The Study Of Efficacy And Safety Of Combination Therapy Of Low-dose Of Valproic Acid And Lamotrigine For Newly Diagnosed Epilepsy

BackgroundEpilepsy is a common neurological disease. The prevalence rate is about5‰,and the annual incidence rate is (50-70)/100000. Currently, there are more than9million people with epilepsy in China.There are650,000-700,000new-onset epilepsyannually. Antiepileptic drugs have been always the first choice of treatment ofepilepsy. Most experts advocate for patients with newly diagnosed epilepsymonotherapy. Monotherapy is convenient and it’s good to improve the complianceand retention rate of patients. But only about60%of patients can be controlledcompletely in this way, more than40%patients need to change to anotherantiepileptic drug or in combination with another anti-epileptic drug. Some scholarsclaimed that patients with newly diagnosed epilepsy could be given combinationtherapy at first in1960s and1970s. Under the premise of not increasing adversereactions, it may be more significant effect than monotherapy because of synergy in pharmacological mechanism and interaction between the pharmacokinetic of drugs.Recent years, with the development of new antiepileptic drugs, their uniquemechanism, and less interaction between them, combination therapy becomes ahotspot once again. In addition, the efficacy of new antiepileptic drugs is similar totraditional antiepileptic drugs, but they have fewer side effects, and they are safer andgood at tolerability, so their retention rate of clinical applications is higher.Lamotrigine (LTG) is a new antiepileptic drug studied more recently, with theresearch of Lamotrigine pharmacokinetic deeply and the popularity of therapeuticdrug monitoring, more and more papers indicated that therapeutic effect ofantiepileptic of valproic acid combined with LTG was significant.Although VPA canreach therapeutic concentration quickly and control seizures timely, it can causeweight gain, metabolic syndrome, polycystic ovary syndrome, insulin resistance,teratogenic and other adverse reactions in long-term use with normal dose.Since VPAinhibits metabolism of LTG, increases blood levels of LTG, LTG dose should reducewhen they used in conjunction.Though LTG add-on VPA was effective to VPA invalid patients, so far there isno report of patients with newly diagnosed epilepsy treat by the two drugsconjunction, and both VPA and LTG common adverse reactions are dose-related, sowe chose the semi-regular lowest dose as the maintenance dose for patients withnewly diagnosed epilepsy to combination therapy, and observed the efficacy andadverse reactions.ObjectiveSurvey the clinical efficacy of low-dose combination therapy of VPA and LTG tonewly diagnosed epilepsy, and the adverse reactions. Analyze relevant datas toevaluate the efficacy and safety, to provide more effective and safe initial treatmentfor patients with newly diagnosed epilepsy.MethodsSelected60patients newly diagnosed epilepsy for their clinical manifestationsand/or electroencephalogram(EEG) from December2012to August2013inoutpatient of our hospital. Gave magnesium valproate sustained-release tablets,250mg bid for adults,10mg/(kg d) for children,1-2times daily. Increase the amount of Lamotrigine tablets gradually: the initial dose of adults was12.5mg/d,25mg/d two weeks later, the target dose was25mg bid at the fifth week; the initialdose of children was0.15mg/(kg d),0.3mg/(kg d) two weeks later, the target dosewas1mg/(kg d) at the fifth week. Added amount period were all four weeks. Recordtheir seizures, heights, weights, waist circumferences, hip circumferences, fastingglucose, fasting insulin, routine blood and liver function before treatment, at the fifthweekend, at the12th weekend, and at the24th weekend. Monitor plasmaconcentrations of VPA and LTG at the fifth weekend, the12th weekend, and the24thweekend. Inspect24hours long-range EEG for patients inrolled before treatment andat the24th weekend respectively.Use SPSS17.0to process the data.Results1. Full control rates were83.9%,86.0%,75.5%, and total efficiency was98.2%,94.0%,95.9%at the fifth weekend, the12th weekend, and the24th weekend.2. After treatment, BMI and waist hip rate (WHR) of patients enrolled hadincreased a little (P=0.002, P=0.012).3. Fasting glucose, fasting insulin and homeostasis model insulin resistanceindex (HOMA-IR) did not change significantly after treatment (P=0.331, P=0.236,P=0.175).4. Differences between different gender, age, disease duration, seizure frequency,or seizure type were not statistically.5. BMI increased mainly in patients less than18years old, female patients ormore than1year duration patients. Difference was statistically different.WHR ofpatients less than18years old increased statistically (P=0.001). Fasting glucose andfasting insulin declined in female patients (P=0.026，P=0.019).6.8cases epileptiform discharges disappeared after treatment among14patientsEEG with epileptiform discharges in49patients who completed24weeks follow-up.7. One suffered from liver function damage and blood abnormalities (turn toLTG monotherapy), two suffered from nausea or vomiting, two suffered fromdrowsiness，two suffered from fatigue,one suffered facial swelling, one suffered fromtremors. All of these appeared in the first five weeks.8cases of adverse reactions weremild and disappeared without special treatment. All patients appeared no rash. Conclusions1. Low-dose combination therapy of VPA and LTG to newly diagnosed epilepsyis significant effect and fast onset.2. Low-dose combination therapy of VPA and LTG to newly diagnosed epilepsyis safe, and it does not cause insulin resistance.3. Low-dose combination therapy of VPA and LTG to newly diagnosed epilepsymay increase BMI, but slightly compared with conventional VPA dose, mainly inWHR.