Epilepsy Medications: Choosing, Taking and Living With Them

Epilepsy medications: why the right drug depends on the seizure type

Between 60 and 70 per cent of Australians with epilepsy become seizure-free on medication, frequently on the first or second drug tried and frequently within a year. Medication is the most successful intervention in epilepsy by a wide margin, and the headline figure deserves saying first because the rest of this guide is about complications.

Two things then go wrong often enough to be worth a guide.

The first is the wrong drug for the seizure type. Anti-seizure medications are not interchangeable. Some drugs that work well for focal seizures make generalised seizures worse — carbamazepine can aggravate absence and myoclonic seizures, and a person with juvenile myoclonic epilepsy started on it can deteriorate while appearing to be treated. Getting the seizure type and syndrome right is what prevents that, which is why seizure types and diagnosis come before this guide rather than after it.

The second is the side effects, which are under-discussed to a degree that surprises people. Medication is the largest single item in the Australian health system cost of epilepsy — $262.1 million a year, more than acute hospital care — and the effects on mood, memory, concentration, bone health and pregnancy are real, common and frequently attributed to the epilepsy instead of the drug.

This guide covers how medication is chosen, the main drugs and what distinguishes them, side effects including the serious ones, adherence, interactions, stopping, and what to ask at a review.

One rule before anything else: never stop or change an anti-seizure medication without specialist advice. Abrupt withdrawal can provoke seizures, including status epilepticus. The Epilepsy Foundation’s own guidance puts it plainly — under no circumstances should a dose be altered without specialist advice. If a side effect is intolerable, that is a reason to ring your prescriber today, not to stop the tablets tonight.

How a medication gets chosen

Four things drive the decision, and understanding them makes the conversation with a neurologist more useful.

The seizure type and syndrome. The dominant factor. Broadly:

Focal seizures respond to a wide range — carbamazepine, oxcarbazepine, lamotrigine, levetiracetam, lacosamide, sodium valproate, topiramate, zonisamide, perampanel, brivaracetam.

Genetic generalised epilepsies (including juvenile myoclonic epilepsy and childhood absence epilepsy) have a narrower list, and this is where drug choice can do harm. Sodium valproate is the most effective, which creates a genuine dilemma for people who may become pregnant. Lamotrigine and levetiracetam are the usual alternatives. Ethosuximide is specifically for absence seizures.

Drugs that can worsen generalised seizures include carbamazepine, oxcarbazepine, phenytoin, gabapentin and pregabalin. Lamotrigine, although widely used, can occasionally worsen myoclonic seizures.

Specific syndromes have specific answers. Dravet syndrome is a clear example where certain drugs are avoided and others are indicated, which is part of why genetic testing has become standard in severe early-onset epilepsies.

The person. Age, sex and childbearing potential, weight, mood history, other medical conditions, kidney and liver function, occupation, and whether they will reliably take something three times a day.

The side effect profile matched to the person. A drug that causes weight gain, one that causes weight loss, one that can worsen depression, one that can cause behavioural change in children, one that affects word-finding — these are choices, and a good prescriber makes them with the person rather than for them.

And interactions, particularly with hormonal contraception, which is covered below and which catches people out in both directions.

The main medications, in plain terms

Not a complete list, and not a recommendation — your neurologist chooses for your epilepsy. This is to help you know what you are taking and what to watch for.

Levetiracetam (Keppra). Very widely used. Broad spectrum, works for focal and generalised seizures, few drug interactions, can be started quickly, and is one of the safer options in pregnancy. The thing to know: behavioural and mood side effects — irritability, anger, low mood, sometimes significant — are common enough to have a nickname among patients. They are dose-related and frequently resolve on switching. If somebody becomes short-tempered or depressed after starting levetiracetam, that is the drug talking and it should be reported rather than endured.

Lamotrigine. Broad spectrum, generally well tolerated, mood-neutral or mood-positive for many people, and one of the preferred options in pregnancy. The things to know: it must be titrated up slowly over weeks because of the risk of a serious rash, and that slow titration means it does not suit a situation needing rapid control. Its levels are substantially affected by hormonal contraception and by pregnancy — see below.

Sodium valproate (Epilim). The most effective drug for genetic generalised epilepsies and a mainstay for decades. The things to know: significant teratogenic risk, with malformation rates running about 3.3 per cent at daily doses below 1100 mg and about 30.2 per cent at 1100 mg or above, plus neurodevelopmental risks. Also weight gain, tremor, hair thinning, and rarely liver or pancreatic problems. Australia has deliberately not adopted the UK’s restrictions, which is a contested decision explained in women and epilepsy.

Carbamazepine (Tegretol). Effective for focal seizures. The things to know: it can worsen generalised seizures; it is a strong enzyme inducer so it interacts with a long list of other drugs including hormonal contraception; it affects vitamin D and bone health over years; and it carries a risk of serious rash, with higher risk in people carrying the HLA-B*1502 allele, which is more common in some Asian populations and which is worth asking about.

