Timothy Welty

• BSPharm, MA, PharmD
• Professor at Drake University

Since bromides were first used in 1857 to treat epilepsy, numerous antiseizure medications (ASM) have been developed. Many of these are available for the treatment of epilepsy and status epilepticus today. With so many ASM available, questions arise as to whether all of these medications are needed and when should they be used. As precision medicin...

In times of severe antiseizure medication (ASM) shortage due to emergency situations (e.g., disasters, conflicts, sudden disruption to international supply chains), management of people with epilepsy with available ASMs can be difficult. A group of experts was brought together by the International League Against Epilepsy (ILAE) to formulate recomme...

Some patients with epilepsy experience seizure clusters, which may be defined as 2 or more seizures occurring within 24 hours. Left untreated, seizure clusters increase the risk for physical injury and may progress to status epilepticus, irreversible neurologic injury, and death. Rescue therapy is based on benzodiazepine treatment. Prompt, appropri...

Background Status epilepticus (SE) is a neurologic emergency that can result in serious morbidity and mortality. Recent studies have suggested underdosing of both benzodiazepines (BZDs) and antiseizure medications (ASM) which may result in poorer outcomes. Objectives This study aims to determine the dose of BZDs and levetiracetam given in our emer...

The objective of this study was to identify and quantify barriers to generic substitution of antiseizure medications (ASM). A questionnaire on generic ASM substitution was developed by the International League Against Epilepsy (ILAE) Task Force on Generic Substitution. Questions addressed understanding of bioequivalence, standards for generic produ...

The objective of this analysis was to determine possible interactions between lamotrigine (LTG) and coffee or cigarette use. As part of the statistical analysis of factors influencing LTG pharmacokinetics (PK) in the Equigen chronic dose study, we collected prospective data from enrolled patients on their use of coffee and cigarettes. Subjects were...

The International League Against Epilepsy (ILAE) / American Epilepsy Society (AES) Task Force on the cardiac effects of lamotrigine was convened in response to a recent addition to the lamotrigine label by the US Food and Drug Administration (FDA).1 Lamotrigine is the nonproprietary name for a medicine that is sold under its generic name and severa...

Purpose: Established tonic-clonic status epilepticus (SE) does not stop in one-third of patients when treated with an intravenous (IV) benzodiazepine bolus followed by a loading dose of a second antiseizure medication (ASM). These patients have refractory status epilepticus (RSE) and a high risk of morbidity and death. For patients with convulsive...

Importance: Switching between generic antiepileptic drugs is a highly debated issue that affects both clinical care and overall health care costs. Objective: To evaluate the single-dose pharmacokinetic bioequivalence of 3 (1 branded and 2 generic drugs) on-market, immediate-release lamotrigine drug products. Design, setting, and participants:...

Background: Patients and clinicians share concerns that generic drug substitution might lead to loss of efficacy or emergence of adverse events. In this trial, we assessed US Food and Drug Administration (FDA) bioequivalence standards by studying the effects of switching between two disparate generic immediate-release lamotrigine products in patie...

A 2-semester project explored employing teams of fourth-year industrial engineering students to optimize some of our academic management processes. Results included significant cost savings and increases in efficiency, effectiveness, and student and faculty satisfaction. While we did not adopt all of the students’ recommendations, we did learn some...

Over the past few years, increasing public and political pressure has supported legalization of medical marijuana. One of the main thrusts in this effort has related to the treatment of refractory epilepsy—especially in children with Dravet syndrome—using cannabidiol (CBD). Despite initiatives in numerous states to at least legalize possession of C...

Purpose: Uncontrolled seizures negatively impact the quality of life among epilepsy patients, and bone health represents one of the more serious adverse outcomes due to epilepsy and its treatment. The objective of this study was to determine the association between seizure status (well-controlled vs. uncontrolled) and bone damage. Methods: A retr...

Due to concern and debate in the epilepsy medical community and to the current interest of the US Food and Drug Administration (FDA) in revising approaches to the approval of generic drugs, the FDA is currently supporting ongoing bioequivalence studies of antiepileptic drugs, the EQUIGEN studies. During the design of these crossover studies, the re...

To evaluate the safety, efficacy, pharmacokinetics, pharmacodynamic properties, and clinical application of ezogabine (retigabine, INN), an antiepileptic drug approved in 2011. Published data from in vitro, animal, and clinical studies were obtained from PubMed and CINAHL searches, from January 1980 to March 31, 2012. Other relevant data regarding...

