Barbiturate-refractory epilepsy: safe schedule for therapeutic substitution

Barbiturates are considered first line antiepileptic drugs in third world countries due to traditional and economic reasons. This prospective uncontrolled study of 52 patients aged 15 to 64 years (mean 24) demonstrates that patients who become refractory to barbiturates are mainly those with partial seizures with or without generalization or with a focal EEG abnormality (71%). Seizures tend to become refractory approximately 6 years after barbiturates were started. Progressive barbiturate withdrawal over a period of two to 8 months (mean 5) with institution of treatment with carbamazepine, phenytoin or sodium valproate allowed complete barbiturate withdrawal in 42 of the 52 patients (81%). Furthermore monthly seizure frequency in those in whom barbiturates were withdrawn decreased from 7.1 to 1.7 per patient. An improvement in mental status was observed but not measured. These results show that barbiturates should not be first-choice drugs in patients who have a chronic disease such as epilepsy, and indicate a schedule for barbiturate withdrawal Which is safe and independent of hospitalization or monitoring of antiepileptic drug serum concentrations.

Download Full-text

First, do no harm: the risks of overtreating children with epilepsy

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2007000100002 ◽

2007 ◽

Vol 65 (1) ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Eunice Chuang ◽

Marilisa M. Guerreiro ◽

Sara Y. Tsuchie ◽

Angelica Santucci ◽

Carlos A. M. Guerreiro ◽

...

Keyword(s):

Adverse Events ◽

Prospective Study ◽

Antiepileptic Drug ◽

Antiepileptic Drugs ◽

Seizure Frequency ◽

Seizure Control ◽

Control Method ◽

Refractory Epilepsy ◽

Do No Harm ◽

A Prospective Study

BACKGROUND: Although overtreatment with antiepileptic drugs contributes to the morbidity associated with epilepsy, many children still are overtreated. OBJECTIVE: To evaluate if the withdrawal of at least one antiepileptic drug (AED) in children with refractory epilepsy using polytherapy enable a better seizure control. METHOD: This was a prospective study. Children with refractory epilepsy using at least two AEDs were included. Once the patient, or guardian, agreed to participate in the study, one or more AED were slowly tapered off. The remaining AEDs dosages could be adjusted as needed, but a new AED could not be introduced. RESULTS: Fifteen patients were evaluated, three girls; ages ranging from 3 to 18 (mean=8.7 years). After at least one AED withdrawal, two (13.5%) patients became seizure free, seizures improved >50% in 5 (33.5%) patients, did not change in 5 (33.5%), and seizure frequency became worse in 3 (20%). Adverse events improved in 12 patients (80%). CONCLUSION: The withdrawal of at least one AED is a valuable option in the treatment of selected children with refractory epilepsy.

Download Full-text

Potassium currents in rat cortical neurons in culture are enhanced by the antiepileptic drug carbamazepine

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y90-079 ◽

1990 ◽

Vol 68 (4) ◽

pp. 545-547 ◽

Cited By ~ 43

Author(s):

C. Zona ◽

V. Tancredi ◽

E. Palma ◽

G. C. Pirrone ◽

M. Avoli

Keyword(s):

Antiepileptic Drug ◽

Antiepileptic Drugs ◽

Cortical Neurons ◽

Potassium Currents ◽

Patch Clamping ◽

Partial Seizures ◽

Complex Partial Seizures ◽

Voltage Dependent ◽

Rat Neocortex ◽

Rat Cortical Neurons

We report that carbamazepine (Tegretol), a drug that is useful for the treatment of complex partial seizures, enhances outward, voltage-dependent K+ currents generated by rat neocortical cells in culture and recorded with patch-clamping techniques. This effect is seen in the presence of therapeutic concentrations of carbamazepine (10–20 μM). Furthermore, at these doses carbamazepine does not influence voltage-dependent inward Na+ and Ca2+ currents recorded in these cells. The action exerted by carbamazepine on K+ currents is a novel finding and might represent an important mechanism for controlling neocortical excitability and thus the generation of epileptiform activity.Key words: potassium currents, antiepileptic drugs, carbamazepine, rat neocortex.

Download Full-text

▾ Lamotrigine – an add-on antiepileptic

Drug and Therapeutics Bulletin ◽

10.1136/dtb.30.19.75 ◽

1992 ◽

Vol 30 (19) ◽

pp. 75-76

Keyword(s):

Quality Of Life ◽

Side Effects ◽

Antiepileptic Drug ◽

Partial Seizures ◽

First Line ◽

Low Level ◽

Clonic Seizures ◽

Clinically Significant ◽

The Brain

Lamotrigine (Lamictal – Wellcome) is a new antiepileptic drug. It is licensed as ‘add-on’ treatment for patients with partial seizures, either localised to one part of the brain or spreading to tonic-clonic seizures (secondarily generalised), who are not satisfactorily controlled with first-line drugs. The manufacturer claims that it “offers the hope of an improved quality of life” while having “a low level of clinically significant side-effects”. We examine these claims.

