Posts Tagged antiepileptic drugs

[Abstract] Pharmacology and epilepsy : update on the new antiepileptic drugs

New antiepileptic drugs are regularly approved for treatment and offer large therapeutic opportunities. Efficacy of these drugs is relatively similar on-label with different mechanisms to be combined for a synergic effect. Treatments such as cannabidiol have benefitted from large media coverage despite limited clinical evidence so far. The objective of antiepileptic drugs is to stop the recurrence of epileptic seizures with as few adverse events as possible. When confronted to a difficult-to-treat epilepsy, referral to a specialised centre is strongly advised. The aim is to confirm that the diagnosis is correct, that the treatment is well adapted (indication, pharmacokinetic and compliance) and to evaluate the indication for non-pharmacological treatments such as epilepsy surgery.

 

via [Pharmacology and epilepsy : update on the new antiepileptic drugs]. – Abstract – Europe PMC

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[Abstract] Antiepileptic drug treatment during pregnancy and delivery in women with epilepsy – A retrospective single center study

Highlights

Pregnancies in women with epilepsy (WWE) increased significantly during our 11-year study period (41% increase).

Twelve different AEDs were prescribed to WWE during pregnancies in the 11-year period investigated (2005-2015) with Lamotrigine (36.1%), Carbamazepine (25.0%), and Valproic Acid (13.5%) most commonly used.

Valproic acid use was markedly reduced comparing the years 2005-2010 (18.4%) and 2011-2015 (9.4%), a reduction of 48%.

Unfortunately, a trend towards an increase in treating WWE with more than one AED was observed.

Cover image Epilepsy ResearchAbstract

Purpose

Antiepileptic drugs (AED) are among the most common teratogenic drugs prescribed to women of childbearing age. During pregnancy, the risk of seizures has to be weight against the use of AED treatment. Primary goal was to observe and describe AED treatment policy and its changes during an eleven-year period at our third referral center.

Methods

We scrutinized the medical health records for all cases of female epileptic patients admitted for labor at the Rabin Medical Center during the years 2005 – 2015.

Results

A total of 296 deliveries were recorded with 136 labors occurring in the period 2005-2010 (22.7/y) and 160 in 2011-2015 (32.0/y; increase of 41%). Twelve different AEDs were prescribed to WWE during pregnancies in the 11-year period investigated (2005-2015). Most commonly used AEDs during pregnancy were Lamotrigine (36.1%), Carbamazepine (25.0%), and Valproic Acid (13.5%). Comparing their use during the years 2005-2010 and 2011-2015, Lamotrigine (35.3% vs. 36.9%) and Carbamazepine use (23.5% vs. 26.0%) increased slightly. Valproic acid use was markedly reduced in the second period: 18.4% in the years 2005-2010 lowered to 9.4% during 2011-2015, a reduction of 48%. Unfortunately, a trend towards an increase in treating WWE with more than one AED was observed.

Conclusions

The proportion of WWE treated with VPA during pregnancy was significantly reduced in the observed period (2005-2015). Change in fetal outcome during this period for WWE could not be detected.

via Antiepileptic drug treatment during pregnancy and delivery in women with epilepsy—A retrospective single center study – ScienceDirect

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[REVIEW] Summary of Antiepileptic Drugs Available in the United States of America – AMERICAN EPILEPSY SOCIETY

The current review summarizes the
main antiepileptic drugs available for
prescription in the United States as of
July 2018. One condensed, and one
expanded, table of the major properties
of 28 AEDs are presented both
to assist clinicians in providing care to
persons with epilepsy and to facilitate
the training of those in health care
educational programs.

This table is not intended to constitute
recommendations, only to provide an
easy reference listing of products on
the market.

Download Table (PDF)

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[Abstract] Affective and behavioral dysfunction under antiepileptic drugs in epilepsy: Development of a new drug-sensitive screening tool

Highlights

  • Behavioral problems (e.g., depression) in epilepsy are common but usually of mild severity.
  • 30 AED-sensitive items were discerned from the BDI-I, NDDI-E, and FPZ.
  • Items were classified into six scales, constituting the new screening tool “PsyTrack”.
  • PsyTrack subscale scores differed as a function of drug load and presence of AEDs with negative psychotropic effects.
  • Generally, monotherapy seems to be favorable in terms of behavioral adverse effects.