For many questions related to the pharmacotherapy of epilepsy, there are few or no published data. This lack of data presents dilemmas to practitioners who must make informed, rational decisions about therapy on a daily basis and to policymakers dealing with drug formulary management and reimbursement. Reliance on randomized, clinical trial data is...

To systematically review the literature on generic antiepileptic drugs (AEDs), evaluate the efficacy and safety of generic AED substitution, and perform pharmacokinetic (PK) analysis using the American Academy of Neurology (AAN) scheme to classify evidence. PubMed and Cumulative Index to Nursing and Allied Health Literature searches from January 1,...

To determine whether limited transportation affects medication adherence in patients with epilepsy. Descriptive, nonexperimental, cross-sectional study. United States and worldwide, February to April 2007. 143 patients with epilepsy. A 22-item survey was developed to ask patients with epilepsy or their caregivers about the impact of limited transpo...

In 2008, the American College of Clinical Pharmacy appointed the Task Force on Research in the Professional Curriculum to review and make recommendations on the essential research curriculum that should be part of doctor of pharmacy (Pharm.D.) degree programs. The essential research curriculum provides all students with critical and analytical thin...

Background: Hallucinations and psychosis are common in patients with Parkinson's disease (PD), with reported prevalences of up to 48% and 80%, respectively. However, few randomized, double-blind, placebo-controlled trials evaluating the treatment options have appeared in the literature. The studies that have been published were complicated by lack...

This study aimed to assess the effectiveness and safety of naloxone in the management of hepatic encephalopathy (HE). Cochrane collaboration methodology was used in a meta-analysis of randomized controlled trials of naloxone therapy for HE. Seventeen randomized trials were identified with 15 studies involving 1054 patients meeting criteria for incl...

Individuals with epilepsy commonly experience memory loss. We investigated the safety and tolerability of galantamine in treatment of memory loss in a pilot study of 28 patients with epilepsy, randomly assigned to galantamine (n=13) or placebo (n=15) and followed for a total of 12 weeks. Participants underwent blinded memory assessment at baseline...

Generic substitution of antiepileptic drugs is an issue that is gathering a lot of attention in the neurology community but is not receiving much attention within pharmacy. Several proposals have been drafted that restrict a pharmacist's decision-making in generic substitution. These proposals highlight concerns about the pharmacy community related...

2006 marks the 40th year of publication for The Annals. Over that time, The Annals has been an important contributor to the development of clinical pharmacy. Throughout 2006, we are publishing articles reflecting on the history of clinical pharmacy through the eyes of practitioners, including those pioneering clinical pharmacy, as well as those who...

Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome that begins most frequently in the early teenage years. It is officially classified as a type of idiopathic generalized epilepsy and is often under-recognized or misdiagnosed. This syndrome has a strong genetic component with multiple gene mutations being associated with the clinical p...

1 While we appreciate their efforts to provide a careful review of available treatment guidelines and consideration of how these guidelines might be applied in managed care, we strongly disagree with their conclusion that older agents (i.e., phenobarbital, carbamazepine, phenytoin, and valproate) are the preferred first-line treatments for new-onse...

Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome that begins most frequently in the early teenage years. It is officially classified as a type of idiopathic generalized epilepsy and is often under-recognized or misdiagnosed. This syndrome has a strong genetic component with multiple gene mutations being associated with the clinical p...

To review available literature and provide perspective on point-of-care testing, focusing on the impact it has on treatment outcomes in patient care, the impact it has on the costs of patient care, and the role it has in the delivery of pharmaceutical care. Information was retrieved from MEDLINE English literature searches using PubMed (1965-August...

In replyWe appreciate the comments of Grunewald and colleagues. In their insightful remarks, they attempt to crystallize the present status of AEDs in the treatment of JME. They recommend separating seizure-free patients from those with infrequent seizures (<1 generalized tonic-clonic seizure a year or <5 single or cluster myoclonic seizures per mo...

Reversible neurotoxic symptoms were observed in three adult patients with absence status epilepticus on lamotrigine (LTG) therapy after administration of an IV bolus followed by oral valproic acid (VPA). Neurotoxicity was likely related to elevated serum LTG levels, as improvement correlated with discontinuing or reducing LTG dosage.

It is our experience that, on occasion, misinformation is disseminated on the nature and significance of warfarin protein-binding displacement interactions. Some healthcare workers are reluctant to add highly protein-bound drugs to a patient's warfarin therapy for fear of increasing significant bleeding episodes. A pharmacokinetically grounded rati...

To review the pharmacology, pharmacokinetics, efficacy, and adverse effects of levetiracetam in the treatment of epilepsy. A MEDLINE search restricted to English-language publications was conducted (January 1993-October 2000). Unpublished data provided by the manufacturer and information found in proceedings of professional meetings were also inclu...

