a number of epidemiological studies carried out around the world have shown that the prevalence of epilepsy rises rapidly above this age , even increasing beyond the other prevalence peak which appears in infancy . on the one hand , we have those patients whose epilepsy started at whatever age and who are now over 60 year - old , and on the other hand those in whom it started after this age , the latter representing 25% of the new cases of epilepsy ( sander and shoevon 1996 ) .
the incidence of epilepsies in the over 60s is double the figure for those aged between 40 and 59 years old and follows a lineal growth reaching a figure of 140/100,000 for the over 80s , three times the figure for those in the 6069 year - old age group ( loiseau et al 1990 ; tallis et al 1991 ; hauser 1992 ; hauser et al 1993 ) .
thus , epilepsy together with cerebrovascular pathology and dementias is one of the most common neurological pathologies in old age . moreover , as will be seen below , both cerebrovascular pathology and dementias may be a cause of epilepsy . given the tendency towards an ageing population in the west , an increase in the number of epileptic patients , particularly in this segment of the population , can be expected . in spite of
the fact that more and more often , the epileptic patients encountered in the surgery are over 60 years old , this age group is rarely represented in the clinical trials which have led to the approval of the different antiepileptic drugs ( aeds ) .
the high co - morbidity , the frequency of polypharmacy , the increased risk of secondary effects and of mortality due to intercurrent causes in these patients are , among others , the reasons for their almost systematic exclusion from clinical trials . therefore , given the lack of evidence based on clinical trials , we shall try to determine the most appropriate antiepileptic drugs for these patients according to the characteristics of their epilepsy , the modifications in the metabolic capacity of the drugs which arise with age , the possibility of secondary effects of special relevance to the elderly and the characteristics of the different drugs .
in elderly patients , the critical phenomenology presents peculiarities which may make diagnosis more difficult .
for example , automatisms and auras are unusual in the elderly and often the crises present themselves as episodes of confusion or syncopal events . therefore ,
in almost half of the elderly patients who are finally diagnosed with epilepsy , epilepsy is not the initial suspected diagnosis ( ramsay et al 2004 ) .
furthermore , the appearance of an epileptic status as a form of presentation of the epilepsy is also more common among the elderly ( pryor et al 2002 ) .
it should be remembered that the elderly are more at risk of presenting reactive crises .
the metabolic disorders which may provoke a crisis , including hypo- or hyperglycemia , uremia , hyponatremia or hypocalcaemia , are more common among the elderly .
in addition , this section of the population tends to use drugs more frequently , including drugs potentially capable of inducing an epileptic crisis , as are some antidepressants , neuroleptics and certain antibiotics .
however , this increase in the incident rate only corresponds to certain types of epilepsy .
almost no idiopathic epilepsies start in this age group . in any case , we may encounter patients with idiopathic epilepsies which started at much earlier ages and who have reached old age . therefore , the possibility of a generalized epilepsy commencing in old age is remote , and given an patient aged over 60 who has developed epilepsy we should consider a focal epilepsy even when there is no clear focal start to the crises ( hiyoshi and yagi 2000 ) .
practically two thirds of epilepsies which develop at this age are symptomatic , and the other third are cryptogenic .
the most common cause of epilepsy among the over 60s is the cerebral - vascular pathology , related to almost 50% of epilepsies among the elderly ( asconape and penry 1991 ) .
moreover , epilepsy may be the first sign of an underlying vascular pathology which has not yet surfaced .
thus , the risk of epilepsy in hypertensive patients is five times higher than in those who are not hypertensive , probably in relation to a pathology of small blood vessels causing irritating symptoms before provoking an ictus ( ng et al 1993 ) .
cleary et al monitored a cohort of 4,709 patients with cryptogenic epilepsy which started at over 60 years old , and found that the relative risk of suffering an ictus in these patients compared with controls from the same population was 2.89 , suggesting that in many of these patients there was an alteration to the cerebral blood flow which manifested itself first as an epilepsy and then as an ictus ( cleary et al 2004 ) .
