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LayoutAnti-epileptic drugs: how they treat
seizures and their unwanted side-effects
AEDs for treating these different seizures or syndromes: Approximately 65-75% of people with tuberous sclerosis The specialist doctors (called paediatric or adult (TS) will have epilepsy. Most epilepsy starts in children neurologists) who treat people with TS and epilepsy will and there are many different types of epilepsy (see: prescribe the AED that is best for the type of epilepsy 'Tuberous sclerosis and epilepsy'). The vast majority of syndrome or type of seizure(s) that your child has. The people who have epilepsy will take antiepileptic drugs specialist will also take into account the possible (AEDs) - also called anticonvulsants - to try and control the unwanted side-effects of these medications as well as how seizures. The epilepsy that occurs in people with TS is the medications come. Anti-epileptic drugs may come as often difficult to control. This is particularly true if the tablets, capsules, flavoured liquids or powders that can be epilepsy starts in early childhood or the person had dissolved in water or juice. The specialist epilepsy doctor moderate or severe learning difficulties.
or nurse will explain how to give the medicine(s).
It may take a while to find the right medicine or amount It is important that people always receive the same brand (dose) of a medicine that works best for the person, of the antiepileptic medicine because different brands are whether a child or adult. Sometimes children and even not always the same. It is important for parents and some adults will need to take a combination of two AEDs - patients to keep a note of which brand(s) they take and to and this is called polytherapy. It is very rare for anyone to show this to the local chemist or pharmacy when need treatment with more than two AEDs at the same time.
collecting the next supply so that they receive the same There is no good scientific evidence that three AEDs will control seizures better than two. Also, people taking three AEDs are far more likely to have unwanted side-effects Some medicines that you may get on prescription or buy from the combinations of the different medications.
from a pharmacy do not work properly if taken with anti- epileptic drugs. Also, some medicines for epilepsy work Which anti-epileptic drug (AED)
less well if taken with other drugs. It is therefore important The choice of AED depends on the type of seizure or the to check with a pharmacist or doctor before giving other type of epilepsy (the epilepsy syndrome) the person has.
medicines to your child.
The simple guide below shows the most commonly used Seizure type (epilepsy syndrome)
First choice AED
Other AEDs that are used
Infantile spasms (West syndrome) Focal (partial seizures) Generalised tonic-clonic Sodium valproate Sodium valproate Clobazam / clonazepam Sodium valproate Lennox-Gastaut syndrome Sodium valproate Anti-epileptic drugs: how they treat
seizures and their unwanted side-effects
Some medications such as the oral contraceptive pill may with TS. One of the main side-effects of clobazam and also interact with some of the AEDs. This could mean that clonazepam is something called 'tolerance'. This means the oral contraceptive may not be as effective. The AEDs that over many weeks, sometimes months, these AEDs do that are known to reduce the effect of the oral not work as well. When the dose is increased seizure contraceptive pill include: control might improve a little but the person is more likely to become very sleepy. If this happens, the clobazam or clonazepam will usually be slowly discontinued.
Corticosteroids (prednisolone, ACTH, tetracosatide,
hydrocortisone) these are not proper anti-epileptic
drugs. Doctors are not sure why these medications work in some types of seizure - but they can do! They are used in only two situations. The most common reason for using a corticosteroid is to treat infants and young children with Many medicines used to treat epilepsy have some infantile spasms (West syndrome). The other situation is in unwanted sideeffects for the first few days or weeks. To the rare type of epilepsy called 'non-convulsive status keep this to a minimum the person will usually start by epilepticus'. Prednisolone and hydrocortisone are given taking a small amount (dose) of the AED and then the dose by mouth. ACTH and tetracosactide are given by will be gradually increased. The medication may be taken intramuscular injection which can be painful for the infant.
once a day to begin with but after a week or so it is usually Corticosteroids are usually given for a very short time and given twice a day. This means that the person may usually for no more than 4 or 6 weeks, sometimes less.
continue to have some seizures for a week or two until the This is because of side-effects associated with these AED is at the right dose. Some AEDs have to be started medications some of which can be very serious. These and increased very slowly and this is particularly the case include the following: irritability, hyperactivity, increased for lamotrigine and carbamazepine.
appetite and weight gain, disturbed sleep, high blood Fortunately most unwanted side-effects are mild and do pressure and a lowered resistance to fight severe not last long. The most common ones include sleepiness infections (called 'immunosuppression').
or drowsiness and occasionally nausea or vomiting Diazepam (Diazemuls; Diazepam Rectubes, Stesolid)
(feeling or being sick). Rarely, some people may also This is another type of benzodiazepine (like clobazam). Its complain of feeling rather bad-tempered. These side- only use in the treatment of epilepsy is an emergency effects usually wear off after a week or two.
