Repeated acute testing of anticonvulsant drugs in amygdala kindled rats: increase in anticonvulsant but decrease in adverse effect potential

PURPOSE: Because preparation of kindled rats is laborious, time-consuming, and expensive, such animals are often used for several experiments in the evaluation of anticonvulsant drugs (AEDs). Furthermore, for comparison with data on new drugs, often "historical" data on standard drugs obtained in previous experiments in other groups of kindled rats are used. Without knowing how factors such as repeated drug testing or seasonal variation in drug responses affect drug potencies in the kindling model, false conclusions and predictions might be drawn from such comparisons. In this study, we examined the anticonvulsant and adverse effects of the three clinically established AEDs carbamazepine (CBZ), phenobarbital (PB), and valproate (VPA) once per month in the same two groups of amygdala-kindled rats over a period of 9 (group 1) or 6 (group 2) consecutive months. To evaluate the possible effect of the season, experiments in group 1 were started in autumn, and experiments in group 2 in spring. METHODS: For quantification of anticonvulsant activity, the focal seizure threshold (threshold for afterdischarges; ADT) was determined after each acute drug treatment and compared with a control ADT determined 2-3 days before. RESULTS: The repeated acute (single-dose) drug testing in the same groups of amygdala-kindled rats led to three pronounced alterations in the animals: (a) a significant decrease in ADT, (b) a marked potentiation of AED effects on ADT, and (c) a striking reduction in ataxia produced by drug treatments. Drug levels in plasma, which were determined in each drug trial, showed only moderate variation over the period of the experiments, so that the observed alterations in drug responses were certainly not due to pharmacokinetic factors. PB and VPA, but not CBZ, showed a more potent anticonvulsant effect when experiments were started in October (group 1) compared with April (group 2), but this difference was rapidly overridden by the marked and progressive potentiation of anticonvulsant activity on repeated drug testing. CONCLUSIONS: These data demonstrate that repeated use of the same kindled rats for acute drug testing significantly alters the sensitivity of the animals to the anticonvulsant and adverse effects of drugs. Because the anticonvulsant potency increases, whereas the adverse effect potential decreases during repeated acute drug testing, this may lead to false-positive data on a test compound. The mechanisms involved in these observations deserve further studies.     

Comparison of Antiepileptic Drugs on Cognitive Function in Newly Diagnosed Epileptic Children: A Psychometric and Neurophysiological Study

Summary: Using a randomized parallel group study design, we compared the cognitive effects of carbamazepine (CBZ), phenobarbital (PB), and valproate (VPA) in children with epilepsy. Seventy-three children with newly diagnosed epilepsy were tested with the Wechsler Intelligence Scale for Children-Revised (WISC-R), Bender-Gestalt test, and auditory event-related potentials (P₃₀₀) before and 6 and 12 months after antiepileptic drug (AED) treatment. There were no significant differences in WISC-R IQs and Bender-Gestalt scores for children in any group at any of the three sessions. P₃₀₀ latencies were increased in the children receiving PB but not in children receiving CBZ and VPA. P₃₀₀ amplitudes were significantly reduced in treated children in all three groups, but amplitudes were not significantly different among the three groups. These findings suggest that PB may affect cognitive function of epileptic children and that the P₃₀₀ may be a sensitive additional procedure that can be used to assess the cognitive effect of AEDs.     

Renal tubular function in patients on long-term lithium therapy.

The authors conducted a study in which 10 patients with recurrent affective disorders who responded completely to long-term lithium therapy but who were otherwise unselected were tested for renal tubular concentrating and acidification ability. Despite frequent symptoms of thirst, polyuria, and nocturia, all patients were able to concentrate urine normally and all showed normal renal tubular acidification ability. A significant correlation was found between erythrocyte lithium concentration and maximum urinary osmolality.     

