How the effectiveness of Antiepileptic Drugs in Adults Predict same result in Children?
This is very nice researches that will guide us to use new Antiepileptic Drugs in kids as we are using to adults.
What are Antiepileptic Drugs?
The anticonvulsants (also commonly known as antiepileptic drugs) are a diverse group of pharmaceuticals used in the treatment of epileptic seizures.
There is no formula to choose which seizure medicine to use for a particular patient. No one medicine dominates for effectiveness, and all have various side effects. Doctors and patients choose AEDs after considering which side effects should be avoided in particular cases, convenience of use, cost and physician experience. An important start is to know which AEDs work for which seizure types. The narrow spectrum AEDs mostly work for specific types of seizures (such as partial, focal, or absence, myoclonic seizures). Broad spectrums AEDs additionally have some effectiveness for a wide variety of seizures (partial plus absence myoclonic seizures). Some types of seizure are difficult to treat with any AED. (Go here to learn what these seizures types are).
Narrow-spectrum AEDs: Broad-spectrum AEDs:
- phenytoin (Dilantin) - valproic acid (Depakote)
- phenobarbital - lamotrigine (Lamictal)
- carbamazepine (Tegretol) - topiramate (Topamax)
- oxcarbazepine (Trileptal) - zonisamide (Zonegran)
- gabapentin (Neurontin) - levetiracetam (Keppra)
- pregabalin (Lyrica) - clonazepam (Klonopin)
- lacosamide (Vimpat) - rufinamide (Banzel)
- vigabatrin (Sabril)
General Points
1. Brand vs. generic.
Every medicine has a brand and a generic name. The generic usually is cheaper, sometimes by quite a lot. For medicines introduced in recent years, patent (or “market exclusivity”) protection may block the sale of generic versions. A generic medicine usually works well, but it may not generate the same blood levels as does the brand name or an alternative generic medicine. Therefore, with changes of pill manufacturers, the blood levels can change. This may produce breakthrough seizures or side effects. The most important concern when taking generic drugs is to be sure the tablets are made by the same manufacturer for each refill. Switching from one generic manufacturer to another could result in different amount of active drug in each pill. The current author supports the right of the patient and doctor to know about medication substitution and consider whether generic substitution is safe.
2. Starting schedule
Many AEDs have to be started slowly to minimize side effects, event though this delays helping the seizures. The titration (starting) schedules are those of the author, and may be slower than is the schedule recommended in the package insert. Dosages are all for adults. Children are treated on the basis of their weight (mg per kg dosing basis).
3. Monotherapy
Some AEDs have approval for monotherapy (to be used alone) and others only as adjunctive (add-on) therapy to another AED. This reflects what testing evidence has been presented to the FDA - not all AEDs have gone through the required two clinical studies to show effectiveness in monotherapy. AEDs not proven effective in monotherapy still probably work well as single medications and are used that way by epilepsy doctors on a case-by-case basis where the benefit seems to exceed the risk.
4. Blood levels
Target blood levels are broad guides to clinical use. Actual blood levels differ for different laboratories. The desirable level depends upon the type and number of seizures, side effects, taking one vs. multiple drugs and other clinical factors.
5. Side effects
Side effects listed below are a brief compilation of the most common and most worrisome, not a full list. Every seizure medicine can sometimes cause side effects of fatigue, dizziness, unsteadiness, blurry vision, stomach upset, headaches, and reduced resistance to colds, memory and thinking problems. Weight gain tends to occur with valproic acid (Depakote), gabapentin (Neurontin), pregabalin (Lyrica) and carbamazepine (Tegretol, Carbatrol). Weight loss tends to occur with topiramate (Topamax), zonisamide (Zonegran) and felbamate (Felbatol). These are not mentioned separately in each section, unless they are especially common with the medicine. Detailed information is provided by the pharmacy as a package insert for new prescriptions and refills.
6. Effects on internal organs:
All seizure medicines can cause problems with blood counts (white cells, red cells and platelets), or liver or other internal organs, so doctors usually order blood tests to screen for these problems. Blood can be tested when starting a medicine to get a baseline, after a few months on the drug, every few months to yearly thereafter, then at individually determined times. The package insert often has recommendations, but there are no universal rules about when to test blood. All seizure medicines can produce either mild or severe allergic reactions. One, called the hypersensitivity syndrome, produces fever, rash, fluid accumulation, swollen lymph nodes, possible liver injury and confusion
7. Suicide warning
The US FDA has required a suicide warning on all seizure medications as a general class. All people taking them should be aware of and report any serious depression or suicidal thinking to their doctor, but the actual risk for suicide due to AEDs is quite low.
8. Mechanism
Mechanisms of action in the brain for antiepileptic drugs are described in simple form: most AEDs have multiple mechanisms of action to block seizures.
9. Not a cure
New Research-How the effectiveness of Antiepileptic Drugs in Adults Predict same result in Children?
Although AEDs are called “antiepileptic,” they do not cure epilepsy, but just suppress seizures while the medications are in the body.
In the September 5, 2012 journal Neurology published ahead of print, Dr. Pellock and colleagues from the Virginia Commonwealth University, Department of Epidemiology and Neurology, presented an important analysis on a common clinical issues that affects children throughout the world. It is well known that clinical trials are performed daily and the results are important for obtaining appropriate approvals for the use of new drugs in clinical practice. However, most clinical drug trials tend to exclude children and in fact, children are treated somewhat differently in that special trials have to be done specifically for this population. This often means that drugs and other therapies that are easily available for adults often take several years before they are officially approved for use in children.
The Details…
In the manuscript by Dr. Pellock and colleagues, the researchers looked at a meta-analysis (a combination of previously published studies in order to form new conclusions) and assessed how well antiepileptic drug trials that are performed in adults predict the effectiveness of that same drug in children. The investigators searched all medical literature from 1970 to January 2012 for clinical trials that addressed partial onset seizures and primary generalized tonic-clonic seizures in adults and in children. Independent epidemiologists used standardized search and study evaluation criteria to pick the trials that would meet the criteria for inclusion in this analysis.
The Results…
The investigators found that among 30 trials in adults and children, the effectiveness measures were consistent between adults and children for gabapentin, lamotrigine, levetiracetam, oxcarbazepine and topiramate.
Placebo controlled median percent seizure reduction between baseline and treatment groups were significant in 40 out of 46 groups, and 6 out of 6 of the treatment group studies. Responder rates (that is the percent of patients who have a 50% decrease in seizures) ranged from 2-43% in adults and from 3-26% in children and was significant for 37 out of 43 and 5 out of 8 treatment groups. However, in children less than 2 years of age, an insufficient number of trials were eligible and could not lead to adequate conclusions. The authors went on to conclude that the results of seizure trials that are performed in adults can be extrapolated to predict the effectiveness of those therapies in children.
Why is this important?
This study is an important one because as regulatory issues have increased precluding rapid implementation of therapies for both adults and children, children seem to be suffering the larger brunt of this particular problem. This study suggests that in many cases, what happens in adults will be very much predictive of the experience in children.
Despite this correlation, issues with regards to safety, development and school performance are specific to the pediatric population, and need to be addressed. Certainly in pediatric patients who are having difficulty with management of their seizures and are not responding to current therapy, the use of agents that are already approved for adults but are not approved in children seems to be a logical next step based on most of the work that has been done looking at recently approved seizure drugs.
(Source- journal Neurology)
