There is no established evidence that adding Vitamin B12 to levetiracetam (Keppra) improves behavioral side effects.
The question appears to conflate Vitamin B12 with Vitamin B6 (pyridoxine), which has been studied for levetiracetam-induced behavioral problems. If you are asking about Vitamin B6 (pyridoxine), there is preliminary evidence suggesting modest benefit, but if you are specifically asking about Vitamin B12, there is no evidence supporting this practice.
The Evidence on Pyridoxine (Vitamin B6) - Not B12
One randomized controlled trial examined pyridoxine (B6) for levetiracetam-induced behavioral symptoms in pediatric patients 1. This study found:
- Both pyridoxine and placebo groups showed significant reduction in behavioral symptoms at 2,4, and 6 weeks
- The pyridoxine group demonstrated almost double the relative reduction compared to placebo (1.9x at 2 weeks, 2.0x at 4 weeks, 1.8x at 6 weeks, P=0.001)
- However, the study had significant limitations preventing conclusive recommendations
The evidence for pyridoxine remains insufficient to make a firm recommendation, and no such evidence exists for Vitamin B12.
What We Know About Levetiracetam Behavioral Side Effects
The FDA label clearly documents that levetiracetam causes significant behavioral problems 2:
- Adults: 13.3% experience behavioral symptoms (aggression, agitation, anger, anxiety, depression, irritability) versus 6.2% on placebo
- Pediatric patients: 37.6% experience behavioral symptoms versus 18.6% on placebo
- Hostility occurs in 11.9% of pediatric patients versus 6.2% on placebo
- These events typically occur within the first 4 weeks of treatment
Clinical Approach to Levetiracetam Behavioral Side Effects
When behavioral problems emerge on levetiracetam:
- First-line: Consider dose reduction (0.8% of patients in trials required this) 2
- Second-line: Switch to an alternative anti-seizure medication if symptoms persist
- Do not routinely add Vitamin B12 - there is no evidence for this practice
Vitamin B12 Deficiency Context
Vitamin B12 deficiency itself can cause neuropsychiatric symptoms including cognitive difficulties, mood changes, and behavioral problems 3, 4. However:
- Testing for B12 deficiency should only occur when specific risk factors or symptoms of deficiency are present 3
- There is no high-quality evidence supporting routine B12 supplementation for psychiatric disorders 4
- B12 supplementation is only indicated for confirmed B12 deficiency 5, 6
Critical Pitfall to Avoid
Do not confuse Vitamin B6 (pyridoxine) with Vitamin B12 (cobalamin). These are entirely different vitamins with different mechanisms and indications. The limited preliminary data on behavioral side effects from levetiracetam involves B6, not B12.