What happens when you take levetiracetam with vitamin b6?
Levetiracetam, sold most commonly as Keppra, is one of the most-prescribed anticonvulsants because it controls seizures well, has few drug interactions, and does not need blood-level monitoring. Its biggest practical drawback is behavioral: a significant minority of patients develop irritability, agitation, anxiety, depression, or aggression. Patient communities have nicknamed this "Keppra rage," and it is a leading reason people stop the drug. Adding pyridoxine (vitamin B6) appears to ease these behavioral effects in some people. Here is the chain of events as it is currently understood:
- You take levetiracetam for seizure control, and over days to weeks you notice new irritability, mood swings, or agitation.
- The active form of B6, pyridoxal-5-phosphate, is a required cofactor for making GABA, serotonin, and dopamine — the neurotransmitters that regulate mood and calm.
- The leading hypothesis is that levetiracetam subtly shifts the balance of these neurotransmitters, and supplying extra B6 helps the brain restore that balance.
- In practice, clinicians who add pyridoxine report that a portion of patients become noticeably less irritable, often within days to a few weeks, without losing seizure control.
Importantly, this is a possible benefit, not a dangerous interaction. B6 does not reduce how well levetiracetam works on seizures.
Why is this important?
This matters because the alternative to managing mood side effects is often abandoning a medication that is otherwise working well for seizures. A simple, low-cost adjunct that helps even some patients stay on an effective anticonvulsant is clinically valuable.
But the honest picture is that the evidence is mixed, not settled. Two randomized trials in children found that pyridoxine improved behavior compared with placebo. One randomized trial in adults did not show a clear benefit. Older case series report that roughly four or five in ten patients improve. The most likely reading is that a real subset benefits, the effect is not universal, and some of the improvement reflects the natural placebo response that comes with any subjective mood outcome.
It is also worth knowing that pyridoxine is not entirely benign. Taking high doses of B6 over a long period can cause a peripheral sensory neuropathy — numbness, tingling, and balance problems — which is partly reversible if caught early but can be lasting in severe cases. That is why this is a short-term, dose-conscious, supervised strategy rather than something to take indefinitely on your own. Finally, if behavioral changes are severe — especially suicidal thoughts, self-harm, or unmanageable aggression — the right move is to contact the prescriber promptly, not to reach for a supplement.
What should you do?
The first principle: if levetiracetam is working and you have no mood problems, you do not need B6. There is no evidence that taking it preventively stops side effects in people who never develop them.
Before any change: If you have noticed new irritability, mood changes, or agitation since starting or increasing levetiracetam, write down what you are seeing and when it started, and raise it with your prescriber. Ask whether a short, supervised trial of low-dose pyridoxine is reasonable for you. Do not pick a dose yourself — let your doctor or pharmacist set it, since the safe amount differs between adults and children.
Every day during a trial: Take levetiracetam exactly as prescribed, and take the pyridoxine dose your clinician agreed on, with food to reduce stomach upset. Keep a simple daily note on mood and irritability so you and your prescriber can judge whether it is helping.
After starting: Reassess with your prescriber within a few weeks. If mood has clearly improved, continue under supervision. If it has not, stop — pushing the dose higher is not the answer. If you develop numbness or tingling in your hands or feet at any point, stop the supplement and tell your doctor. And if behavioral side effects are severe, expect the conversation to be about reducing the levetiracetam dose or switching to another anticonvulsant rather than adding a vitamin.
Which specific products are affected?
On the medication side, this applies to all forms of levetiracetam, including:
- Keppra (immediate-release tablets and oral solution)
- Keppra XR (extended-release)
- Generic levetiracetam tablets and solutions
- Spritam (orally disintegrating tablets)
- Elepsia XR (extended-release)
On the supplement side, the relevant form is pyridoxine hydrochloride (vitamin B6), sold as standalone tablets and also included in B-complex supplements and multivitamins. Be aware that many "high-potency" B-complex products already contain far more B6 than the small amount the body needs each day, so it is easy to take more than you realize if you stack products.
The related supplement pyridoxal-5-phosphate (P5P) is the activated form, marketed as more bioavailable. There is no head-to-head evidence that P5P works better than plain pyridoxine for this specific purpose, but it is a reasonable alternative if regular B6 upsets your stomach. Whichever form you use, count it toward your total B6 intake when judging safety.
The science behind it
The evidence here is genuinely mixed, and it is fair to call it suggestive rather than definitive:
- Mahmoud AA, et al. (Pediatr Neurol. 2021;119:15-21; PMID 33823377) — a randomized, double-blind, placebo-controlled trial in children (n=105) that found pyridoxine improved levetiracetam-related behavioral side effects compared with placebo.
- Thananowan P, et al. (Epilepsy Behav. 2025; PMID 40913882) — a prospective, double-blind, randomized, placebo-controlled trial in children and adolescents that also supported a benefit of pyridoxine for neuropsychiatric side effects.
- Cheraghmakani H, et al. (Epilepsy Behav. 2022;135:108882; PMID 36228485) — a randomized, double-blind, placebo-controlled trial in adults (n=53) that did not show a clear benefit; the dose used was relatively low, which may partly explain the null result.
- Alsaadi T, et al. (Epilepsy Behav Case Rep. 2015; PMC4588452) — a case series in adults in which roughly four or five in ten patients showed improved behavioral symptoms after pyridoxine was added.
Taken together, the pediatric randomized data lean positive, the single adult randomized trial was null, and observational data suggest a meaningful but partial response. That is enough to justify a supervised trial in the right patient, but not enough to call it a reliable cure.
Frequently Asked Questions
Does vitamin B6 stop levetiracetam from controlling my seizures?
No. There is no evidence that pyridoxine reduces levetiracetam's anti-seizure effect. The interest in B6 is purely about easing mood and behavioral side effects.
Should I take B6 preventively when I start Keppra?
No. There is no evidence that taking B6 in advance prevents behavioral side effects in people who never develop them. It is only worth considering if mood problems actually appear.
How quickly would I know if it is working?
In the published reports, people who respond usually notice a difference within days to a few weeks. If there is no improvement after a few weeks at the dose your clinician set, it is unlikely to help.
Is vitamin B6 safe to take long-term?
Not at high doses. Taking large amounts of B6 over a long period can cause nerve damage with numbness and tingling. That is why this should be a short, supervised, dose-conscious trial — and why you should stop and call your doctor if you notice tingling in your hands or feet.
Can I just use a B-complex or multivitamin instead?
Possibly, but be careful: many high-potency B-complex products already contain a lot of B6, so combining them with a separate B6 tablet can push your intake higher than intended. Tell your doctor or pharmacist everything you take so the total can be checked.
What if my mood changes are severe?
Severe symptoms — especially suicidal thoughts, self-harm, or aggression you cannot control — are not something to manage with a supplement. Contact your prescriber promptly; the right step is usually a dose reduction or a switch to another anticonvulsant such as lamotrigine, brivaracetam, or lacosamide.
Key takeaways
- Adding vitamin B6 to levetiracetam is a possible way to ease the irritability and mood changes some people get on Keppra — it is a potential benefit, not a harmful interaction.
- The evidence is mixed: two pediatric randomized trials were positive, one adult randomized trial was null, and case series report a partial response.
- It is worth discussing with your prescriber only if mood side effects actually appear — there is no value in taking it preventively.
- Let your doctor or pharmacist set the dose, keep it short and supervised, and stop if you notice numbness or tingling.
- Severe behavioral changes call for a dose adjustment or a different antiepileptic, not a supplement.