Interictal Autonomic Nervous System Function in Patients with Epilepsy

Summary: We studied 24 patients with partial seizures receiving carbamazepine (CBZ) monotherapy and 40 normal controls, 17 of whom were tested with and without CBZ therapy. Autonomic nervous system assessment included baseline heart rate (HR) and blood pressure (BP); BP and HR changes during orthostasis and cold pressor test (CPT); and HR changes during sinus arrhythmia, Valsalva maneuver, and cold face test with apnea (CFTA). Our study demonstrated normal interictal autonomic function in patients with epilepsy, but, variations in BP and HR during orthostasis and CPT were significantly (p CBZ. Epilepsy patients had higher initial increases in BP and greater subsequent decreases in BP than did nonmedicated controls during CPT. Controls with CBZ had higher HR during orthostasis and CFTA than did those without CBZ. CBZ levels correlated with baseline and orthostatic BP and HR during deep breathing (sinus arrhythmia). Our results showed that patients with epilepsy have greater BP and HR variability and reactivity than controls, attributable in part to CBZ levels.     

Levodopa, bromocriptine and selegiline modify cardiovascular responses in Parkinson's disease

Autonomic nervous system (ANS) involvement is frequently found in Parkinson's disease (PD), but its causal relationship to the disease itself and its medication is unclear. We evaluated the effects of PD medications on cardiovascular ANS functions. Heart rate (HR) responses to normal and deep breathing, the Valsalva manoeuvre and tilting, and blood pressure (BP) responses to tilting and isometric work were measured prospectively in 60 untreated PD patients randomised to receive either levodopa (n=20), bromocriptine (n=20) or selegiline (n=20) as their initial treatment. The results were compared with those of 28 healthy controls. The responses were recorded at baseline, after 6 months on medication and following a 6-week washout period. At baseline HR responses to normal breathing, deep breathing and tilting were already lower and the fall in the systolic BP immediately and at 5 min after tilting was more pronounced in the PD patients than in the controls. Six months' levodopa treatment diminished the systolic BP fall after tilting when compared to baseline, whereas bromocriptine and selegiline increased the fall in systolic BP after tilting and selegiline diminished the BP responses to isometric work. The BP responses returned to the baseline values during the washout period. The drugs induced no change in the HR responses. Thus PD itself causes autonomic dysfunction leading to abnormalities in HR and BP regulation and the PD medications seem to modify ANS responses further. Bromocriptine and selegiline, in contrast to levodopa, increase the orthostatic BP fall and supress the BP response to isometric exercise reflecting mainly impairment of the sympathetic regulation. Received: 17 February 2000 / Received in revised form: 25 May 2000 / Accepted: 15 June 2000     

Interictal cardiovascular autonomic responses in patients with temporal lobe epilepsy

PURPOSE: To measure interictal cardiovascular autonomic functions in patients with either refractory or well-controlled temporal lobe epilepsy (TLE). METHODS: For autonomic assessment, heart rate variation during normal and deep breathing, Valsalva maneuver, and tilting were measured in 19 patients with chronic refractory TLE, 19 patients with well-controlled TLE, and 38 age- and sex-matched healthy control subjects. Blood pressure responses to tilting and isometric work also were evaluated. RESULTS: Heart-rate (HR) variation during normal breathing (p = 0.006) and tilting (p = 0.043) was lower in patients with refractory TLE than in control subjects. Heart-rate response to tilting (p = 0.036) was also lower in patients with well-controlled TLE than in control subjects. Blood-pressure responses showed no differences between the patients and the control subjects. Patients taking carbamazepine (CBZ) medication had decreased HR responses to deep breathing (p = 0.046) and to tilting (p = 0.014) compared with the control subjects. CONCLUSIONS: Refractory TLE seems to be associated with dysfunction of the cardiovascular autonomic regulation, manifesting as impaired HR responses to certain stimuli. Interictal autonomic dysfunction is seen in patients with well-controlled TLE as well, but it may be more evident in patients with refractory epilepsy. CBZ medication may also be associated with altered autonomic cardiac control.     