Thyroid function in girls with epilepsy with carbamazepine, oxcarbazepine, or valproate monotherapy and after withdrawal of medication

Summary: Purpose: Antiepileptic drugs may affect the serum thyroid hormone concentrations. The aim of this study was to evaluate thyroid function in 78 girls taking carbamazepine (CBZ), oxcarbazepine (OXC), or valproate (VPA) monotherapy for epilepsy and after withdrawal of the treatment. Methods: Forty‐one girls taking VPA, 19 taking CBZ, and 18 taking OXC for epilepsy, as well as 54 healthy age‐matched controls, aged 8 to 18 years, participated in the study. All the girls were examined clinically, and their pubertal stage was assessed. Blood samples were obtained for thyroid hormone and antibody assays. These examinations were repeated after a mean follow‐up of 5.8 years to assess thyroid function, and 64 (82%) of 78 patients and 42 (78%) of 54 controls agreed to participate in the second evaluation. Results: In the first evaluation, the mean serum thyroid hormone concentrations were lower in the girls taking CBZ [thyroxine (T₄), 70.2; SD, 10.9 nM; and free thyroxine (FT₄), 11.5; SD, 1.8 pM] or OXC (T₄, 74.9; SD, 16.4 nM; and FT₄, 11.3; SD, 1.8 pM) than in the control girls (T₄, 96.6; SD, 15.1 nM, and FT₄, 14.4; SD, 1.5 pM; p < 0.001, all comparisons). However, thyrotropin (TSH) concentrations were normal in the girls taking CBZ or OXC. Sixty‐three% of the girls taking CBZ and 67% of the girls taking OXC had serum T₄ and/or FT₄ levels below the lower limit of the reference range. The VPA‐treated girls with epilepsy had normal serum T₄ and FT₄ concentrations, but slightly increased TSH levels (3.3; SD, 1.5 mU/L; p < 0.01) compared with the control girls (2.5; SD, 1.0 mU/L). Normal serum hormone concentrations were restored in the patients who discontinued the medication. Conclusions: Both CBZ and OXC reduce serum thyroid hormone concentrations in girls with epilepsy. Conversely, VPA is associated with normal serum thyroid hormone and increased thyrotropin levels. However, our results suggest that the changes in serum thyroid hormone and thyrotropin levels are reversible after withdrawal of the medication.     

丙戊酸钠对成人癫痫患者认知功能的影响

目的了解丙戊酸钠对成人癫痫患者认知功能的影响。方法采用简易精神状态评定量表,分别于治疗前及治疗6个月、1年、2年、3年对74例接受丙戊酸钠治疗的成人癫痫患者认知功能进行评价,并选同期健康体检者85例作为对照组。结果癫痫组丙戊酸钠血药浓度均在正常浓度范围。简易精神状态评定量表评分：在干预前,癫痫组11项得分均低于对照组（P〈0.01）;在干预后6个月、1年、2年、3年,癫痫组11项得分均低于对照组（P〈0.05）;癫痫组自身与治疗前比较,11项得分均增高（P〈0.05）,但随时间延长无进一步改善趋势（P〉0.05）;癫痫组治疗前后原发性和继发性癫痫患者间比较无差异（P〉0.05）。结论成人癫痫患者存在认知功能下降,丙戊酸钠具有改善癫痫患者认知功能的作用。     

Thyroid function in men taking carbamazepine, oxcarbazepine, or valproate for epilepsy