Abstract

Objective

Behavioral problems and psychiatric symptoms are common in patients with epilepsy and have a multifactorial origin, including adverse effects of antiepileptic drugs (AEDs). In order to develop a screening tool for behavioral AED effects, the aim of this study was to identify behavioral problems and symptoms particularly sensitive to AED drug load and the presence/absence of AEDs with known negative psychotropic profiles.

Methods

Four hundred ninety-four patients with epilepsy were evaluated who had been assessed with three self-report questionnaires on mood, personality, and behavior (Beck Depression Inventory, BDI; Neurological Disorders Depression Inventory for Epilepsy extended, NDDI-E; and Fragebogen zur Persönlichkeit bei zerebralen Erkrankungen, FPZ). Drug-sensitive items were determined via correlation analyses and entered into an exploratory factor analysis for scale construction. The resulting scales were then analyzed as a function of drug treatment.

Results

Analyses revealed 30 items, which could be allocated to six behavioral domains: Emotional LabilityDepressionAggression/IrritabilityPsychosis & SuicidalityRisk- & Sensation-seeking, and Somatization. Subsequent analysis showed significant effects of the number of AEDs on behavior, as in Emotional Lability (F = 2.54, p = .029), Aggression/Irritability (F = 2.29, p = .046), Psychosis & Suicidality (F = 2.98, p = .012), and Somatization (F = 2.39, p = .038). Affective and behavioral difficulties were more prominent in those patients taking AEDs with supposedly negative psychotropic profiles. These effects were largely domain-unspecific and primarily manifested in polytherapy.

Conclusion

Drug-sensitive behavioral domains and items were identified which qualify for a self-report screening tool. The tool indicates impairments with a higher drug load and when administering AEDs with negative psychotropic profiles. The next steps require normalization in healthy subjects and the clinical validation of the newly developed screening tool PsyTrack along with antiepileptic drug treatment.

via Affective and behavioral dysfunction under antiepileptic drugs in epilepsy: Development of a new drug-sensitive screening tool – Epilepsy & Behavior

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[Abstract] Therapeutic Drug Monitoring of Antiepileptic Drugs in Epilepsy: A 2018 Update

Abstract

Backgrounds:

Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment. Since 1989, 18 new AEDs have been licensed for clinical use and there are now 27 licensed AEDs in total for the treatment of patients with epilepsy. Furthermore, several AEDs are also used for the management of other medical conditions, e.g., pain and bipolar disorder. This has led to an increasingly widespread application of therapeutic drug monitoring (TDM) of AEDs, making AEDs among the most common medications for which TDM is performed. The aim of this review is to provide an overview of the indications for AED TDM, to provide key information for each individual AED in terms of the drug’s prescribing indications, key pharmacokinetic characteristics, associated drug-drug pharmacokinetic interactions and the value and the intricacies of TDM for each AED. The concept of the reference range is discussed as well as practical issues such as choice of sample types (total vs free concentrations in blood vs saliva) and sample collection and processing.

Methods:

The present review is based on published articles and searches in PubMed and Google Scholar, last searched March in 2018, in addition to references from relevant papers.

Results:

In total, 171 relevant references were identified and used to prepare this review.

Conclusions:

TDM provides a pragmatic approach to epilepsy care in that bespoke dose adjustments are undertaken based on drug concentrations so as to optimize clinical outcome. For the older first generation AEDs (carbamazepine, ethosuximide, phenobarbital, phenytoin, primidone and valproic acid), much data has accumulated in this regard. However, this is occurring increasingly for the new AEDs (brivaracetam, eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, piracetam, pregabalin, rufinamide, stiripentol, sulthiame, tiagabine, topiramate, vigabatrin and zonisamide).

via Therapeutic Drug Monitoring of Antiepileptic Drugs in Epilepsy: A 2018 Update

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[Abstract] Pharmacotherapy of epilepsy

Pharmacotherapy of epilepsy is usually initiated after two or more unprovoked seizures, a decision that should be made after assessment of the individual risk of further seizures. Antiepileptic drugs (AEDs) are selected based on documented efficacy for the type of seizures, the epilepsy and possible epilepsy syndrome of the patient, taking potential adverse effects and comorbidity into account. For many AEDs, the mechanisms of action are incompletely understood. More than half of patients with newly diagnosed epilepsy achieve sustained seizure freedom with their first or second drug trials. After a prolonged time of seizure freedom discontinuation of therapy may be considered; the risk of relapse after drug withdrawal can be estimated on the basis of a number of clinical factors. The informed patient’s attitude is essential in all therapy decisions. Treatment is still largely symptomatic, but the future may involve a greater degree of disease-modifying precision medicine.

