The Side Effects of Anti-Epileptic Drugs S E Essex Epilepsy Support group meeting Dr Ann Cheesman Neurology, Southend Hospital 14th March 2017

Numbers of People with Epilepsy Southend Hospital serves a population of 340,000 people Number of new people with epilepsy in UK : 50 per 100,000 per year → over 150 new patients per year in Essex region Number of people with epilepsy: 5-10 cases per 1000 equates to 1700-3400 cases We have 700 Epilepsy FU patients ie 1000-2500 are in Primary Care

Starting medication After 2 epileptic seizures separated by < 10 years (unless there are precipitating factors unlikely to be repeated) After the first seizure if there are likely to be further seizures eg. seizure several months after a traumatic brain injury Discuss risks and benefits Need a margin of protection

Actions of antiepileptic drugs GOOD Controlling seizures Some: reduce anxiety Some: help migraine UNWANTED SIDE EFFECTS Dizziness Drowsiness Weight gain

Choosing a drug The right drug for the type of epilepsy Avoid drugs with difficult S/Es for this patient eg Topiramate in a person with depression eg Sodium Valproate in an overweight person Are there S/Es which would be useful? eg Topiramate in a person with migraine eg Topiramate in an overweight person

Women & Epilepsy Drugs: issues Contraception: Lamotrigine reduces Oestrogen levels from the pill Foetal malformations: Increased with multiple medications and higher doses AVOID Valproate unless essential Pregnancy: Folic Acid 5mg od throughout fertile years Continue medication Lamotrigine may need to be increased Child cognition Dose-related reduction in IQ with Valproate UK Epilepsy and Pregnancy Register www.epilepsyandpregnancy.co.uk/

Major congenital malformation rate (%) by drug dose.  Major congenital malformation rate (%) by drug dose. CBZ, carbamazepine; LTG, lamotrigine; VPA, valproate. Morrow J et al. J Neurol Neurosurg Psychiatry 2006;77:193-198 ©2006 by BMJ Publishing Group Ltd

Foetal valproate syndrome

How do drug levels vary in the blood? American Epilepsy Society 2011

Side Effects Acute: Chronic: “Out of the blue”: related to the drug levels eg. max an hour after drug Reversible- go away when the drug is stopped Chronic: Related to chronic use Reversible or irreversible “Out of the blue”: Bone marrow effects

Acute Side Effects Rash 10% with Lamotrigine Blurred vision Tiredness

Nerves - sensation and balance Longterm Side Effects Bone including vitamin D Carbamazepine/Oxcarbazepine Phenytoin Sodium Valproate Gum and skin changes Phenobarbital Nerves - sensation and balance Carbamazepine

Bone Side Effects Ask whether you should be on Vitamin D?

Gum Side Effects Mainly Phenytoin Need folic acid

Nerves Balance- reversible except mainly Phenytoin

Thank you! … Any questions?

Drug choices Carbamazepine, Oxcarbazepine Sodium channel inhibition Carbamazepine, Oxcarbazepine Lamotrigine (+ glut reduction) Topiramate (+ glut reduction & CACN moduln) Phenytoin Lacosamide- need ECG GABA augmentation Sodium valproate Clobazam, Lorazepam Phenobarbital Synaptic vesicle protein modulation Levetiracetam (Ca channel modulation) Gabapentin, Pregabalin AMPA receptor antagonist Inhibits fast glutamate post-synaptic excitation Perampanel