Children often have age-related syndromes, and may require medication only for a few years. Therefore, bone health and tera- togenicity are less of a concern in this population. Beha vioral and cognitive abnormalities in children with epilepsy may be caused either as a como rbidity of the underlying epilepsy syndrome or as a side effect of an AED ( 60 , 61 , 84 ); clinically disentangling these can be challenging. Therefore, there is particular attentio n to choose drugs that have as few adverse effects on cognition and behavior as possible ( 31 , 85 ). Choosing a medication available in liquid, sprinkle, or chewable formulations ma y also help with compliance. Adolescents, as they progress towards independence, may fail t o take medication, experiment with drugs and alcohol, or become sleep deprived when sociali zing or studying ( 86 , 87 ). There is a need to enable adolescents to be compliant without overly disrupt- ing their lives. Long acting formulations or an AED with a long half-life may help in this regard. Adolescents may have a low toler- ance for any adverse effects of a newly started medication, which can be partly mitigated with slow titration schedules and lower goal doses. Since sexual activity often begins in adolescence, ado- lescent females should be considered as women of childbearing age. Valproic acid should be avoided as \201 rst-line therapy in women with epilepsy when less potentially teratogenic options are availa- ble, and folic acid supplementation should accompany any AED choice ( 62 , 88 , 89 ). Comorbidities and concurrent medical problems A signi \201 cant proportion of individuals with epilepsy have comor- bid conditions, particularly the elderly and those with symptomat ic epilepsy. In these individuals, initial choice of medication must take into account pote ntial interactions with other medications as well as potential effects on the comorbidities themselves. Hepatic and renal impairment may affect clearance of medications, leading to h igher than expected blood levels. Many of the older AEDs are hepatic enzyme inducers (pheny toin, carbamazepine, phenobarbi- tal, oxcarbazepine) and may impact the ef \201 cacy of ot her medica- tions. Others, such as valproic acid, are strongly protein bound and may displa ce other medications, potentially causing acute toxicity. In addition, valproic acid inhibi ts the metabolism of other drugs, which may also cause toxicity. Zonisamide and topiramate increase the risk of renal calculi and should be used with cautio n in individuals predisposed to kidney stones. Carbamazepine and oxcarbazepine each may cau se hyponatraemia and should be used cautiously in patients with hyponatraemia from other ca uses. Weight gain (mild with car- bamazepine and gabapentin, moderate with valproic acid an d pre- gabalin) and loss (topiramate, zonisamide, felbamate) should be considered in overwe ight and underweight patients ( 97 , 98 ). The elderly may have more susceptibility to side effects, more medical comorbidities, polyp harmacy, and altered pharmacoki- netics and central nervous system pharmacodynamics ( 90 \200\22392 ). New-onset epilepsy in the elderly is almost always focal and often occurs in individuals with prior stroke or dementia ( 92 ). Preferred medications will have few drug \200\223drug interactions, little protein binding, minimal induction or inhibition of liver enzymes, and minimal cognitive side effects. Slow titration to lower goal doses may help r educe side effects. At present, trial data indicate that lamotrigine ( 90 , 93 ), gabapenti n ( 90 ), and an extended release for- mulation of carbamazepine ( 94 ) are effective and w ell tolerated in the elderly. Long-term AED therapy is associated with decreased bone health and fractures. Enzyme induci ng agents such as phenytoin, pheno- barbital, and primidone are most consistently implicate d, whereas the data are mixed on carbamazepine, oxcarbazepine, and valproic acid. Topiramat e and acetazolamide may lead to increased bone turnover via acidosis. Data on newer, non-en zyme-inducing drugs are limited but not exculpatory ( 99 ). Genetics Advances in epilepsy genetics have increased our understanding of the underlying p athophysiology and may eventually lead to tar- geted treatments. However, at present, speci \201 c genetic mutations Gender and implications for pregnancy Women with epilepsy require special attention to repr oductive and endocrine function. Unlike some other neurological disorders such as stroke or Parkinson \200\231s, which occur after the childbearing years, CHAPTER 22 management of patients with first seizure and early epilepsy 249 notify the Department for Transportation of their status ( 107 ). In the US and Canada, the length of driving prohibition and report- ing requirements vary by