Antiepileptic drugs: review of safety of use during pregnancy

During the critical period, synapses that receive visual stimulation and pass on action potentials into the visual cortex are retained and strengthened. Synapses that do not receive visual stimulation, so the neurones between them are not firing, are removed. This means that if visual stimulation does not occur during the critical period (i.e. if a baby is born with cataracts which obscure vision or if they are born in a cave) then their visual cortex will not develop properly because many of the synapses will have been destroyed. Evidence for a ‘critical period’ comes from some ethically-dubious experiments on kittens (see below). The visual cortex is a region at the back of our brains and forms part of the cerebral cortex. Neurones in the visual cortex receive information from either our right or left eye and are clustered together in structures called ocular dominance columns.

• It’s important because it means that organisms don’t waste time and energy by responding to stimuli that do not pose a danger to them.
• Studies that explore a dose-dependent risk are very limited but where this was studied (Nulman et al 1997, Samren et al 1997, Kaneko et al 1999, Kaaja 2003, Hernandez-Diaz et al 2012) the data do not consistently show an association between dose and risk of major congenital malformations.
• The available clinical data examining the effect of topiramate on fetal loss are very limited and the findings are inconsistent (Ornoy et al 2008, Trivedi et al 2018, Vajda et al 2018, Veroniki et al 2017a).

Brain Architecture

Overall, the available data do not allow for robust conclusions to be drawn on the safety of use during pregnancy of brivaracetam, clobazam, clonazepam, eslicarbazepine, ethosuximide, lacosamide, rufinamide, perampanel, primidone, tiagabine and vigabatrin. The risks of major congenital malformations, neurodevelopmental disorders and delay, and other reproductive toxic effects remain uncertain; the possibility of adverse effects can neither be confirmed nor ruled out. Overall, the available clinical data do not indicate a negative impact of lamotrigine on these outcomes. For the majority of these drugs the data relating to safety of use during pregnancy remains limited or very limited. For perampanel, primidone and vigabatrin there are data on less than 300 exposed pregnancies and for brivaracetam, eslicarbazepine, ethosuximide, lacosamide, rufinamide, and tiagabine there are data on less than 100 exposed pregnancies.

Risk Ratio/Relative Risk

We are thus beginning to understand how our emotions connect to the well-being of ourselves and our loved ones, and most importantly we are learning that to change something outside of ourselves we first need to change something inside ourselves. When the whole cerebrumiq planet has learnt this, then the world will be a better place. When we have this congruence in our society then we will find it also in our children.

For pregabalin, there are emerging unpublished clinical data which are currently undergoing further evaluation but are suggestive of a possible slight increase in overall risk of congenital malformations. For gabapentin, the Marketing Authorisation holder has recently been requested to perform a population-based cohort study examining pregnancy outcomes, which ideally will include a sufficient number of exposed pregnancies to better inform our understanding of the risks to the unborn baby. The findings of both of these studies along with any other emerging data on safety of use during pregnancy of any of the antiepileptic drugs will be carefully evaluated as they become available.

Psychology Memory PowerPoints / Google Slides / Video Links / Guided Notes

A study that collects health information from women who take prescription medicines or vaccines when they are pregnant. A birth defect where a baby’s head is smaller than expected when compared with babies of the same sex and age. When an epileptic seizure starts in one side of the brain it’s called a focal onset seizure or a focal seizure; both terns mean the same thing. When person has no loss of awareness of their surroundings during it, it is called a focal onset aware seizure. When the person’s awareness of what is happening around them is affected at any time during the seizure, it’s called a focal impaired awareness seizure. The size of the baby’s head that can be measured during pregnancy and then compared to certain normal curves.

• Zonisamide is reported to be teratogenic in multiple animal species, both rodent and non-rodent at plasma concentrations relevant to the human therapeutic dose.
• These data suggest that there is substantial use in women of childbearing potential and also during pregnancy.
• Hubel and Wiesel carried out an experiment on kittens and adults cats in 1963 which proved that the visual cortex develops during a critical period early in life.
• The real power of the brain to tackle a task is unleashed when left and right brains work together simultaneously and synergistically.

Given the limited data, no firm conclusions can be drawn with regards to the safety of use of these antiepileptic drugs during pregnancy and the risks remain unclear. Non-clinical studies report reduced fetal body weights in rats and rabbits following exposure to pregabalin during pregnancy but this occurred at plasma concentrations sufficiently higher than human therapeutic concentrations. Dosing of pregabalin during gestation and lactation induced offspring developmental toxicity in rats at exposures 5 times or greater than the maximum recommended human exposure. A further study by Trivedi et al 2018 in the Kerala Pregnancy Registry investigated spontaneous fetal loss in pregnancies exposed to phenytoin compared with pregnancies in non-exposed women with epilepsy.

People with bipolar disorder have episodes of depression (feeling very low and lethargic) and mania (feeling very high and overactive). Unlike simple mood swings, each extreme episode of bipolar disorder can last for several weeks (or even longer). Autism is a lifelong developmental disability which affects how people communicate and interact with the world. Learning/memory impairments in rat offspring prenatally exposed to phenytoin.