Adverse effects of carbamazepine,phenytoin, valproate and lamotrigine monotherapy in epileptic adult Chinese patients

Objective

Antiepileptic drugs (AEDs) have been widely used in patients with epilepsy but the adverse effects in adult Chinese patients have not been investigated. This study evaluated the adverse effects of four commonly prescribed AED monotherapies with carbamazepine (CBZ), phenytoin (PHT), valproate (VPA), and lamotrigine (LTG) in adult Chinese patients with epilepsy.

Methods

The prospective open-label clinical trial was conducted at the Chongqing Epilepsy Center. The study enrolled 505 adults with newly diagnosed epilepsy, including generalized tonic–clonic (n = 110), partial and partial secondarily generalized (n = 395) seizures. Patients were evaluated by two clinicians at the Center and were prescribed one type of AED monotherapy with CBZ, PHT, VPA or LTG for a 24-month period. An adverse effect profile, as well as efficacy of monotherapy, was obtained through a face-to-face interview with the patient at each visit. A physical examination and routine laboratory tests were performed during a clinical screening.

Results

A total of 62.6% (316/505) patients successfully completed the AED monotherapy study: 64.3% of those receiving CBZ, 55.9%—PHT, 61.5%—VPA, and 66.2%—LTG. However, 34.7% of the patients discontinued the AED monotherapy because of unsatisfactory seizure control. Overall, 18% of patients experienced adverse effects: for CBZ (25/168; 14.9%), PHT (18/59; 30.5%), VPA (32/192; 16.7%) and LTG (16/86; 18.6%). The most common drug-related adverse events included gastrointestinal disturbances, loss of appetite and nausea, weight gain and fatigue/tiredness. Tremor and nystagmus occurred in some patients receiving PHT and VPA. Two CBZ, one PHT and four LTG patients (n = 7) discontinued the study due to rash.

Conclusion

Adult Chinese patients with epilepsy accepted and tolerated monotherapy with CBZ, PHT, VPA, and LTG. No fatal adverse events occurred. Unsatisfactory seizure control was a primary reason for withdrawal from the AED monotherapy study.     

Pregabalin drug interaction studies: lack of effect on the pharmacokinetics of carbamazepine, phenytoin, lamotrigine, and valproate in patients with partial epilepsy

PURPOSE: Pregabalin (PGB) is an alpha2-delta ligand with demonstrated efficacy in epilepsy, neuropathic pain, and anxiety disorders. PGB is highly efficacious as adjunctive therapy in patients with refractory partial seizures. METHODS: Given its efficacy as adjunctive therapy, the potential for interaction of PGB with other antiepileptic drugs (AEDs) was assessed in patients with partial epilepsy in open-label, multiple-dose studies. Patients received PGB, 600 mg/day (200 mg q8h) for 7 days, in combination with their individualized maintenance monotherapy with valproate (VPA), phenytoin (PHT), lamotrigine (LTG), or carbamazepine (CBZ). RESULTS: Trough steady-state concentrations of CBZ (and its epoxide metabolite), PHT, LTG, and VPA were unaffected by concomitant PGB administration. Likewise, PGB steady-state pharmacokinetic parameter values were similar among patients receiving CBZ, PHT, LTG, or VPA and, in general, were similar to those observed historically in healthy subjects receiving PGB alone. The PGB-AED combinations were generally well tolerated. PGB may be added to VPA, LTG, PHT, or CBZ therapy without concern for pharmacokinetic drug-drug interactions.     

Effects of long-term antiepileptic drug monotherapy on vascular risk factors and atherosclerosis