PURPOSE: Antiepileptic drugs (AEDs) may affect serum thyroid hormone concentrations. This study aimed to evaluate thyroid function in men taking carbamazepine (CBZ), oxcarbazepine (OCBZ), or valproate (VPA) for epilepsy. METHODS: Ninety men with epilepsy (40 taking CBZ, 29 taking OCBZ, and 21 taking VPA monotherapy) and 25 control subjects participated in the study. After clinical examination, a blood sample for hormone, gamma-glutamyl-transferase (GGT) and antibody (ab) assays was obtained. RESULTS: Serum thyroxine (T4) and free thyroxine (FT4) concentrations were low in men taking CBZ or OCBZ. Forty-five percent of men taking CBZ and 24% of men taking OCBZ had serum T4 and/or FT4 levels below the reference range. However, no correlations were found between T4 or FT4 and GGT concentrations in men taking CBZ or OCBZ. Thirteen percent of men taking CBZ, 17% of men taking OCBZ, and 6% of control men had increased levels of thyroid peroxidase (TPO)-ab and/or thyroglobulin (TG)-ab, but these were not associated with altered serum thyroid hormone concentrations. Serum triiodothyronine and thyrotropin levels in men taking CBZ or OCBZ were normal. In men taking VPA, the concentrations of thyroid hormones, thyrotropin, and antithyroid ab were normal. CONCLUSIONS: Serum thyroid hormone concentrations are low in CBZ- or OCBZ-treated men. However, these low levels do not seem to be due to liver enzyme induction or activation of immunologic mechanisms. Therefore, interference with hypothalamic regulation of thyroid function by CBZ and OCBZ seems possible. VPA does not have any significant effects on thyroid function.     

Lamotrigine monotherapy compared with carbamazepine, phenytoin, or valproate monotherapy in patients with epilepsy

OBJECTIVE: This open-label study evaluated the efficacy and tolerability of lamotrigine monotherapy compared with monotherapy with conventional antiepileptic drugs in patients converting from previous monotherapy because of inadequate seizure control or unacceptable side effects. METHODS: This study was conducted in 26 neurology clinics and epilepsy centers throughout the United States. The study enrolled 115 patients with epilepsy converting from previous monotherapy because of inadequate seizure control or unacceptable side effects. Patients were randomized 1:1 to receive 24 weeks of lamotrigine monotherapy or monotherapy with a conventional antiepileptic drug (carbamazepine, phenytoin, or valproate based on physician's choice). Patients were converted during an 相似文献   

卡马西平 托吡酯与丙戊酸钠治疗脑炎继发癫痫的疗效分析

目的观察卡马西平、托吡酯与丙戊酸钠治疗脑炎继发癫痫的疗效。方法选取60例脑炎继发癫痫患者为研究对象,随机分为A、B、C 3组,每组20例,A组给予卡马西平治疗,B组给予丙戊酸钠治疗,C组给予托吡酯治疗。对3组疗效进行评价;对3组患者治疗期间不良反应的发生情况进行观察。结果 3组临床有效率分别为70%、70%和75%,差异无统计学有意义(P0.05),且3组各项疗效评价结果差异均无统计学意义(P0.05);3组治疗期间不良反应的发生率分别为55%、45%和15%,A组或B组不良反应发生率显著高于C组(P0.05),A组皮疹发生率显著高于B组与C组(P0.05)。结论卡马西平、丙戊酸钠、托吡酯治疗脑炎继发癫痫的疗效基本相当,但托吡酯的不良反应较少,有助于提高患者的依从性。     

Lithium: long-term effects on the kidney. I. Renal function in retrospect

46 patients treated with lithium for an average of 8 years participated in a functional-morphological follow-up study based on a 12-day hospitalization and involving a kidney biopsy. The functional part of the study showed that tubular function was markedly influenced, leading to increased urine volume (average 3 1/24 h) and a decreased renal concentration capacity in 85% of the patients. Glomerular function was generally not influenced, and only 10% of the patients had glomerular filtration rates below their age-corrected normal ranges. Both urine volume and glomerular filtration rates showed significant correlations with dosage schedule. Urine volume was lower and glomerular filtration rate higher on a one-dose schedule than when lithium was given in divided doses during the day. It is concluded that discontinuity in lithium treatment minimizes lithium effects on kidney function.     