other frequently related causes of epilepsy in the elderly are brain tumors , cranial trauma and dementia .
the fact that we encounter symptomatic epilepsies conditions the therapeutic attitude , as the risk of recurrence is very high ( bergey 2004 ) , over 90% , and therefore starting treatment after the first crisis can be considered . in the majority of cases , good control of these epilepsies can be expected , but treatment will be indefinite , and the suspension of treatment even after several years without a crisis can not be considered , as recurrence is almost certain .
however this should be assessed for each particular case , as it will largely depend upon the risks that the patient and the doctor are willing to assume ( serrano castro , ramos lizana et al 2005 ) .
the physiology of elderly patients presents alterations which modify the pharmacokinetics of aeds , making patients more susceptible to secondary effects .
firstly , there is an atrophy of the gastric mucosa and a reduction in the intestinal motility , which may modify the absorption of aeds making it irregular .
in addition , there is a reduction in total body water , leading to a modification of the volume of distribution of the drugs and their half life , which may on occasions have significant consequences .
thus , the half life of diazepam goes from 20 hours in young people to 80 hours in those individuals aged over 80 , with the resulting risk of a build - up of the drug .
the free fraction of drugs which bond well to proteins , such as valproic acid , phenitoin or tiagabine may increase by as much as 60% , bringing with this the risk of secondary effects due to intoxication ( serrano castro , casado - chocan et al 2005 ) . finally , the capacity to eliminate drugs is also lower in the elderly than in young people .
the hepatic metabolism is much slower , which may lead to a build - up of drugs with intense hepatic metabolism , such as carbamazepine , phenitoin or lamotrigine .
moreover , these patients will have a higher sensitivity to phenomenons of hepatic induction or inhibition , given that their hepatic reserve is reduced . in addition , glomerular filtration is also reduced , which must be remembered when prescribing renally eliminated drugs such as levetiracetam , gabapentin or pregabalin .
an added problem is that the elderly often take multiple medications , increasing the risk of interactions and the possibility of secondary effects . in this respect ,
the lower the bonding to proteins and the lower the hepatic metabolism of a drug , the easier it will be to use and the lower the risk of interaction with other possible concomitant drugs .
in general , elderly patients are more sensitive to the secondary effects of drugs , even at reduced doses . in addition , certain secondary effects frequently related to aeds are of special relevance to the elderly . due to the inhibiting action on the central nervous system , many aeds may cause cognitive disturbances .
elderly patients often present a reduction in their cerebral reserve capacity , making them particularly sensitive to this secondary effect .
the possibility of inducing cognitive disturbances is very high with drugs such as phenobarbital , primadone , or the benzodiazepines , and is more moderate with phenitoin and topiramate .
drugs less frequently causing cognitive disturbances , and which are therefore safer for use by this segment of the population include oxcarbazepine , levetiracetam , gabapentin and lamotrigine .
osteoporosis is a common disorder among the over 60s , particularly among women , and may be the cause of significant disability due to chronic pain and a predisposition to fractures .
various aeds may induce osteoporosis , emphasizing a risk which is already high merely as a result of ageing .
some , such as phenobarbital , phenitoin or carbamazepine , do so by interfering with the metabolism as vitamin d. valproate can also induce osteoporosis by activating the osteoblasts which destroy bone tissue .
the risk of complications due to osteoporosis is multiplied in an elderly patient if we add in an aed capable of inducing osteoporosis .
therefore , the risk of hip fractures in women over 65 is doubled when taking one of these drugs ( ensrud et al 2004 ) . as such , a priori , we should avoid the use of osteoporosis inducing drugs in this segment of the population .
the possibility of various aeds causing an increase in weight is well known . in general , we tend to consider this secondary effect when treating young patients , especially women , based on the assumption that these patients may be most concerned about their figure
. however , it is extremely important to consider the possibility of causing an increase in weight in elderly patients , not for aesthetic reasons but for reasons of health .