Purpose: Long‐term therapy with antiepileptic drugs (AEDs) has been associated with metabolic consequences that lead to an increase in risk of atherosclerosis in patients with epilepsy. We compared the long‐term effects of monotherapy using different categories of AEDs on markers of vascular risk and the atherosclerotic process. Methods: One hundred sixty adult patients who were receiving AED monotherapy, including two enzyme‐inducers (carbamazepine, CBZ; and phenytoin, PHT), an enzyme‐inhibitor (valproic acid, VPA), and a noninducer (lamotrigine, LTG) for more than 2 years, and 60 controls were enrolled in this study. All study participants received measurement of common carotid artery (CCA) intima media thickness (IMT) by B‐mode ultrasonography to assess the extent of atherosclerosis. Other measurements included body mass index, and serum lipid profile or levels of total homocysteine (tHcy), folate, uric acid, fasting blood sugar, high sensitivity C‐reactive protein (hs‐CRP), or thiobarbituric acid reactive substances (TBARS). Key Findings: Long‐term monotherapy with older‐generation AEDs, including CBZ, PHT, and VPA, caused significantly increased CCA IMT in patients with epilepsy. After adjustment for the confounding effects of age and gender, the CCA IMT was found to be positively correlated with the duration of AED therapy. Patients with epilepsy who were taking enzyme‐inducing AED monotherapy (CBZ, PHT) manifested disturbances of cholesterol, tHcy or folate metabolism, and elevation of the inflammation marker, hs‐CRP. On the other hand, patients on enzyme‐inhibiting AED monotherapy (VPA) exhibited an increase in the levels of uric acid and tHcy, and elevation of the oxidative marker, TBARS. However, no significant alterations in the markers of vascular risk or CCA IMT were observed in patients who received long‐term LTG monotherapy. Significance: Patients with epilepsy who were receiving long‐term monotherapy with CBZ, PHT, or VPA exhibited altered circulatory markers of vascular risk that may contribute to the acceleration of the atherosclerotic process, which is significantly associated the duration of AED monotherapy. This information offers a guide for the choice of drug in patients with epilepsy who require long‐term AED therapy, particularly in aged and high‐risk individuals.     

The effect of antiepileptic drug therapy on antioxidant enzyme activity and serum lipid peroxidation in young patients with epilepsy

Changes in antioxidant defense mechanisms and the resulting increased lipid peroxidation are involved in the pathogenesis of epilepsy. Research findings concerning the effect of antiepileptic therapies on these processes are discordant. The aim of our study was to estimate, firstly, the activity of the following antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GSSG-R), and secondly, malondialdehyde (MDA) serum concentration in children and adolescents newly diagnosed with epilepsy and receiving either carbamazepine (CBZ) or valproate (VPA) monotherapy, or polytherapy. The study group included 90 young patients with epilepsy, aged 6 months to 20 years. In 22 patients epilepsy was newly diagnosed; CBZ monotherapy was administered to 16 patients, VPA monotherapy--to 25, and polytherapy--in 27 cases. The control group consisted of 61 non-epileptic patients aged 4-17 years. SOD, GSH-Px and GSSG-R activities and MDA concentration were measured using spectrophotometry. SOD activity was decreased in newly diagnosed epileptic children receiving VPA or CBZ monotherapy (p < 0.05), or polytherapy (p < 0.01) in comparison to relevant levels in non-epileptic patients. GSH-Px activity was increased in all the patients, but significantly in those receiving polytherapy (p < 0.05). While in patients newly diagnosed with epilepsy no change in GSSG-R activity was found, its level was slightly lower both in those receiving VPA monotherapy and polytherapy, but increased in those with CBZ monotherapy. MDA concentration was elevated in all the epileptic patients, significantly (p < 0.05) both in VPA monotherapy and in polytherapy, while insignificantly--in newly diagnosed epilepsy and in CBZ monotherapy. Our results indicate that in the serum of children and adolescents with epilepsy the oxidants-antioxidants balance is modified by antiepileptic therapy.     