state or province. do not alter \201 rst-line therapy for newly diagnosed epilepsy. Instead, clinical phenot ype guides treatment. Even in the rare circumstances where a genetic diagnosis will lead to a speci \201 c AED, such as viga- batrin for infantile spasms in tuberous sclerosis ( 100 ), it is the clin- ical diagnosis (i.e. tuberous sclerosis) rather than the speci \201 c mutation that informs treatment. Prognosis Several factors help predict the prognosis for seizure control, including initial presentation (one seizure versus multiple sei- zures), etiology, number of seizures at ons et and in the \201 rst 6 months after diagnosis, response to initial AED, and epilepsy sy ndrome. Individuals who initially present with a single unpro- voked seizure have a greater than 90 % chance of remission at 5 years, irrespective of drug therapy ( 13 , 16 ). For ne wly diagnosed epilepsy, about half will respond to the \201 rst trial of monotherapy, and another 15 % will respond to a second trial of monotherapy or a two-drug combination ( 65 ). More than 80 % of patients with focal and generalized epilepsies may expect a 1-year rem ission within 5 years of diagnosis ( 74 , 108 ). Remote symptomatic etiology ( 61 , 109 \200\223111 ), failure to respond to the initial AED ( 61 , 109 \200\223111 ), and many sei zures at onset ( 65 ) or in the \201 rst 6 months after treat- ment ( 112 ) each suggest a poorer prognosis for remission. The \201 eld of pharmacogenomics, however, is rapidly assuming clinical importance by ide ntifying individuals at increased risk for dangerous side effects of AEDs ( 101 ). For exam ple, the HLA- B * 1502 allele places some East Asians, particularly Han Chinese, at higher risk for Stevens \200\223Johnson syndrome or toxic epidermal necrolysis when taking carbama zepine ( 102 ), and screening may reduce the risk ( 103 ). Similarly, the HLA-B * 3101 alle le may increase the risk in people of Northern European descent, though the risks are lower and the cost bene \201 t of this screening remains somewhat controversial ( 104 ). It is expected that within a decade, screening tools will identify additional genetic susceptibil ities to adverse events, and help guide clinicians on which medications to avoid in individ ual patients. This susceptibility information may eventually guide medication choice in new ly diagnosed epilepsy. Affordability All of the potential \201 rst-line medications discussed in this chapter ar e available generically, and are thus increasingly affordable to uninsured or underinsured patients. In patients with newly diag- nosed epilepsy, the controversial issue of brand ver sus generic is less important than in refractory patients or in those with prior adverse ev ents. In regions with limited resources for medical care, the older AEDs, such as phenobarb ital or phenytoin, are often sig- ni \201 cantly cheaper than newer medications. These dru gs provide similar ef \201 cacy, though a higher rate of adverse side effects, and may be considered when cost is an over-riding concern ( 105 , 106 ). Identifying the epilepsy syndrome greatly helps understand the prognosis. For example, the seizures in children with self-limited syndromes, such as benign rolandic epilepsy, will re mit with or without treatment; whereas fewer than 50 % of individuals with temporal lobe ep ilepsy will attain full remission ( 113 ). While there is clearly a need for better epileps y treatments, as well as improved early identi \201 cation of those with refractory epilep sy who may be candidates for more aggressive therapy, the majority of patients with early e pilepsy will attain seizure remission. References 1. Gowers WR . Epilepsy and Other Chronic Convulsive Diseases . London : J&A Churchill , New Burlington Street , 1881 . Counseling After a \201 rst seizure or the diagnosis of epilepsy, ideally after the resul ts of the initial EEG and neuroimaging are available, dedicate suf \201 cient time with th e patient (or family) to provide counseling and answer questions. Tailor the discussion to balance the need to convey critical advice with the ability of the patient (or family) to a bsorb the information. For patients starting medication, there are likely to be opportuniti es at future of \201 ce visits to reinforce coun- selling and raise additional issues not covered in the \201 rst encoun- ter. These patients have just recently been diagnosed and therefore need discussion of the issues common to all AEDs and seizure dis- orders as well as the speci \201 cs related to their particular diagnosis and treatment regimen. 2. Sander JW , Hart YM , Johnson AL , Shorvon SD . National General Practice Study of Epile psy: newly diagnosed epileptic seizures in a general population . 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