an increase in weight increases the risk of type ii diabetes , cardiovascular mortality and osteoarticular problems in a population where the risk is already higher .
moreover , an increase in weight leads to clumsiness in a population which tends to be clumsy , and increases the risk of falls in a population with an increased risk of osteoporosis , and therefore , greater risk of fractures .
the adfs most frequently associated to weight increase include valproate ( more than half the patients ) , carbamazepine ( approximately a quarter of patients ) , gabapentin ( 15%20% ) and pregabalin ( 14% ) ( de toledo et al 1997 ; easter et al 1997 ; biton 2003 ; arroyo et al 2004 ) .
topiramate may induce weight loss , which can be useful for overweight patients , but in other cases this effect may also be harmful and lead to malnutrition ( ben - menachem et al 2003 ) .
therefore , the most recommended drugs for this segment of the population are those which do not tend to modify weight , including lamotrigine , levetiracetam and oxcarbazepine ( devinsky et al 2000 ; gidal , sheth , magnus et al 2003 ) .
from the above , we can deduce that we are faced with a population which will frequently present symptomatic focal epilepsies , for which a good response to medical treatment can be expected , even at lower dosages ( kwan and brodie 2001 ) .
the majority of aeds available have demonstrated a similar efficacy for treating this type of crisis ( mattson et al 1985 , 1992 ; brodie et al 1999 , 2002 ) .
therefore , the choice of drug will fundamentally depend upon its pharmacokinetic profile and the likelihood of causing secondary effects ( snchez - alvarez et al 2005 ) which , as we have seen , have particular repercussions among the elderly .
phenobarbital is a powerful antiepileptic , but its significant cognitive effects , the possibility of inducing osteoporosis and possible pharmacological interactions rule it out for the treatment of epilepsies developing for the first time among this group of patients .
phenytoin is probably the most widely used drug among the elderly due to the possibility of a rapid titration and intravenous administration .
however , the complexity of its pharmacokinetics , the possibility of interaction with other drugs , of inducing osteoporosis and its cognitive effects make it unadvisable ( birnbaum et al 2003 ) .
valproic acid is an antiepileptic with a broad spectrum , being very efficient for both focal and generalized epilepsies , although we are principally concerned with the former among this population .
it can be administered intravenously , enabling rapid titration , the treatment of status epileptics and can be prescribed without problem where the patient is required to follow a strict diet due to an intercurrent disease .
the pharmacokinetics present certain problems , including its high bonding to proteins and its capacity for hepatic inhibition , which may provoke pharmacological interactions .
but the main problem lies in the frequency with which it causes weight gain , which , as we have seen , is of particular significance to health among these patients .
other secondary effects of significance among elderly patients include osteoporosis and tremor , and even parkinson s , in a population particularly exposed to suffering from osteoporosis and tremors or parkinson s due to their age .
its main disadvantage is its hepatic capacity , making the risk of interaction with other drugs high , of particular significance in a population where polypharmacy is common .
another two side effects to consider due to their higher frequency among the elderly are hyponatremia and alterations to the heart conduction system , which may cause confused or syncopal episodes respectively .
the problems presented by carbamazepine have largely been resolved with oxcarbazepine , whose capacity for hepatic induction and alterations to the heart conduction system are lower than its predecessor .
however , it induces hyponatremia more frequently than carbamazepine does ( kutluay et al 2003 ) .
topiramate is a powerful antiepileptic but the frequency with which it causes cognitive disorders , especially naming defects makes it unadvisable as a first choice for this population .
other secondary effects to consider given their possible gravity , although uncommon , include renal lithiasis and metabolic acidosis .
finally , the frequency of secondary effects requires a very slow titration of the drug , implying a long lapse in time until the patient is protected ( reife et al 2000 ) .