Antiepileptic Drug Therapy and Sexual Function in Men with Epilepsy

Summary: Purpose: To study the effects of antiepileptic drugs (AEDs) on sex hormone levels and sexual activity in a group of men attending a hospital-based epilepsy clinic. Methods: One hundred eighteen men being treated with AED therapy, 32 with epilepsy but not receiving AEDs, and 34 controls were recruited. All subjects were aged 18–65 years. Blood (20 ml) was removed for hormone assays, after which each subject completed a validated questionnaire [Sexuality Experience Scores (Frenken and Vennix, 1981)] aimed at exploring the individuals' sexual activity and attitudes to sexual morality. Results: Men taking carbamazepine (CBZ) only had significantly higher mean sex hormone-binding globulin (SHBG) levels than the control group. The CBZ group also had a significantly lower mean DHEAS concentration than the control, untreated, and sodium valproate (VPA) monotherapy groups. The phenytoin monotherapy group (PHT) had a significantly higher mean SHBG than both the control and untreated groups, and had a significantly higher mean total testosterone (TT) value than the control untreated, CBZ, and VPA groups, and a significantly lower mean DHEAS than the controls, untreated, and VPA groups. Men receiving more than one AED had significantly higher mean SHBG concentrations compared with control, untreated, and VPA groups. In addition, the poly-therapy group's mean TT was significantly higher than the control and VPA groups, although its mean DHEAS concentration was lower than the control, untreated, and VPA groups. There were no significant differences between the study groups in mean FT, Budrostenedione (AND), or estradiol levels. But the CBZ, PHT, and polytherapy groups had significantly lower mean free and rogen index (FAI) than the controls. The CBZ group had a lower mean FAI than the VPA group. The poly-therapy group had a lower FAI than the untreated group. Sexuality Experience Scores (SES) showed that those men receiving AEDs embraced a stricter sexual morality than the controls and untreated, and expressed greater satisfaction with their marriages than the control and untreated groups. Conclusions: Seizure type did not affect SES scores. Multiple regression showed men who had received further education were less accepting of strict sexual morality.     

Seizure freedom with different therapeutic regimens in intellectually disabled epileptic patients.

BACKGROUND: Epilepsy is a frequent condition in persons with intellectual disability and is more often difficult to treat than in the average population. Seizure freedom is the primary therapeutic goal which has important implications for the patient's quality of life. The aim of this study was to find out which antiepileptic therapy regimens (monotherapy or combination therapy) are effective in achieving this goal in intellectually disabled epilepsy patients. We were especially interested in the impact of the new antiepileptic drugs (AEDs) which were introduced during the past decade. METHOD: We investigated retrospectively the antiepileptic regimens on which the resident patients of a large epilepsy centre (as a rule with additional intellectual disabilities of different degrees) were seizure free in 2002. Information on antiepileptic medication and seizure frequency was taken out of the individual case documentation. It was also determined whether seizure free patients had already been seizure free in 1992. RESULTS: Two hundred and forty out of 675 patients (35,6%) with epilepsy were seizure free. The proportion of seizure freedom was 43,7% in patients with borderline intelligence, 39,2% in mild, 33,2% in moderate, 31,9% in severe, and 21,9% in profound intellectual disability. One hundred and twenty-two (50,8%) seizure free patients were on monotherapy; 53 of them were on CBZ (PB: 34, VPA: 25, PHT: 7, LTG: 3). Ninety-three patients (38,7%) were on duotherapies, CBZ/PB (27 patients), PB/PHT (17), and LTG/VPA (14) being the commonest. Of 18 (7,5%) triple therapies, LTG/PB/VPA (4 patients) was the commonest. Taken together, the five most frequent therapeutic regimens were CBZ monotherapy, PB monotherapy, CBZ/PB, VPA monotherapy and PB/PHT (a clear preponderance of classic AEDs). A distinction was made between "old seizure free" (seizure free already in 1992) and "new seizure free" (in 1992 still seizures) patients. In the 132 old seizure free patients the classic AEDs prevailed again, monotherapies with CBZ, PB and VPA being the most frequent regimens. In comparison, in the 78 new seizure free patients the novel combination LTG/VPA was the third most frequent, after the classic regimens CBZ/PB and CBZ; PB monotherapies were rare. CONCLUSION:In a majority of intellectually disabled patients with epilepsy (including those who became seizure free since 1992), complete seizure control has been achieved by monotherapy or duotherapy with classic AEDs. Of the new AEDs LTG in combination with VPA appears to be an important innovation.     