拉莫三嗪与卡马西平对新诊断癫（疒间）患者认知功能及生活质量影响的对照研究

目的研究新型抗癫药物拉莫三嗪(LTG)和传统抗癫药物卡马西平(CBZ)对新诊断部分发作性癫患者认知功能和生活质量的影响。方法采用随机、对照的临床研究方法,将符合标准的50例癫患者进行一组神经心理学和癫患者生活质量量表31(QOLIE31),以及头颅CT/MR、脑电图等检查,之后随机分别给予CBZ和LTG治疗。12周后复查相同检查。结果CBZ组治疗后较治疗前:逻辑延迟记忆下降,数字符号减少,QOLIE31中综合QOL和总体健康水平得分增加((P<0.05或0.01)),但药物影响和认知功能得分均下降(P<0.01);LTG组治疗后较治疗前:A型、B型连线测验时间、stroop读色时间减少,逻辑记忆、逻辑延迟记忆、计算力以及数字符号增加(P<0.05或0.01),QOLIE31中情绪、总体健康水平、精力/疲乏、社会功能得分增加(P<0.05或0.01),药物影响得分下降(P<0.01),认知功能得分无显著性差异(P>0.05)。CBZ与LTG组治疗前后差值比较:LTG组A型连线时间减少(P<0.01),stroop读字正确数、逻辑延迟记忆、数字符号增加(P<0.05或0.01),LTG在药物影响和认知功能得分均优于CBZ组(P<0.01)。结论LTG在一定程度上可以改善新诊断部分发作性癫患者认知功能和生活质量。目的研究新型抗癫药物拉莫三嗪(LTG)和传统抗癫药物卡马西平(CBZ)对新诊断部分发作性癫患者认知功能和生活质量的影响。方法采用随机、对照的临床研究方法,将符合标准的50例癫患者进行一组神经心理学和癫患者生活质量量表31(QOLIE31),以及头颅CT/MR、脑电图等检查,之后随机分别给予CBZ和LTG治疗。12周后复查相同检查。结果CBZ组治疗后较治疗前:逻辑延迟记忆下降,数字符号减少,QOLIE31中综合QOL和总体健康水平得分增加((P<0.05或0.01)),但药物影响和认知功能得分均下降(P<0.01);LTG组治疗后较治疗前:A型、B型连线测验时间、stroop读色时间减少,逻辑记忆、逻辑延迟记忆、计算力以及数字符号增加(P<0.05或0.01),QOLIE31中情绪、总体健康水平、精力/疲乏、社会功能得分增加(P<0.05或0.01),药物影响得分下降(P<0.01),认知功能得分无显著性差异(P>0.05)。CBZ与LTG组治疗前后差值比较:LTG组A型连线时间减少(P<0.01),stroop读字正确数、逻辑延迟记忆、数字符号增加(P<0.05或0.01),LTG在药物影响和认知功能得分均优于CBZ组(P<0.01)。结论LTG在一定程度上可以改善新诊断部分发作性癫患者认知功能和生活质量。     

Influence of major antiepileptic drugs on attention, reaction time, and speed of information processing: results from a randomized, double-blind, placebo-controlled withdrawal study of seizure-free epilepsy patients receiving monotherapy

PURPOSE: All major antiepileptic drugs (AEDs) have been reported to be associated with cognitive side effects. Uncertainty exists regarding the degree of cognitive effects, primarily because many studies do not adhere to basic standards of methodology and design. The aim of this study was to assess the effect of discontinuation of AEDs in patients receiving monotherapy on measures of attention, reaction time, and speed of information processing. METHODS: The 150 subjects who had been seizure free>2 years on drug monotherapy went through a randomized, double-blind, placebo-controlled study. Each patient was included for 12 months or until seizure relapse. Cognitive function was assessed with the California Computerized Assessment Package at baseline and 7 months after discontinuation. RESULTS: The major finding in this study is that discontinuation of major AEDs significantly improved performance on tests that require complex cognitive processing under time pressure. The difference in speed of cognitive processing between the two groups on these tasks was between 24 to 43 ms. Simple tasks of attention and reaction time revealed no significant differences between the discontinuation group and the nondiscontinuation group. Most of the subjects in the study were medicated with carbamazepine (CBZ) and valproate (VPA). The outcome of discontinuation of CBZ was similar to the outcome for the total study population, whereas withdrawal of VPA revealed only a nonsignificant tendency in the same direction. CONCLUSIONS: The results suggest that seizure-free epilepsy patients receiving monotherapy can obtain improvement in cognitive function if they discontinue AED treatment.     