situation. It is used to try and stop a tonic-clonic seizure More serious side-effects include a rash and this is that has been lasting for more than 5 minutes or to stop particularly likely with the AEDs lamotrigine (the brand repeated seizures that have been happening for 30 name of which is Lamictal), carbamazepine (the brand minutes. It can be given out of hospital and also in name is Tegretol), oxcarbazepin(the brand name is hospital. It comes in a tube (called a Diazepam Rectube or Trileptal) and phenytoin (the brand name is Epanutin - but Stesolid) and is squirted up the back passage (the this AED is used only very rarely now). It is important to rectum). In hospital it can be given this way but it can also understand that this rash will only occur in 5 to 8 out of be given by intravenous injection. Diazepam causes every 100 people who take these AEDs. It is also important sleepiness and most people will fall asleep after they have to stop taking the AED and to seek urgent medical advice been given it. Midazolam has largely replaced diazepam if a rash does occur within the first few weeks of taking to try and stop seizures out of hospital (midazolam is one of these medications.
described a bit later).
The following outlines the most commonly-used Ethosuximide (Zarontin; Emeside)
antiepileptic drugs and their most common side-effects This medication is used only to treat absence seizures and this seizure type is very unlikely to occur in TS. It has no Carbamazepine (Tegretol and Tegretol Retard)
effect on focal or tonic-clonic seizures and is only really The main unwanted side-effects are caused by starting the prescribed to children. The main side-effects are nausea drug in too high a dose and can be prevented if it is and diarrhoea and also a constant, but mild headache.
started slowly and increased over at least 3 to 4 weeks.
These side-effects go away when the medication is slowly The most common is a rash which affects the whole body but goes away once the drug is discontinued. Other quite common unwanted side-effects include drowsiness, feeling sick (nausea), seeing double (diplopia), poor co- This is not felt to be a particularly powerful AED, but it can ordination and headaches. A very rare side-effect is a be effective in treating focal (partial) seizures. It does have lowered immunity to fight infection because the very few side-effects and the main ones are behavioural medication can lower the white cells in the blood which changes (which occur in about 10 in every 100 people fight infections.
treated with this medication) and occasionally some abnormal movements. The other main problem with this Clobazam (Frisium) and clonazepam (Rivotril)
medication is that it often has to be taken three times a These belong to a group of AEDs called the day. Nearly all the other AEDs can be taken twice, or 'benzodiazepines'. Diazepam, lorazepam, midazolam and sometimes, just once a day.
nitrazepam are also benzodiazepines (these AEDs are described a bit later). The benzodiazepines can be very effective AEDs in treating different types of seizures This one of the newer AEDs and is effective in treating including myoclonic, atonic, focal (partial) and tonic- focal (partial) and generalised tonic-clonic seizures. There clonic seizures. Clobazam is used more frequently than is not enough information about whether it might be clonazepam because it is better at controlling focal and effective in the treatment of other types of seizure. The tonic-clonic seizures. The main side-effects of clobazam main sideeffects of lacosamide are dizziness and nausea and clonazepam include sleepiness and unsteadiness (feeling or being sick) which are more likely to occur if which usually wear off after a couple of weeks.
the person is also taking carbamazepine or Clonazepam can also cause excessive drooling, oxcarbazepine at the same time. The dizziness is thought excitement and hyperactivity, particularly in children.
to affect between 10 and 15 in every 100 people who take Because of this clonazepam is used only rarely in children Anti-epileptic drugs: how they treat
seizures and their unwanted side-effects
This has very few unwanted side-effects. The main one is a This is one of the oldest AEDs and although it is quite a rash which usually occurs within the first three weeks after powerful medication it is used only very rarely in Great starting the drug. This could be serious and if it does Britain - and hardly ever in children with TS. The occur, no more of the drug should be given until the medication is associated with many unwanted side- person has been seen urgently by their GP or in the local effects. These include an allergic rash, unsteadiness, Accident and Emergency Department. If used in high abnormal movements, nausea (feeling sick) and double doses it may cause headaches and difficulty sleeping. The vision. When used for many months or years it can also effect of lamotrigine is reduced if the person is pregnant called thickening of the gums and unhealthy teeth, or is taking the oral contraceptive. Lamotrigine may also roughening of the skin of the face and vitamin D interact with carbamazepine and sodium valproate, two of deficiency which leads to weak bones (called the most common AEDs that are often used to treat 'osteoporosis' or 'osteopaenia'). Phenytoin also affects the developing baby during pregnancy and cause malformations such as spina bifida, cleft lip and palate This is quite a new AED and seems to have very few and heart defects. Phenytoin also reduces the effect of the unwanted side-effects. As with most AEDs, people may oral contraceptive pill. Finally, people who take phenytoin complain of some sleepiness when it is first started but will usually need to have blood tests to measure the level this wears off. The other main side-effect is behaviour of the medication in the blood.
change causing irritability and bad-temperedness.