Treatment guidelines for adult epilepsy]

We reviewed the treatment strategies and choices of drugs for adult patients with epilepsy. As evidence from controlled studies for the older drugs is scarcely available from the literature, we added a clinical study performed in our hospital and an expert consensus study. Published randomized clinical studies revealed carbamazepine (CBZ) to be the treatment of choice, but provided little evidence for the differences in efficacy between phenytoin (PHT), valproate (VPA), phenobarbital (PB) and zonisamide (ZNS). The clinical study in our patients with intractable localization-related epilepsy indicated the superior efficacy of CBZ and PHT over VPA or ZNS. Sixty-nine experts converged on the opinion that monotherapy should be started with VPA for seizures of both idiopathic and symptomatic generalized epilepsy, and with CBZ for seizures of localization-related epilepsy. When the trials with 2-3 monotherapy failed, surgery should be considered for localization-related epilepsy. We proposed practical guidelines for treatment of patients with adult epilepsy, including rehabilitation and care for improvement of quality of life.     

Positive and Negative Psychotropic Effects of Lamotrigine in Patients with Epilepsy and Mental Retardation

Summary: Purpose: To describe significant positive or negative psychotropic effects of lamotrigine (LTG) observed in epilepsy patients with mental retardation (MR).
Methods: Seven mentally retarded epilepsy patients, [5 with Lennox-Gastaut syndrome (LGS)] who experienced significant behavioral improvements or worsening after addition of LTG to their medication regimen were studied.
Results: LTG produced behavioral improvements in 4 patients. Patient 1, a 14-year-old girl, had LTG added to valproate (VPA) and thioridazine, resulting in diminished lethargy, less hyperactivity, and more appropriate speech. In a 17-year-old boy (patient 2) LTG added to VPA, phenytoin (PHT), and gabapentin (GBP) lessened irritability and hyperactivity. In patient 3, a 41-year-old woman, LTG added to PHT, VPA, and carbamazepine (CBZ) diminished lethargy and enhanced her social interactions. In patient 4, a 27-year-old man, LTG monotherapy diminished irritability and hyperactivity. Adverse behavioral effects were noted in 3 patients. In patient 5, a 43- year-old man, LTG added to PHT, phenobarbital (PB), lorazepam, sertraline, and thioridazine produced irritability, hyperactivity, and poor cooperation. In patient 6, a 29-year-old woman, LTG added to VPA produced frequent screaming, temper tantrums, increased rocking movements, and hyperactivity. In patient 7, a 29-year-old man, LTG added to VPA and PHT resulted in severe exacerbation of baseline behaviors, including self-injurious activity, temper tantrums, and failure to obey simple instructions.
Conclusions: In some patients with epilepsy and MR, LTG has significant positive or negative effects on behavior.     

Outpatient sleep recording during antiepileptic drug monotherapy

The effects of sleep and sleep deprivation on epilepsy are well known, but the effects of seizures and antiepileptic drugs (AEDs) on sleep have been less well studied. We recorded nocturnal sleep in 17 patients receiving antiepileptic monotherapy with ambulatory cassette EEG devices. Twelve patients had complex partial seizures and five had tonic-clonic convulsions. Two patients' seizures were largely nocturnal, and no seizures occurred during sleep recording. Five patients each were taking phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA), and two were taking clonazepam (CZP), all with therapeutic serum levels and no toxic symptoms. Total sleep time was reduced, wakefulness increased, and sleep latency prolonged in partial seizures as compared with generalized epilepsy. REM sleep was reduced and its latency decreased in partial seizure patients. Both groups had decreased slow wave sleep; that of partial seizure patients was decreased more markedly. PHT increased sleep latency and decreased sleep time, and CBZ increased awakening and diminished slow wave and REM sleep. Patients taking VPA had slight reduction in slow wave sleep; those taking CPZ had decreased sleep and REM latencies. Epilepsy may affect nocturnal sleep, and the effects of partial and generalized seizure disorders may be different. AEDs may also have differential effects on nighttime sleep. These may prove important in the long-term management of epileptic patients.     

