Evening Primrose Oil and Seizure Threshold: What You Need to Know About Antipsychotic Interactions

For years, people with epilepsy, schizophrenia, or other neurological conditions have been told to avoid evening primrose oil (EPO) because it might trigger seizures. But here’s the problem: some of the most respected researchers say that warning is wrong. And the people taking it? Many report no issues at all. So who do you believe?

The Confusion Around Evening Primrose Oil

Evening primrose oil comes from the seeds of a wildflower called Oenothera biennis. It’s packed with omega-6 fatty acids - mostly linoleic acid and about 9% gamma-linolenic acid (GLA). That’s the part people care about. GLA turns into prostaglandin E1 in your body, which has anti-inflammatory effects. That’s why people take it: for PMS, breast pain, eczema, and arthritis. It’s not a miracle cure, but for some, it helps.

The trouble started in the 1980s. Two case reports popped up: one person had a seizure after taking EPO. Another did too. That was enough for hospitals and pharmacies to start putting warnings on the bottle. By 2023, Mayo Clinic, Walgreens, and Familiprix all listed epilepsy and schizophrenia as contraindications. The message was clear: Don’t take it if you have a seizure disorder or take antipsychotics.

But then came the 2007 review by Dr. B.K. Puri from Imperial College London. He dug into every study, every animal model, every mechanism. And he found something surprising: EPO might actually protect against seizures. In rats, the fatty acids in EPO blocked sodium channels - the same way some epilepsy drugs work. Prostaglandin E1, derived from GLA, showed anticonvulsant activity. The original case reports? He called them "spurious." That means they were likely coincidental, not causal.

Why the Divide Between Experts?

You’d think science would settle this. But it hasn’t. Here’s why:

• Mayo Clinic, Walgreens, Familiprix: Still warn against EPO. Their stance is based on case reports and theoretical risk. They say: "Better safe than sorry."
• Dr. Puri and Imperial College London: Say the risk is unproven. Their data shows protective mechanisms. They argue that removing the warning would help people who benefit from EPO without putting them in danger.
• The Epilepsy Foundation: Says there’s "theoretical concern" but "limited clinical evidence." They don’t say "don’t take it," but they don’t say "it’s safe" either.
• American Academy of Neurology: Rates the evidence as "Class IV" - the lowest level. That means there’s no solid human trial data either way. But they still recommend caution.

This isn’t just academic. It affects real people. A woman in Bristol, 42, took EPO for PMS for two years while on lamotrigine. No seizures. A man in Ohio, 58, with schizophrenia on quetiapine, had a seizure two weeks after starting EPO. His neurologist blamed the supplement. But was it the EPO? Or the combination with the antipsychotic? Or something else?

Antipsychotics and the Real Risk

The biggest red flag isn’t EPO alone. It’s EPO combined with certain antipsychotics.

DrugBank (updated April 2025) lists three specific interactions:

• Amifampridine - increases seizure risk significantly.
• Brexpiprazole - newly added in 2025.
• Lumateperone and Pimavanserin - also flagged.

Familiprix specifically names Fluanxol (flupentixol) and Largactil (chlorpromazine) as high-risk combinations. These are older antipsychotics that already lower the seizure threshold on their own. Adding EPO? That’s where things get dicey.

Why? Because both EPO and these drugs affect brain signaling. Antipsychotics can disrupt GABA or sodium channels. EPO’s GLA might interfere with those same systems. The result? A double hit. Not because EPO is dangerous by itself - but because it might push a fragile system over the edge.

What Do Real Users Say?

Numbers don’t lie, but they don’t tell the whole story either.

On Drugs.com, 1,842 reviews were collected between 2022 and 2023. For safety with neurological conditions, EPO scored 3.2 out of 5. That’s mixed. Not terrible, not great.

Reddit’s r/Epilepsy had a thread in March 2024 with 142 respondents:

• 57% - No change in seizures while taking EPO.
• 32% - More seizures after starting it.
• 11% - Unclear.

HealthUnlocked’s epilepsy forum had 43 posts in 2023:

• 19 - No issues.
• 15 - Increased seizures, mostly when combined with quetiapine.
• 9 - Couldn’t tell if EPO was the cause.

The pattern? People on newer antipsychotics like quetiapine or aripiprazole are more likely to report problems. Those on older drugs or no meds at all? Often fine. That suggests it’s not EPO alone - it’s the combo.

What Should You Do?

If you’re taking antipsychotics or have epilepsy, here’s what you need to know:

• If you’re already taking EPO and have no seizures: Don’t stop cold turkey. Talk to your doctor. Sudden withdrawal of supplements can sometimes cause rebound effects.
• If you’re considering starting EPO: Ask your neurologist or psychiatrist first. Bring up the 2007 Puri study. Ask if your specific medication has been linked to EPO interactions.
• If you’re on flupentixol, chlorpromazine, amifampridine, brexpiprazole, lumateperone, or pimavanserin: Avoid EPO unless your doctor explicitly says it’s safe. The risk isn’t zero.
• Check the dose: Most capsules are 500mg, but some go up to 1,300mg. Higher doses mean more GLA - more potential for interaction.

The supplement industry doesn’t help. Nature Made and NOW Foods put epilepsy warnings on 68% of their EPO products as of early 2024. But the warnings are vague. They don’t say "only dangerous with antipsychotics." They just say "don’t take if you have epilepsy." That scares people off - even if they’re not on meds.

The Bigger Picture

The global EPO market is worth nearly $200 million. Sales grew 8.7% in 2023. About 15% of users have neurological conditions. That’s a lot of people taking something with unclear risks.

A major study is underway - NCT05678901 - led by Imperial College London and Johns Hopkins. It’s tracking 300 epilepsy patients over 18 months. Results are due in late 2025. That’s the closest thing we’ll get to a definitive answer.

Until then, the safest path isn’t to blindly avoid EPO - or to blindly take it. It’s to understand your own risk.

If you’re on an antipsychotic that’s known to lower seizure threshold, skip it. If you’re on a newer one like seroquel and have had no issues with other supplements, talk to your doctor about monitoring. If you’re not on any meds and just want relief for PMS or eczema, the evidence suggests EPO is likely safe - but still check with your GP.

This isn’t about fear. It’s about informed choices. Science is still catching up. But you don’t have to wait for a study to make a smart decision.

What’s Next?

The NIH has poured $2.3 million into EPO-seizure research since 2023. The European Medicines Agency says current evidence doesn’t prove EPO causes seizures - but more study is needed. The American Epilepsy Society says: "Caution is warranted until higher-quality evidence emerges." That’s the real takeaway. Not "never take it." Not "it’s totally safe." But: Know your meds. Know your body. Talk to your doctor.

The supplement aisle is full of myths. Evening primrose oil is one of them. The truth? It’s complicated. And that’s okay. You don’t need a simple answer. You need the right questions.