Oxcarbazepine long-term treatment retention in patients switched over from carbamazepine

Abstract We evaluated the long-term outcome of oxcarbazepine (OXC) monotherapy in a population of patients switched over from carbamazepine (CBZ) monotherapy. Subjects of the study were recruited among patients who had successfully completed the PRIMO study, a recent multicentre Italian study that assessed the therapeutic equivalence of immediate (overnight) and more progressive switching from CBZ to OXC monotherapy in patients with partial seizures unsatisfactorily maintained on CBZ monotherapy due to poor tolerability or scant clinical efficacy. Treatment retention rate was chosen as a composite parameter for both efficacy and tolerance of OXC. Twelve months after having completed the PRIMO study, 91 of 105 patients (87%) were still taking OXC, 80 of them (76%) as monotherapy. Mean OXC dose was 1250±459 mg/day. Eighty-four out of 105 patients (80%) rated OXC tolerability as “good” or “very good”. The mean ratio of the last dose of OXC to the last dose of CBZ increased from 1.54 (end of PRIMO study) to 1.69 (end of follow-up). The large majority of a population of patients who were successfully switched from CBZ monotherapy to OXC monotherapy maintained OXC treatment for at least a further 12 months. The 1.5 OXC/CBZ ratio appears to be close to the optimal for the switch from CBZ to OXC, at least in patients treated with CBZ monotherapy. *The Follow-up PRIMO study group comprised the following: L. Antonini, G. De Maria (Brescia), G. Avanzini (Milan), P. Basso, B. Bettini (Gallarate, Varese), P. Benna (Turin), A. Baruzzi, F. Bisulli (Bologna), D. Consoli (Vibo Valentia), P. D’Alessandro (Perugia), P. Garofalo (Vicenza), L. Murri (Pisa), G. Muscas (Firenze), S. Musumeci (Troina, Enna), A. Paggi (Ancona), B. Passarella (Brindisi), S. Striano (Napoli), C. Zucca (Bosisio Parini, Como).     

The frequency of reversible parkinsonism and cognitive decline associated with valproate treatment: a study of 364 patients with different types of epilepsy

PURPOSE: We report the frequency of parkinsonism and cognitive decline (P/CD) in patients treated with valproate (VPA) after 1 year of treatment and at least 1 year of follow-up. METHODS: Three hundred sixty-four patients with various epileptic syndromes and seizure types were treated with VPA mono- or polytherapy for more than 1 year. RESULTS: We found five cases of P/CD (1.37%; 95% CI, 0.18-2.56%). Among 140 patients with different adverse effects (AEs) of VPA, P/CD were among the rarest in frequency but significant in terms of drug discontinuation (five of 17). CONCLUSIONS: Early identification of this type of AE and discontinuation of the drug led to complete recovery in affected patients.     

Sodium valproate, hyperandrogenism and altered ovarian function in Indian women with epilepsy: a prospective study