However, this only occurs in 8 or 10 out of every 100 who This AED is very similar to gabapentin. An additional take this medication.
unwanted side-effect is an increased appetite. Rufinamide (Inovelon): this is a very new AED and is mainly used in This is another type of benzodiazepine (like clobazam). It children with the type of epilepsy called the Lennox- is only used in epilepsy to treat a tonic-clonic seizure that Gastaut syndrome. It is effective in stopping the 'drop has lasted longer than 5 minutes and in hospital. It is given attacks' in this epilepsy that are caused by atonic and tonic by intravenous injection. In the future lorazepam may seizures. However, rufinamide might also be effective in become available as a very thin tablet or 'wafer' that is put treating focal (partial) seizures. The main side-effects are under the tongue and that melts rapidly to stop a tonic- vomiting and diarrhoea and also sleepiness and clonic seizure at home. Its main side-effect is sleepiness behaviour changes. More information is still needed on and many people will fall asleep after it has been given.
this AED because it has only been used in Great Britain for the past few years.
Midazolam (Epistatus; Hypnovel)
This is another type of benzodiazepine (like clobazam, Sodium valproate (Epilim; Epilim Chrono; Episenta)
diazepam and lorazepam). Its only use in the treatment of This is one of the most effective and also the most epilepsy is to try and stop a tonic-clonic seizure that has commonly used AED in Europe. When used alone it been lasting for more than 5 minutes or to stop repeated causes very few unwanted side-effects. The main side seizures that have been happening for 30 minutes. It can effects are some sleepiness or irritability (mainly in be given out of hospital and in hospital. It is given into the children) as the medication is first started. It canfrequently cheek cavity (called the buccal cavity) - which is the increase a person's appetite leading to an increase in space inside the cheek. It is not pout into the mouth. The weight. This is more commonly seen in girls and young main side-effect is sleepiness and most people will fall women rather than in boys. The medication can also cause asleep after it has been given.
some hair loss in the first six months after it has been started. The hair always grows back and when it does it is usually thinner and curlier. High doses of the medication This is another type of benzodiazepine (like clobazam, may also cause a tremor (shakiness). There is a very rare lorazepam and midazolam). It is only really used to treat side-effect of liver damage in young children aged less the seizure type, infantile spasms. In infants less than 12 than 3 years who have a biochemical (metabolic) cause months of age infantile spasms is the type of seizure that for their epilepsy. This risk of liver damage does not seem occurs in West syndrome. The medication can also be to be a problem in young children with TS. The main used sometimes to treat epileptic spasms that occur in unwanted sideeffects are in older girls and young women.
older children. The main side-effects of this AED are It may cause problems with the menstrual cycle (periods) sleepiness and excessive drooling. Most children who and might affect the developing baby during pregnancy receive this medication do so for 6 to 12 months.
resulting in malformations. This is more likely if sodium valproate is taken at the same time as other AEDs. These are very important side-effects. Because of this, the use of This is very similar to carbamazepine (Tegretol) that has valproate must be carefully considered and discussed been described earlier. Oxcarbazepine is considered to with females of child-bearing age and potential.
have similar but less frequent fewer side-effects than carbamazepine. However, oxcarbazepine does not come as in a slow-release tablet and so it will always have to be This is an old AED that is used a lot in Germany, Austria given twice, or rarely, three times a day.
and other European countries. It is only rarely used in Great Britain. It is useful in treating focal (partial) seizures and some people with tonic-clonic and myoclonic This is the oldest AED and although it may be effective in seizures. There are only a few unwanted side-effects such treating tonic-clonic, atonic and myoclonic seizures it is as sedation and rarer side-effects including hyperpnoea rarely used today. It is only really used as an anti-epileptic (breathing more rapidly) and some mental slowing.
drug of last choice - when the other AEDs have not worked. The main side-effects are an allergic rash, sleepiness, hyperactivity and mental slowing (which can This can be an effective medication in stopping seizures.
be a big problem for school children), and weak bones Unfortunately, it may cause a number of unwanted side- (called 'osteoporosis' or 'osteopaenia'). The medication effects. The main ones are a reduction in appetite which, in reduces the effect of the oral contraceptive pill and may children can lead to some weight loss which might affect cause malformations of the developing baby during their growth. The other side-effects include mental slowing which means that people may not be able to think Anti-epileptic drugs: how they treat
seizures and their unwanted side-effects
or talk as well. This can affect up to 20 in every 100 people who take the medication. The other side-effect is on The main side-effect is dizziness and nausea. Rarely it my behaviour making some people angry or very sad and make some seizures worse - particularly myoclonic and this happens in 5 or 10 out of every 100 people on this absence seizures.