Oxcarbazepine. Similar to carbamazepine with fewer interactions, but can cause low sodium, particularly in older people.

Phenytoin (Dilantin). Older, effective, still used in emergencies. Long-term it causes gum overgrowth, coarsening of facial features, hair growth, and cerebellar effects, and it has unpredictable dose-level behaviour. Rarely a first choice now in ongoing treatment.

Topiramate. Effective, also used for migraine. The things to know: word-finding difficulty and cognitive slowing are common and are the commonest reason people stop it; also weight loss, tingling in the hands and feet, kidney stones, and teratogenic risk.

Sodium channel blockers more broadly — lacosamide, which is well tolerated and increasingly used for focal seizures.

Ethosuximide, for absence seizures specifically.

Clobazam and clonazepam, benzodiazepines used as add-ons, effective but with sedation and tolerance over time.

Perampanel, brivaracetam, zonisamide, eslicarbazepine — newer agents used mainly as add-ons in difficult epilepsy.

Cannabidiol (Epidyolex), approved for specific severe childhood epilepsies including Dravet and Lennox-Gastaut syndromes. Worth distinguishing clearly from over-the-counter CBD products, which are a different thing entirely. Availability and subsidy arrangements change, so ask your clinic what currently applies.

Midazolam, as buccal or intranasal emergency medication for prolonged seizures, under a written plan. Covered in epilepsy and seizure support.

Side effects, including the ones nobody mentions

The general ones, dose-related and often settling after a few weeks: drowsiness, dizziness, unsteadiness, double vision, nausea, headache.

The cognitive ones, which matter more than their profile suggests. Slowed thinking, poor concentration, word-finding difficulty, memory complaints. These get attributed to the epilepsy and are frequently the medication, and the distinction is testable — by reducing the dose, or switching, and seeing what changes. People spend years assuming their memory is the epilepsy when it is the topiramate.

The mood ones. Several anti-seizure medications can cause or worsen depression, irritability and anxiety; levetiracetam is the most commonly implicated. In a population where depression already affects a substantial proportion, a drug-induced contribution is worth looking for before concluding it is the condition.

Bone health. Long-term use of enzyme-inducing drugs — carbamazepine, phenytoin, phenobarbitone — and valproate is associated with reduced bone density and increased fracture risk. This is a long-term consequence that nobody mentions at the start. Ask about vitamin D levels and bone density if you have been on these drugs for years.

Weight. Valproate, pregabalin and gabapentin tend to cause gain; topiramate and zonisamide tend to cause loss.

And the serious ones, which are rare and which you should know the warning signs for:

Serious rash. Any rash in the first eight weeks of starting a new anti-seizure medication, particularly lamotrigine or carbamazepine, needs same-day medical assessment. A rash with fever, blistering, mouth or eye involvement, or feeling generally unwell is an emergency. These reactions are rare and they are the reason lamotrigine is titrated so slowly.

Liver problems, with valproate particularly: vomiting, abdominal pain, jaundice, lethargy.

Low sodium, with oxcarbazepine and carbamazepine: confusion, nausea, headache, worsening seizures.

Suicidal thoughts, which carry a warning across the class and which should be reported immediately rather than waited out.

And a general principle: if something changed after a medication started or a dose increased, suspect the medication. Report it. Most side effects are manageable by adjusting dose, changing timing, or switching drugs, and the alternative — stopping abruptly — is dangerous.

Adherence, honestly

Missed doses are one of the strongest modifiable risk factors for breakthrough seizures and for SUDEP. They are also extremely common, and the reasons are mundane rather than careless.

Why people miss doses: three-times-daily regimens, side effects, feeling well, running out of scripts, travel, shift work, cost, forgetting, and — frequently — not wanting to be reminded they have epilepsy.

What actually helps:

Simplify the regimen. Find out whether the drug comes in a once- or twice-daily form. Fewer doses reliably means better adherence.

Blister packs or dose boxes from a pharmacy, which also make it obvious whether a dose was taken.

A phone alarm tied to something you already do — brushing teeth, a meal.

A plan for the missed dose, agreed with the prescriber in advance, so you are not guessing at 11pm. The answer differs between drugs and between people.

A plan for vomiting, which is a genuine problem in a gastro illness and which nobody prepares for.

Never running out. Ask for repeats early. A weekend without medication is a real risk.

And telling the truth at appointments. A prescriber who believes a drug has failed when it was not being taken will escalate to a less suitable medication. Nobody is going to be cross; they need the information.

Interactions, particularly contraception

This catches people in both directions and it is one of the most consequential practical issues in epilepsy.

Enzyme-inducing anti-seizure medications reduce the effectiveness of hormonal contraception. Carbamazepine, oxcarbazepine, phenytoin, phenobarbitone, primidone and topiramate at higher doses all do this. The combined pill, the progestogen-only pill, the implant and the patch can all be affected, which means unintended pregnancy is a real risk in somebody who believes they are protected. The methods not affected by enzyme induction are the copper IUD, the hormonal IUD and the depot injection, which is why these are frequently recommended.