Cardiac autonomic dysfunctions in chronic refractory epilepsy

BACKGROUND: Sudden unexplained death is an important cause of mortality in patients with epilepsy and cause for this is not fully understood. One of the explanations is autonomic dysfunction (AD). Studies of AD in chronic refractory epilepsy are very few in the literature. AIM: To evaluate cardiovascular autonomic functions in chronic refractory epilepsy patients. METHODS AND MATERIALS: Seventy-three patients (31.5+/-9.8 years, M:F::45:28) with chronic intractable epilepsy attending the "refractory epilepsy clinic" at a tertiary referral center (National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, India) were enrolled. Age and gender matched healthy subjects were recruited as controls. Heart rate (HR) and blood pressure (BP) at rest and HR response after deep breathing, Valsalva maneuver, postural change and BP response to postural change and isometric work were recorded. AD was graded as early if one of HR or BP, definite if two or more HR and severe if two or more HR with BP based tests were detected to be abnormal. RESULTS: The mean age at onset and duration of epilepsy was 12.4+/-8.5 years and 19.02+/-9.07 years, respectively. Twenty-three (31.5%) patients of refractory epilepsy had early involvement while 25 patients (primary generalized: 8, partial: 17) had Definite AD, and 16 (primary generalized: 4, partial: 12) had severe autonomic dysfunction. ANCOVA results showed expiration-inspiration, standing maximum:minimum ratio, standing 2 min systolic and isometric diastolic BP of the dysfunction group significantly differ compared to the control group. Patients with longer duration of epilepsy (23.2 years) had more severe dysfunction (p < 0.05) than patients with relatively shorter duration (17.5 years) of epilepsy. Antiepileptic drugs (AED) used did not show any significant role on autonomic functions in this study. CONCLUSION: This is the first study from India to evaluate autonomic functions in refractory epilepsy patients. Autonomic dysfunction was noted in 56.3% of patients. Anticonvulsants used were not associated with AD. Longitudinal controlled studies with 'newly diagnosed' epilepsy patients will enhance further understanding about the role of autonomic system in epilepsy.     

Lack of an effect of valproate concentration on lamotrigine pharmacokinetics in developmentally disabled patients with epilepsy

PURPOSE: to describe the population pharmacokinetics of lamotrigine (LTG) in developmentally disabled (DD) patients with epilepsy and (2) to determine if there is an effect of valproate (VPA) concentration on the extent of the pharmacokinetic interaction between VPA and LTG. METHOD: a NONMEM population analysis of steady-state LTG serum concentrations was conducted in patients receiving LTG either as mono or polytherapy with either an enzyme inducer (IND)-carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB) or an inhibitor (VPA). RESULTS: sixty-two patients (33.6+/-11.3 years, 47+/-9.9 kg) receiving LTG monotherapy (n=19) or polytherapy with VPA (n=15), inducer(s) (n=32) or both (n=5) were evaluated. LTG dose of 369+/-236 mg per day (8.1+/-5.9 mg/kg per day) achieved LTG plasma concentrations of 6.8+/-3.3 microg/ml. The observed LTG monotherapy, LTG+IND, and LTG+VPA oral clearance (Cl/F) were 0. 69+/-0.2, 1.60+/-0.65 and 0.2+/-0.05 ml/kg per min, respectively. The final LTG Cl/F model was dependent on body weight, concomitant VPA, and either single or multiple inducers. Including the serum concentrations of CBZ, PHT, or VPA in the model, did not significantly improve estimates of Cl/F. CONCLUSION: LTG Cl/F in DD patients is similar to literature values for ambulatory adult patients; however, low weight adult patients have higher elimination rates, as well as an increased response to enzyme induction. VPA inhibition of LTG Cl/F is maximal within the usually accepted therapeutic range for VPA.     

Differential effects of antiepileptic drugs on neonatal outcomes

Offspring of women with epilepsy (WWE) on AEDs are at increased risks for major congenital malformations and reduced cognition. They may be at risk for other adverse neonatal outcomes. Women with epilepsy on carbamazepine (CBZ), lamotrigine (LTG), phenytoin (PHT), or valproate (VPA) monotherapy were enrolled in a prospective, observational, multicenter study of the neurodevelopmental effects of AEDs. The odds ratio for small for gestational age (SGA) was higher for VPA vs. PHT, VPA vs. LTG, and CBZ vs. PHT. Microcephaly rates were elevated to 12% for all newborns and at 12 months old, but normalized by age 24 months. Reduced Apgar scores occurred more frequently in the VPA and PHT groups at 1 min, but scores were near normal in all groups at 5 min. This study demonstrates increased risks for being born SGA in the VPA and CBZ groups, and transiently reduced Apgar scores in the VPA and PHT groups. Differential risks among the AEDs can help inform decisions about AED selection for women during childbearing years.     