AED. All of these side-effects will go away when the medication is slowly withdrawn. The last and least New anti-epileptic drugs
common side-effects are kidney stones and pressure in There are also some brand new AEDs that have recently the eye (called 'glaucoma').
become available and there is not much information on these medications.
This medication is mainly used in treating children who have infantile spasms (West syndrome). Vigabatrin is Eslicarbazepine (Zebinix): probably similar to actually the medication of first choice in treating children carbamazepine and oxcarbazepine in how it acts and its with infantile spasms caused by TS. The main unwanted side-effects. This AED may only need to be given once a side-effects in treating infantile spasms are sleepiness and irritability - but these usually wear off after a few days.
Retigabine (Trobalt): no information on this AED Rarely, the medication may also increase the child's appetite. It may also worsen some other seizure types - Information about the practical aspects of giving anti- particularly myoclonic seizures. Vigabatrin also used to be epileptic drugs to children and all the likely side-effects prescribed for focal (partial) seizures but because of one that may occur with the different AEDs can be found at the particular side-effect it is far less commonly used. This following website: side-effect is reduced peripheral vision so that a person may have difficulty seeing things at the edge of their vision. It is recommended that if a person is to take Much more detailed, but sometimes difficult to read vigabatrin then their peripheral vision (visual fields) information, can be found with the information leaflet that should be examined before starting the drug and every 4 comes with the medicine.
to 6 months whilst they remain on it. Children who have learning difficulties are not usually able to have this test because it requires concentration and co-operation.
This is quite a new AED to be used in Great Britain. It seems to be effective in a wide range of different types of seizure. It is quite similar to topiramate which has been described earlier. However, zonisamide has fewer unwanted sideeffects and particularly causes less mental slowing and behaviour changes than topiramate.
Zonisamide may also cause kidney stones.
Other, less commonly used anti-epileptic
There are a number of other AEDs that may be used in treating people with epilepsy and TS. They are only prescribed in certain situations.
This is a very weak AED and is only used in conjunction with either carbamazepine or oxcarbazepine. Side-effects are uncommon and include nausea, reduced appetite and Dr Richard E. Appleton
occasionally, tingling in the fingers and toes. Paraldehyde: this is a very old anticonvulsant that is now only used very Consultant Paediatric Neurologist rarely and mainly in children. It is only ever used to try The Roald Dahl EEG Unit and stop a tonic-clonic seizure that has been lasting for Paediatric Neurosciences Foundation more than 5 minutes or to stop repeated seizures that have Alder Hey Children's Hospital been happening for 30 minutes. It comes as a ready-made mixture with olive oil and is squirted up the back passage (rectum). It has a very powerful smell and causes children August 2011
to sleep after it has been given. It is far less commonly used instead of a benzodiazepine (midazolam or diazepam) as the child's emergency (also called 'rescue') medication. It can also be used in hospital.
Further information on TSC and the work of the Tuberous This medication is mostly used for a quite rare epilepsy Sclerosis Association can be obtained from our website at: syndrome called Dravet syndrome (also known as 'severe myoclonic epilepsy of infancy'). However, it may occasionally be used to treat myoclonic and tonic-clonic While every effort is made to ensure that our publications are correct, seizures in different epilepsy syndromes. It does have a please note that some information may change after the date of printing.
few unwanted side effects including sleepiness during the Information in this leaflet is not intended to be a substitute for medical day but insomnia (difficulty falling asleep) at night. It can advice from your own doctors, who know your individual circumstances.
also cause a loss of appetite and some behaviour We strongly recommend you talk to your doctor, and share the above problems. As will all the AEDs, these side-effects go when information. The TSA cannot be held responsible for any actions taken as a stiripentol is gradually discontinued.
result of using TSA information resources. Tuberous Sclerosis Association is a Company Limited by Guarantee Registered in England and Wales No. 2900107 English Registered Charity Number. 1039549 Scottish Registered Charity No. SC042780 Registered Office: Abertawe House, Ystrad Road, Fforestfach, Swansea, SA5 4JB
Alzheimer's Imaging Consortium IC-P: Poster Presentations Background: Rosiglitazone, a peroxisome proliferator-activated receptor copy. Because of their high iron content, plaques typically appear as hypo- [gamma] (PPAR[gamma]) agonist, has an anti-inflammatory effect in the intense spots on T2-weighted scans. One of the challenges in imaging brain, decreasing interleukin-1[beta] concentrations in hippocampus and re-