PURPOSE: To assess the association of long-term sodium valproate therapy with reproductive endocrine disorders in Indian women with generalized epilepsy. METHODS: Clinical parameters, ovarian morphology, and serum reproductive hormone concentrations were evaluated in 30 clinically normal and eumenorrheic reproductive age women with generalized epilepsy who were newly initiated on valproate. Longitudinal evaluations were done in 25 of these women after 1 year, and in some of them after 2 and 3 years of therapy. RESULTS: Of the 25 women who completed 1 year follow-up, we observed clinically relevant weight gain in 40%, hirsutism in 20%, menstrual abnormalities in 24%, polycystic ovaries (PCO) in 16%, polycystic ovarian syndrome (PCOS) in 20%, and a significant increase in mean serum testosterone (p=0.046). A significant positive correlation existed between weight gain and the development of menstrual abnormalities (r=0.66, p<0.0001), hirsutism (r=0.53, p=0.006) and PCO (r=0.51, p=0.012). No correlation existed between weight change and serum reproductive hormonal changes. Yearly follow-up for next 2 years in some of these women revealed persistence of menstrual abnormalities, hirsutism and PCO, a significant linear increase in mean body weight, body mass index, and serum testosterone concentrations, and an increase in serum LH levels from second year onwards. LIMITATIONS: Limitations include small sample size and a high dropout rate on follow-up. CONCLUSIONS: Long-term valproate therapy in Indian women with generalized epilepsy is associated with development of hirsutism, significant weight gain, stable or progressive alterations in reproductive hormonal function, and ultimately a higher occurrence of PCOS.     

Increased bone turnover in prepubertal,pubertal, and postpubertal patients receiving carbamazepine

PURPOSE: To study the markers of bone turnover in epilepsy patients in the different stages of the pubertal growth before and after the beginning of carbamazepine (CBZ) monotherapy. METHODS: We have investigated bone turnover in 60 epilepsy patients treated with CBZ. They were stratified according to pubertal stage and compared with a control group of 60 sex- and age-matched healthy children. RESULTS: After 2 years of therapy, we found higher values of the serum markers of bone formation [bone alkaline phosphatase (bone ALP), osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP)], and of bone resorption [carboxy-terminal telopeptide of type I collagen (ICTP) and the urinary cross-linked N-telopeptides of type I collagen (NTX)] in patients than in control subjects, in presence of a normal vitamin D metabolism. CONCLUSIONS: CBZ induces an increase of bone formation and of bone resorption that seems to be independent of the pubertal stage.     

Effect of Aminophylline and Enprofylline on the Protective Efficacy of Common Antiepileptic Drugs Against Electroconvulsions in Mice

The anticonvulsant potency of phenobarbital (PB) (120 min before the test), phenytoin (PHT) (120 min), carbamazepine (CBZ) (60 min), valproate (VPA) (30 min), and acetazolamide (60 min) alone or in combination with either aminophylline (50 mg/kg, 30 min) or enprofylline (46.2 mg/kg, 30 min) was measured against maximal electroshock-induced convulsions in mice. All drugs were administered intraperitoneally (i.p.), and the protective efficacy of each drug was expressed as ED50 in milligrams per kilogram. Aminophylline decreased anticonvulsant activity of PB, PHT, CBZ, and VPA, increasing the respective ED50 values from 16 to 28 mg/kg, 7.4 to 14 mg/kg, 18 to 26 mg/kg, and 260 to 335 mg/kg. On the contrary, enprofylline in the equimolar dose did not exert such effect. Furthermore, neither aminophylline nor enprofylline affected anticonvulsant action of acetazolamide. The present data favor enprofylline as a preferable drug for treatment of obstructive lung diseases in epilepsy patients. However, accurate pharmacokinetic data in mice and men for both xanthines are necessary if one attempts to compare their cerebral and pulmonary actions.     

Osteomalacia in institutionalized epileptic patients on long-term anticonvulsant therapy

The occurrence of anticonvulsant osteomalacia was studied in 31 epileptic inpatients, 16 women and 15 men.
Disturbances in biochemical parameters indicating osteomalacia were frequent. Thirty two per cent of the patients were hypocalcemic, 55% had an increase in S-ALP and 26% in U-HOP, and dU-Ca was decreased in 55%. The S-25OHD₃ concentrations were significantly lower in the patients compared with healthy controls. BMD was decreased in females but not in males compared with the controls. Histomorphometric analysis revealed an increase in the amount of osteoid, but the amount of trabecular bone was no lower than in the controls. The amount of resorption surfases was increased in the females, but not in the males. The patients who took less physical activity had a pronounced decrease in BMD.
The conclusion drawn was that osteomalacia is a frequent complication of long-term anticonvulsant medication, especially among institutionalized patients.     

