaffective disorder) are at elevated risk for severe behavioral reactions to LEV 4

Common Pitfalls and Clinical Caveats

When managing patients on these medications, consider:

• Behavioral adverse events with LEV can emerge beyond the initial titration period and may be the most common reason for drug discontinuation 4
• The FDA label for LEV (which applies to the drug class including BRV) notes that approximately half of behavioral events occur within the first 4 weeks 5
• In pediatric populations, LEV causes behavioral symptoms in 37.6% versus 18.6% with placebo, including hostility (11.9% vs 6.2%) and nervousness (9.9% vs 2.1%) 5
• Patients with prior positive response to LEV have a 78% likelihood of responding to BRV, but lack of LEV response does not preclude BRV efficacy 2