And it runs the other way. Oestrogen-containing contraception lowers lamotrigine levels, sometimes substantially, which can cause breakthrough seizures when a pill is started — and rising levels with side effects in the pill-free week or when it is stopped. This needs anticipating rather than discovering.

Oestrogen-containing contraceptives may also lower valproate levels, so clinical response should be monitored when one is started.

Other interactions worth knowing: enzyme inducers affect warfarin, some antidepressants, some antipsychotics, statins, and many other drugs. Valproate raises lamotrigine levels substantially, so lamotrigine doses are lower when the two are combined.

And drugs that lower the seizure threshold. Some antidepressants and antipsychotics can do this, which matters in a population where depression is common. It is generally still right to treat the depression — the risk is manageable and untreated depression is worse — but the choice of agent should be made by somebody who knows about both conditions.

The practical instruction: tell every prescriber and every pharmacist what you take, ask specifically about contraception if it applies, and ask for a medication review if you are on several things.

Stopping medication

Genuinely possible for many people, and worth asking about.

Epilepsy Action Australia notes that after two to five years seizure-free, medication can be withdrawn without later relapse in around 70 per cent of children and 60 per cent of adults. Those are good odds, and a significant number of people treat epilepsy for a period of their life rather than for all of it.

What it depends on: how long seizure-free, the epilepsy syndrome (some, like juvenile myoclonic epilepsy, usually require lifelong treatment), whether the EEG is normal, whether there is a structural lesion on MRI, age, and how much a recurrence would cost the person — somebody whose licence and job depend on seizure freedom may reasonably choose not to risk it.

How it is done: slowly, over months, under specialist supervision, with a plan.

And the driving consequence, which people are not told: you must not drive during the withdrawal or dose change, and for three months afterwards. Commercial drivers lose conditional licence eligibility if medication is withdrawn at all. See driving, work and independence.

What to ask at a review

“What is my seizure type and syndrome, and is this medication the right class for it?”

“Am I on an adequate dose, or is there room to increase?”

“Could any of my symptoms be side effects rather than the epilepsy?” Ask specifically about memory, concentration, word-finding and mood.

“Can I take this fewer times a day?”

“What do I do if I miss a dose, or vomit after taking one?” Get the answer written down.

“Does this interact with my contraception?” And if relevant: “Which contraceptive methods are reliable with this drug?”

“Should my vitamin D or bone density be checked?” Particularly after years on enzyme-inducing drugs or valproate.

“If I might become pregnant, is this the right drug for me?” Ask before a pregnancy, not during one.

“Have I tried two medications without seizure control?” Because if so, the answer is not a third drug. See drug-resistant epilepsy.

And ring a free epilepsy nurse. Epilepsy Action Australia on 1300 37 45 37 or the National Epilepsy Support Service on 1300 761 487. Medication questions are exactly what they are best at, and they have time a specialist appointment does not.

Generics, supply and the practical problems

The unglamorous end of medication management, where a surprising amount of harm occurs.

Generic substitution. Anti-seizure medications are one of the few drug classes where switching between brands genuinely matters to some people. Different formulations of the same drug can be absorbed slightly differently, and for a medication where a small change in blood level can mean a breakthrough seizure, that margin is narrower than for most drugs. Australian and international epilepsy bodies have generally advised consistency of brand for anti-seizure medications.

What to do about it: if a particular brand is working, ask your prescriber to note on the script that substitution is not appropriate, and ask the pharmacy to keep supplying the same one. If the pharmacy substitutes and seizures change, that is worth reporting rather than dismissing as coincidence.

Supply interruptions. Medicine shortages in Australia are more common than people expect and anti-seizure medications are not exempt. The protections are practical: order repeats two weeks early rather than on the last day, use the same pharmacy so they know your pattern and can order ahead, and if a shortage hits, ring the prescriber rather than accepting an unplanned switch or a gap. A different strength of the same drug is usually a better answer than a different drug, and both are better than nothing.

Travel. Carry medication in hand luggage, in original packaging, with a copy of the script and a letter from your doctor naming the medication and the condition — necessary for some countries and useful everywhere. Take more than the trip requires. Account for time zones by keeping dose intervals roughly constant rather than switching abruptly to local clock times. And check the legal status of your medication at the destination, because some common drugs are restricted in some countries.

Cost. Anti-seizure medications are PBS-listed, and the Safety Net reduces costs once annual thresholds are reached — worth asking the pharmacy to track, since they can record your spend. Where cost is causing people to skip doses or delay scripts, say so to the prescriber; there are frequently cheaper options within the same class.

And the vomiting problem. Nobody plans for a gastro illness, and a day of vomiting means a day without anti-seizure medication. Ask in advance what to do, because the answer differs by drug — and in some cases there is a dispersible or rectal alternative that can be kept at home for exactly this.