Antiepileptic drug effects on somatosensory evoked potentials

Some evoked potential changes have been documented in chronic phenytoin (PHT), valproate (VPA), or benzodiazepine therapy, whereas other studies have suggested little change with carbamazepine (CBZ) or phenobarbital (PB). We recorded median and posterior tibial nerve somatosensory evoked potentials (SEPs) in complex partial seizure patients taking PHT, CBZ, or VPA in monotherapy with stable therapeutic serum levels and no toxic symptoms. Ten patients each were studied with PHT, CBZ, and VPA and were compared with age-matched controls. Median nerve responses were recorded at Erb's point, cervical spine, and contralateral cerebral sites; tibial nerve evoked potentials were recorded from popliteal fossa, lumbar, cervical spine, and midline scalp electrodes. Epileptic patients and controls did not differ in SEP latency, amplitude, or central condition time. PHT prolonged Erb's point and popliteal fossa latencies, but not central conduction time. CBZ had no effect on latencies or amplitudes. Evoked potential amplitudes were reduced by VPA, and cortical response latencies were minimally prolonged. Chronic antiepileptic therapy without toxicity had little effect on SEPs. PHT may have a slight effect on peripheral nerve conduction, and VPA may have an effect on amplitude of cerebral responses.     

Carbamazepine, Phenytoin, Sex Hormones, and Sexual Function in Men with Epilepsy

Summary We evaluated the effects of carbamazepine (CBZ) on serum androgen levels and sexual function prospectively for 5 years in 11 men with epilepsy and in 25 patients receiving either CBZ (14 patients) or phenytoin (PHT) (11) monotherapy for >5 years. Serum sex hormone binding globulin (SHBG) levels increased and free androgen index (FAI) decreased during CBZ treatment, and these changes correlated with duration of CBZ therapy. Similarly, serum SHBG levels increased and FA1 values decreased in patients receiving PHT for >5 years. CBZ and PHT increase serum SHBG levels, leading to decreased FAI. These drugrelated hormonal changes may be the primary cause of hyposexuality common in men with epilepsy.     

Clobazam Has Equivalent Efficacy to Carbamazepine and Phenytoin as Monotherapy for Childhood Epilepsy

Summary: Purpose: To compare the effectiveness of mono-therapy clobazam (CLB) to carbamazepine (CBZ) and phenytoin (PHT) in children with epilepsy.
Methods: Children aged 2–16 years with newly diagnosed epilepsy or previous failure of one drug (for poor efficacy or side effects) were assigned to one of two study arms and then randomized–CLB versus CBZ or CLB versus PHT. Eligible children had partial epilepsies or only generalized tonic-clonic seizures. After a drug initiation protocol, monotherapy treatment mimicked the usual routines used by Canadian child neurologists. Blinding used a "double dummy" technique with blinded medication serum levels (6–point scale). Intention to treat analysis using survival curves assessed the primary end-point–length of retention on the initial medication during the year after randomization.
Results: Fifteen centers entered 235 patients: 159 randomized to CLB versus CBZ and 76 to CLB versus PHT. Altogether, in all study arms, 119 received CLB, 78 CBZ, and 38 PHT. Overall, 56% continued to receive the original medication for l year with no difference between CLB and standard therapy (CBZ and PHT). Seizure control was equivalent for all three medications, as were side effects. PHT and CBZ induced more biologic side effects, such as rash, while CLB induced slightly more behavioral effects. Tolerance developed in 7.5% of patients receiving CLB, 4.2% with CBZ and 6.7% with PHT.
Conclusions: CLB should be considered as "first line" monotherapy along with CBZ and PHT for all partial and selected generalized childhood epilepsies.