Tramadol and Seizure Disorders: What You Need to Know About the Risk

Tramadol is a painkiller many people take without knowing it could trigger a seizure-even at normal doses. If you or someone you care about has a history of seizures, epilepsy, or even just a single past seizure, this isn’t just a warning you can ignore. It’s a hard stop. Tramadol doesn’t just carry a risk-it actively lowers your brain’s natural defenses against seizures, and that danger doesn’t only come from taking too much.

How Tramadol Triggers Seizures

Most opioids, like morphine or oxycodone, don’t typically cause seizures. In fact, some can even reduce seizure activity at low doses. Tramadol is different. It works in two ways: as a weak opioid and as a serotonin-norepinephrine reuptake inhibitor (SNRI). That second part is the problem.

By blocking the reuptake of serotonin and norepinephrine, tramadol floods the brain with these chemicals. Too much serotonin, especially when combined with other drugs like antidepressants, can overexcite nerve cells. At the same time, tramadol and its main metabolite, M1, interfere with GABA-the brain’s main calming neurotransmitter. Less GABA means less inhibition, and that’s how seizures start.

Studies show that even at the lowest prescribed dose-75mg per day-seizures have occurred. One patient with no prior history took tramadol for back pain and had a tonic-clonic seizure within 12 hours. Another, who’d been on tramadol for months without issue, had a seizure after a small dose increase. It doesn’t matter if you’re taking it as directed. If your brain is already prone to overexcitability, tramadol can push it over the edge.

Who’s at the Highest Risk?

The risk isn’t the same for everyone. Data from a 3-year study of 28 patients with tramadol-induced seizures found that 92.8% were male, with an average age of 28.4. But that doesn’t mean women are safe-7.2% of cases were in women. Age isn’t the only factor. People with kidney problems are at much higher risk because tramadol builds up in the body when the kidneys can’t clear it. One patient with renal failure had a seizure after receiving 300mg intravenously-far below the overdose threshold, but dangerous because their body couldn’t process it.

Other high-risk groups include:

• People with a history of seizures or epilepsy
• Those taking SSRIs, SNRIs, or tricyclic antidepressants
• Patients using antipsychotics or other seizure-lowering drugs
• People who drink alcohol regularly
• Those who’ve used illicit stimulants like cocaine or MDMA

One case from New Zealand’s adverse drug reporting system involved a patient on a tricyclic antidepressant who had four seizures after tramadol doses were increased. Another patient with a known seizure disorder saw their seizure frequency spike within 24 hours of starting tramadol-even without any other medications.

It’s Not Just About Overdose

Many assume seizures only happen with abuse or overdose. That’s false. The maximum recommended daily dose of tramadol is 400mg. But seizures have been reported at doses as low as 75mg. In fact, the majority of cases-89.3%-happened within the first 24 hours of taking tramadol, even when the dose was within guidelines.

What’s more, tramadol’s effects aren’t linear. At low doses, it may actually have a mild anti-seizure effect in animal studies. But once you cross a certain threshold-usually between 200mg and 400mg-it flips. The brain’s balance tips, and seizures become likely. This makes it impossible to predict who will react badly. Two people taking the same dose-one might be fine, the other could seize.

Drug Interactions Make It Worse

Tramadol doesn’t exist in a vacuum. Over half of the seizure cases in the 2013 study involved people taking other drugs at the same time. The most dangerous combinations:

• SSRIs and SNRIs (like fluoxetine, sertraline, venlafaxine): These also raise serotonin levels. Combine them with tramadol, and you’re stacking the deck for serotonin syndrome and seizures.
• Tricyclic antidepressants (like amitriptyline): These are especially risky. Three patients in the Medsafe report had seizures while taking both TCAs and tramadol.
• Antipsychotics (like quetiapine, risperidone): They lower seizure threshold on their own. Add tramadol, and the risk multiplies.
• Alcohol: Even moderate drinking increases seizure risk with tramadol. The brain is already suppressed by alcohol, then suddenly overstimulated by tramadol’s effects.

One patient took tramadol with pethidine and cyclizine-an unusual combo-and had a seizure. Another took it with an SSRI and an antipsychotic. These aren’t rare cases. They’re red flags.

What Do Doctors Say?

Major medical institutions are clear: tramadol is contraindicated in patients with seizure disorders. The UCSF Pain Management Education program states it bluntly: don’t use it. The FDA’s own reclassification of tramadol as a Schedule IV controlled substance in 2014 was driven in part by rising seizure reports. The New Zealand Medsafe report from 2013 found tramadol was the most common drug linked to seizures in their database between 2001 and 2006.

Neurologists at Neurology.org confirmed that tramadol and its M1 metabolite reduce GABA activity-a direct, measurable mechanism for seizure triggering. And while most seizures from tramadol are short-lived and self-limiting, they can still lead to injury, hospitalization, or even sudden unexpected death in epilepsy (SUDEP) in vulnerable patients.

What Should You Do?

If you have a seizure disorder:

1. Do not take tramadol-even once. Not for a bad back, not for a toothache, not even if your doctor says it’s "safe."
2. Ask for alternatives: acetaminophen, ibuprofen, gabapentin, or non-opioid pain management plans.
3. If you’re already taking tramadol, don’t stop suddenly. Talk to your doctor about tapering safely.
4. Bring a list of all your medications to every appointment-including over-the-counter and supplements.

If you’re a caregiver or family member:

• Watch for sudden muscle jerks, loss of awareness, or unusual behavior after someone takes tramadol.
• Keep emergency contacts handy and know the signs of a seizure.
• Never assume "it’s just one time"-seizures can happen on the first dose.

What Are the Alternatives?

There are plenty of safer pain options if you have a seizure history:

• Acetaminophen (paracetamol): First-line for mild to moderate pain. No seizure risk.
• Ibuprofen or naproxen: Good for inflammation-related pain. Avoid if you have kidney issues.
• Gabapentin or pregabalin: Used for nerve pain and sometimes epilepsy. Safe in seizure patients.
• Physical therapy, acupuncture, or TENS units: Non-drug options that work for chronic pain.

For severe pain, some doctors may consider short-term use of morphine or oxycodone-but only after careful review. These still carry risks, but they don’t lower the seizure threshold the way tramadol does.

Final Warning

Tramadol is not a "safer opioid." That myth got people hurt. It’s not just about addiction. It’s about brain chemistry. One dose can be enough to trigger a seizure in someone with even a single past episode. The data is clear. The guidelines are strict. And the consequences can be life-changing.

If you’ve been told tramadol is "fine" for your pain, get a second opinion. Your brain isn’t worth the gamble.