lamotrigine is a powerful antiepileptic without cognitive effects , with linear kinetics , making it highly suitable for this population . from a pharmacokinetics perspective
, the main disadvantage is its hepatic metabolism , which may be induced by other drugs , with a significant reduction in plasmatic levels ( anderson et al 2002 ) . on the contrary
, valproic acid significantly raises its levels and may double its half life ( gidal , sheth , parnell et al 2003 ) .
moreover , the possibility of serious allergic reactions makes very slow titration necessary , taking several weeks for an efficient dose to be reached .
this time period is usually lower among elderly patients , as , in general , lower doses are required to control their epilepsy .
tiagabine is a gaba - ergic drug with little antiepileptic power , requiring administration in three doses , and which often induces significant somnolence , and therefore it is not recommendable for this population .
gabapentin has a most favorable pharmacokinetical profile , but its low antiepileptic activity makes it unadvisable .
its successor , pregabalin , has the same pharmacokinetic profile , with the advantage that its antiepileptic power is similar to that of other greater aeds ( gil - nagel and gomez alonso 2005 ) .
the main disadvantages are its capacity to induce somnolence and weight gain ( french et al 2003 ; brodie 2004 ) .
finally , levetiracetam is a powerful antiepileptic with a highly favorable pharmacokinetic profile , as it does not bond with proteins , nor does it metabolize in the liver and neither induces nor is induced .
it titrates rapidly , and therefore from the start of treatment the patient has an efficient dosage . the only disadvantage is its possibility of provoking slight irritability or psychiatric alterations in under 7% of elderly patients , usually in patients with prior psychomotor retardation ( ferrendelli et al 2003 ; morrell et al 2003 ; white et al 2003 ) .
table 1 summarizes the main advantages and disadvantages of each of the aeds . in view of these characteristics
, we could say that , for a similar a priori efficacy , the drugs with the most favorable pharmacokinetic profile are levetiracetam and pregabalin , followed by oxcarbazepine and lamotrigine , whose hepatic metabolism and bonding to proteins slightly increases the risk of drug interactions .
moreover , these drugs have few cognitive effects , do not cause osteoporosis and , except for pregabalin , do not affect bodyweight , making them particularly attractive for treating epilepsies in the elderly .
these patients usually have partial symptomatic crises , which tend to reoccur , but which respond well to antiepileptic treatment . given that a priori the efficacy of all the major aeds is similar in the treatment of partial symptomatic crises , the choice of aed for use in this population will depend upon the pharmacokinetic properties and side effects . in this respect ,
the aeds with a more favorable profile for starting antiepileptic treatment in elderly patients include levetiracetam , pregabalin , lamotrigine and oxcarbazepine .
 epilepsy among the elderly is a frequently occurring pathology , differing in etiology , clinical presentation and prognosis from those of young people . in addition , beyond a certain age , physiological modifications are produced in the metabolism which alter the pharmacokinetics of antiepileptic drugs ( aeds ) , increasing the risk of pharmacological interactions , already greater in these patients due to the frequency of polypharmacy . 
 furthermore , elderly patients are particularly sensitive to certain secondary effects of aeds , as for example , cognitive disturbances , osteoporosis or weight increase . given that the efficacy of the major aeds is a priori quite similar , and that the epilepsies occurring in this age - group generally have a good prognosis , the selection of an aed will depend more upon its pharmacokinetics and ability to induce certain secondary effects than on its efficacy . in this respect , 
 levetiracetam and pregabalin , followed by oxcarbazepine and lamotrigine have the most favorable pharmocokinetical profile . 
 moreover , on the whole these drugs have very few cognitive effects , do not induce osteoporosis and , with the exception of pregabalin , do not affect weight , making them the first selection for use in the treatment of epilepsy in the elderly . 
Introduction
Characteristics of epilepsy in the elderly
Modifications of the metabolism in the elderly
Secondary effects of special relevance in the elderly
First choice AEDs for the elderly
Conclusions