Cardiac function and antiepileptic drug treatment in the elderly: A comparison between lamotrigine and sustained-release carbamazepine

Purpose: To investigate the comparative effects of carbamazepine (CBZ) and lamotrigine (LTG) on electrocardiography (ECG) parameters in elderly patients with newly diagnosed epilepsy. Methods: The study was conducted in the Norwegian subcohort (n = 108) of an international randomized double‐blind 40‐week trial, which compared the efficacy and tolerability of LTG and sustained‐release CBZ in patients aged 65 and older with newly diagnosed epilepsy. Target maintenance doses were 400 mg/day for CBZ and 100 mg/day for LTG, with adjustments based on clinical response. Patients with significant unpaced atrioventricular (AV) conduction defect were excluded. Resting 12‐lead ECG recordings were made under standardized conditions at pretreatment (baseline) and at the 40‐week study visit (treatment visit). Changes in QRS interval (primary endpoint), heart rate (HR), PQ, and QTc (HR‐corrected QT) intervals were assessed and compared between groups. Results: Of the 108 patients randomized, 33 discontinued prematurely because of adverse events (n = 24, none of which was cardiac) or other reasons (n = 9), and 15 were nonevaluable due to incomplete ECG data. None of the assessed ECG parameters differed significantly between groups at baseline. No significant ECG changes were recorded between baseline and treatment visit for QRS duration and QTc intervals, whereas HR fell and PQ intervals increased slightly on both treatments. However, there were no differences between groups in changes from baseline to treatment visit. There were no significant relationships between individual ECG changes and serum drug concentrations, except for QTc intervals, which decreased slightly with increasing CBZ concentrations. The proportion of patients with ECG parameters outside the normal range at treatment visit was similar to that recorded at baseline. Discussion: Clinically significant ECG changes are not common during treatment with CBZ or LTG in elderly patients with no preexisting significant AV conduction defects.     

Long‐term outcome of phenobarbital treatment for epilepsy in rural China: A prospective cohort study

Purpose: To evaluate the long‐term outcome of phenobarbital treatment for convulsive epilepsy in rural China, and to explore factors associated with overall seizure outcomes. Methods: We carried out follow‐up assessments of people who took part in an epilepsy community management program conducted in rural counties of six provinces in China. People with convulsive epilepsy who were previously untreated (or on irregular treatment) were commenced on regular treatment with phenobarbital. Information was collected using a standardized questionnaire by face‐to‐face interviews of the individuals (and their families where necessary). Information collected included treatment status, medication change, seizure frequency, and mortality. Key Findings: Among the 2,455 people who participated in the original program, outcomes were successfully ascertained during the follow‐up assessment in 1986. Among them, 206 had died. Information on treatment response was obtained in 1,780 (56% male; mean age 33.9 years, range 3–84; mean duration of follow‐up 6.4 years). Among them, 939 (53%) were still taking phenobarbital. The most common reasons for stopping phenobarbital were seizure freedom or substantial seizure reduction, socioeconomic reasons, and personal preference. Four hundred fifty‐three individuals (25%) became seizure‐free for at least 1 year while taking phenobarbital, 88% of whom did so at daily doses of 120 mg or below. Four hundred six (23%) reported adverse events, which led to withdrawal of phenobarbital in <1%. The most common adverse effects were malaise/somnolence (7.4%), dizziness (3%), and lethargy (2.6%). At the follow‐up assessment, 688 (39%) individuals had been seizure free for at least the previous year. People with persistent seizures had significantly longer duration of epilepsy and higher number of seizures in the 12 months before treatment. People who were taking AED treatment irregularly at recruitment were less likely to become seizure‐free. Significance: We observed long‐term benefits of regular treatment with phenobarbital for convulsive epilepsy in rural China. One hundred years after the discovery of its antiepileptic effect, phenobarbital is still playing an important role in the management of epilepsy.