Therapeutic Drug Monitoring in Pregnancy

Pregnancy can substantially change the blood concentration of several antiseizure medicines even when the dose has not changed.

Therapeutic drug monitoring can help maintain seizure control while avoiding unnecessary exposure, particularly for medicines whose clearance changes markedly during pregnancy.

Why pregnancy changes medicine levels

Pregnancy alters blood volume, kidney filtration, liver-enzyme activity, body composition and protein binding.

Different antiseizure medicines respond differently to these physiological changes.

The aim is usually the person’s own effective concentration

Pregnancy monitoring is not simply about keeping a laboratory result inside a population reference range.

Where possible, clinicians compare pregnancy levels with a pre-pregnancy baseline concentration measured while the person is seizure controlled on a stable dose.

Lamotrigine

Lamotrigine clearance commonly rises substantially during pregnancy.

The MONEAD study found dose-normalised lamotrigine concentrations fell by up to about 56% compared with postpartum values.

Some individuals experience even larger changes.

Levetiracetam

Levetiracetam concentrations also commonly fall because renal clearance increases during pregnancy.

MONEAD found dose-normalised concentrations decreased by about 37% compared with postpartum values.

A 2024 pregnancy cohort also demonstrated falling concentrations during pregnancy followed by a rapid postpartum rise.

Oxcarbazepine and its active metabolite

Concentrations of the active monohydroxy derivative can decrease during pregnancy.

Monitoring may therefore be useful when seizure control depends on stable exposure.

Lacosamide and zonisamide

MONEAD also identified substantial pregnancy-associated decreases in dose-normalised concentrations of lacosamide and zonisamide.

The evidence base is smaller than for lamotrigine and levetiracetam.

Carbamazepine

Carbamazepine pharmacokinetic changes are generally smaller and more complex because protein binding and active metabolites matter.

Total concentration alone may not always reflect pharmacologically active exposure.

Valproate

Valproate has major fetal risks and should be avoided during pregnancy when clinically feasible according to current international and national guidance.

If it must be continued, changes in protein binding make interpretation of total concentrations difficult; free valproate measurements may provide additional information.

When should a baseline be obtained?

Ideally, an individual reference concentration is established before conception when seizure control is stable.

If pregnancy begins before a baseline is available, early-pregnancy levels and previous clinical records may still help guide monitoring.

How often should levels be checked?

There is no single universal interval for every medicine and every pregnancy.

Published lamotrigine studies commonly used measurements every one to three months, while many specialist services monitor more frequently when concentrations are changing rapidly, seizures recur or doses are being adjusted.

Monitoring must start early

Clearance changes can begin in the first trimester.

Waiting until late pregnancy can miss an early fall in exposure.

Seizure control remains the priority

The 2024 AAN/AES/SMFM pregnancy guideline emphasises minimising convulsive seizures during pregnancy because they can harm both the pregnant person and fetus.

Once pregnancy has begun, abruptly withdrawing an effective antiseizure medicine can itself be dangerous.

Do not chase a number automatically

A lower level does not always require a dose increase.

Clinicians consider seizure history, the magnitude of concentration change, medicine-specific pharmacokinetics and adverse effects.

Postpartum is a critical period

Drug clearance can return toward pre-pregnancy levels quickly after birth.

If doses were increased substantially during pregnancy and are not reduced appropriately, concentrations can rise rapidly and cause toxicity.

Postpartum lamotrigine

Lamotrigine is particularly important because clearance can fall quickly after delivery.

Dizziness, diplopia, imbalance, nausea and other toxicity symptoms can develop if a pregnancy-increased dose is left unchanged.

Postpartum levetiracetam

Levetiracetam concentrations can also rise rapidly after birth as renal physiology normalises.

A 2024 study supports planned postpartum dose reduction and continued blood-level monitoring.

Breastfeeding

Postpartum dose planning and infant exposure are separate considerations.

Whether breastfeeding is appropriate depends on the specific antiseizure medicine and clinical circumstances; many commonly used antiseizure medicines are compatible with breastfeeding under appropriate supervision.

The central point

Pregnancy monitoring works best by comparing each person’s drug concentration with their own effective pre-pregnancy baseline, then continuing surveillance after birth as clearance rapidly normalises.

Sources

Safety note: antiseizure medicine doses should not be changed during pregnancy or postpartum without specialist clinical guidance.

Evidence checked: September 2026.