Download Full-text

Effect of Neuroinflammation on ABC Transporters: Possible Contribution to Refractory Epilepsy

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527317666180828121820 ◽

2018 ◽

Vol 17 (10) ◽

pp. 728-735 ◽

Cited By ~ 6

Author(s):

Xiaolin Deng ◽

Yangmei Xie ◽

Yinghui Chen

Keyword(s):

Antiepileptic Drugs ◽

Abc Transporters ◽

Refractory Epilepsy ◽

Vascular Endothelial Cells ◽

Efflux Transporters ◽

Vascular Endothelial ◽

Intracellular Signalling Pathways ◽

The Brain ◽

Transporter Expression

Background & Objective: Epilepsy is a common and serious chronic neurological disorder that is mainly treated with antiepileptic drugs. Although current antiepileptic drugs used in clinical practice have advanced to the third generation, approximately one-third of patients are refractory to these treatments. More efficacious treatments for refractory epilepsy are therefore needed. A better understanding of the mechanism underlying refractory epilepsy is likely to facilitate the development of a more effective therapy. The abnormal expression and/or dysfunction of efflux transporters, particularly ABC transporters, might contribute to certain cases of refractory epilepsy. Inflammation in the brain has recently been shown to regulate the expression and/or function of ABC transporters in the cerebral vascular endothelial cells and glia of the blood-brain barrier by activating intracellular signalling pathways. Conclusion: Therefore, in this review, we will briefly summarize recent research advances regarding the possible role of neuroinflammation in regulating ABC transporter expression in epilepsy.

Download Full-text

Current and Emerging Pharmacotherapeutic Options for Smoking Cessation

Substance Abuse Research and Treatment ◽

10.4137/sart.s8108 ◽

2013 ◽

Vol 7 ◽

pp. SART.S8108 ◽

Cited By ~ 1

Author(s):

Kristin V. Carson ◽

Malcolm P. Brinn ◽

Thomas A. Robertson ◽

Rachada To-A-Nan ◽

Adrian J. Esterman ◽

...

Keyword(s):

Developing Countries ◽

Smoking Cessation ◽

Clinical Practice ◽

Chronic Disease ◽

Developed Countries ◽

Mental Illnesses ◽

Current Clinical Practice ◽

Efficacy And Safety ◽

First Line ◽

Marginalized Groups

Tobacco smoking remains the single most preventable cause of morbidity and mortality in developed countries and poses a significant threat across developing countries where tobacco use prevalence is increasing. Nicotine dependence is a chronic disease often requiring multiple attempts to quit; repeated interventions with pharmacotherapeutic aids have become more popular as part of cessation therapies. First-line medications of known efficacy in the general population include varenicline tartrate, bupropion hydrochloride, nicotine replacement therapy products, or a combination thereof. However, less is known about the use of these products in marginalized groups such as the indigenous, those with mental illnesses, youth, and pregnant or breastfeeding women. Despite the efficacy and safety of these first line pharmacotherapies, many smokers continue to relapse and alternative pharmacotherapies and cessation options are required. Thus, the aim of this review is to summarize the existing and developing pharmacotherapeutic and other options for smoking cessation, to identify gaps in current clinical practice, and to provide recommendations for future evaluations and research.

Download Full-text

Serum concentrations of antidepressants, antipsychotics, and antiepileptics over the bariatric surgery procedure

European Journal of Clinical Pharmacology ◽

10.1007/s00228-021-03182-1 ◽

2021 ◽

Author(s):

Susanna M. Wallerstedt ◽

Karin Nylén ◽

Magnus A. B. Axelsson

Keyword(s):

Bariatric Surgery ◽

Antiepileptic Drugs ◽

Therapeutic Drug ◽

Serum Concentrations ◽

Consistent Finding ◽

Low Calorie ◽

Post Surgery ◽

Low Calorie Diet ◽

Calorie Diet ◽

The Impact

Abstract Purpose As a substantial proportion of bariatric surgery patients use psychotropic/antiepileptic drugs, we investigated the impact of this procedure on serum concentrations. Methods In a naturalistic, longitudinal, prospective case series, we compared dose-adjusted trough concentrations of antidepressants, antipsychotics, or antiepileptics in consecutive patients before and after bariatric surgery. Adherence to treatment over 2 weeks preceding each sampling was considered. Results In all, 85 participants were included (86% female, median age 45 years, median body mass index 42 kg/m2). They were being treated with 18 different psychotropic/antiepileptic drugs (7 substances: 6–17 individuals, 11 substances: 1–4 individuals) and contributed 237 samples over a median of 379 days after surgery. For four out of seven substances with pre-/post-surgery samples available from six or more individuals, the dose-adjusted concentration was reduced (sertraline: 51%, mirtazapine: 41%, duloxetine: 35%, citalopram: 19%). For sertraline and mirtazapine, the low-calorie-diet before surgery entirely explained this reduction. A consistent finding, irrespective of drug, was the association between the mean ratio of the post-/pre-diet dose-adjusted concentration and the lipophilicity of the drug (logD; correlation coefficient: −0.69, P = 0.0005), the low-calorie diet often affecting serum concentration more than the surgery itself. Conclusions Serum concentrations of psychotropic/antiepileptic drugs vary after bariatric surgery and can be hard to predict in individual patients, suggesting that therapeutic drug monitoring is of value. Conversely, effects of the pre-surgery, low-calorie diet appear generalizable, with decreased concentrations of highly lipophilic drugs and increased concentrations of highly hydrophilic drugs. Interaction effects (surgery/dose/concentration) were not evident but cannot be excluded.

Download Full-text