Vagus nerve stimulation (VNS) has recently been introduced as an adjunct for treating patients with seizures. The aim of this systematic review was to overview the current evidence for the effects of vagus nerve stimulation, when used as an adjunctive treatment for patients with drug-resistant partial epilepsy. To determine the effects of VNS high-...

Prompt home treatment of dangerous seizures or upsetting relapses can prevent the effects of prolonged seizures and offer patients and their families an alternative to emergency medical treatment. The choice of benzodiazepine and route of administration should be based on patients' clinical presentation and acceptance. The challenge for the practit...

To characterize changes in seizure frequency following felbamate withdrawal. Nonrandomized, retrospective chart review of a case series. Epilepsy program specializing in adults with uncontrolled epilepsy. Forty-five ambulatory patients withdrawn from felbamate use. Patients were included if they had received felbamate for at least 1 month, were 18...

To review a case of a drug-drug interaction between phenytoin sodium and ticlopidine hydrochloride that resulted in acute phenytoin toxicity and permanent memory loss. A 63-year-old man who was maintained with a stable dose of phenytoin for treatment of seizures began treatment with ticlopidine following percutaneous transluminal angioplasty and st...

To document differences in the outcome of vancomycin therapy in patients managed through a therapeutic drug monitoring (TDM) service and patients managed empirically, without the participation of a TDM service. Prospective, cohort study. An 1100-bed, tertiary-care, teaching hospital. Those who received vancomycin for more than four days, were at le...

We report two cases of lost seizure control associated with the generic substitution of carbamazepine, review pertinent literature, and discuss the impact of this substitution on patient care. Case studies, abstracts, and research publications identified in MEDLINE and bibliographic review. One author reviewed cases supplied by the other authors an...

The pathophysiology and treatment of acute subarachnoid hemorrhage (SAH) are reviewed. SAH occurs when blood is released into the subarachnoid space, which surrounds the brain and spinal cord. Symptoms of SAH include severe headache, nausea, vomiting, neck pain, nuchal rigidity, and photophobia. The initial hemorrhage is fatal in 20-30% of patients...

Carbamazepine (CBZ) and carbamazepine 10,11 epoxide (CBZ‐E) concentrations were measured during a safety and efficacy trial of progabide. The average CBZ and CBZ‐E serum concentrations were calculated from serial measurements during placebo and active treatment periods. Significant decreases in CBZ and significant increases in CBZ‐E were observed a...

The delivery of paraldehyde in 5% dextrose injection and 0.9% sodium chloride injection was studied, and the potential interaction between paraldehyde and plastic i.v. containers and sets was evaluated. Paraldehyde was mixed with either 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags to form a 4% solution. T...

Progabide (PGB) is a gamma-aminobutyric acid (GABA)-agonist drug undergoing clinical evaluation for the treatment of spasticity, movement disorders, and epilepsy. Drug interactions were studied during a randomized, double-blind, crossover trial of the efficacy and toxicity of PGB in patients with partial seizures taking phenytoin (PHT) and carbamaz...

The chemistry, pharmacology, pharmacokinetics, adverse effects, dosage, and availability of nimodipine are discussed, and the clinical use of nimodipine in preventing and treating cerebral arterial spasm in patients with subarachnoid hemorrhage is reviewed. Nimodipine is a highly lipid-soluble dihydropyridine derivative that readily crosses the blo...

Twelve elderly institutionalized patients (mean age of 81 years) received intramuscular injections of tobramycin for infections at regular dosage intervals. The subjects had stable renal function but had limited mobility. Periodic blood specimens were collected for eight hours and analyzed for tobramycin by an immunofluorescence technique. The proc...

In an attempt to evaluate the accuracy of phenytoin (PHT) pharmacokinetic dosage adjustments in a private practice setting, three single dose‐concentration pair methods and three multiple point PHT pharmacokinetic dosing methods were studied. Dose and concentration data from 28 patients seen in a private neurology practice were utilized for the stu...

Anesthetic barbiturates have been used successfully to treat intractable seizures and increased intracranial pressure (ICP) in patients as young as six months old.1-3 Recently, our neonatal intensive-care unit cared for a newborn infant who was treated with pentobarbital coma to control seizures that were related to increased ICP and were refractor...

The first article in this series, published last month, acquainted readers with the basic principles of therapeutic drug monitoring and emphasized the value of this simple procedure in helping physician and patient reach their goal of optimal drug therapy. This month's article begins the analysis of specific therapeutic classes of drugs with a look...