via [Pharmacotherapy of epilepsy]. – Abstract – Europe PMC

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[WEB SITE] Medication Adherence Key to Epilepsy Treatment

In assessing the effectiveness of prescribed medication there is a strong emphasis on the ability of the patient to adhere to the regime recommended by the clinician. For individuals with epilepsy, adherence to medication is crucial in preventing or minimizing seizures and their cumulative impact on everyday life. Non-adherence to antiepileptic drugs (AEDs) can result in breakthrough seizures many months or years after a previous episode and can have serious repercussions on an individual’s perceived quality of life. Reasons for non-adherence are complex and multilayered. Patients can accidentally fail to adhere through forgetfulness, misunderstanding, or uncertainty about clinician’s recommendations, or intentionally due to their own expectations of treatment, side-effects, and lifestyle choice.

Adherence in epilepsy

Adherence is acting in accordance with advice, recommendations or instruction. Ways that adherence can be optimized;

  1. Educating individuals and their families and carers in understanding of their condition and the rationale of treatment, reducing the stigma associated with the conditions.
  2. Using simple medication regimes.
  3. Positive relationships between healthcare professionals, the individual with epilepsy and their family and /or carers.
  4. Other measures are; manual telephones follow up, home visits, special reminders, regular appointments/ refill reminders.

While failing to adhere to treatment plans can adversely affect individuals with any general medical condition, Non- adherence to anti-epileptic drugs results to increased risk of status epilepticus (prolonged seizures) resulting into brain damage, SUDEP, risk of injuries, increase rates of admission to hospital due prolonged seizures. The consequences of not taking medication can be more immediate with epilepsy.​

Epilepsy as a chronic condition relies heavily on adherence to medical advice in order to maximize an individual’s quality of life by controlling seizures more effectively while avoiding unwanted side-effects. Treatment of those diagnosed with epilepsy the vast majorities are treated with AEDs and approximately 70% can become seizure-free once the most effective regime is followed.

Monotherapy is viewed as the initial and preferential option for treating epilepsy, the choice of drug depending on seizure type and effectiveness of the drug balanced against possible side-effects. It is difficult to find estimates of how many people are on monotherapy or polytherapy at any one point in time.

However, in one of the cases I encountered that of Sarafina Muthoni from Banana, Kiambu County, she was diagnosed with Epilepsy at a very young age in her primary school days. With no history of such a condition in her family, it got everybody thinking what could have gone wrong with their lovely daughter. After days of trying to figure out, the family had to adapt to reality of their daughter living with Epilepsy. She was lucky to have very supportive parents ready to see her through the long journey of treating the condition. The motivation and support from her loved ones to access medication improved her status by far as she continued to adhere to the prescribed treatment. Unfortunately, the support didn’t last long and the burden of continuing with treatment squarely relied on her. This adversely contributed to the beginning of non-adherence to medication for lack of funds to buy drugs. Not only were finances a challenge but also finding a good hospital to comply was a problem.

Muthoni had to live with the sad reality of pain every time she experienced a seizure. Pain which she clearly knew with access to medication the situation could by far be controlled. At the very worse of her situation she found help. Cheshire Disability Services Kenya (CDSK) a Non-Governmental Organization in Kenya whose objective is to empower an inclusive society of persons with disability and develop their full potential to lead a quality life, in partnership with Kenya Association of People with Epilepsy (KAWE) came for Muthonis’ rescue.

Under CDSK’s program to help Epilepsy patients’ access medication and ensure compliance, Muthoni benefited and today she leads a life full of potential and energy as she explores her skills as a beauty and hair stylist.

As we celebrate International Epilepsy Day on Feb 12th 2018, themed on “Life is beautiful”, Muthoni’s story is a highlight of what beauty is all about. Hers’ is just but one of the many inspiring stories to celebrate during this season of Epilepsy Awareness.

Managing Adherence

Adherence to medication regardless of medical condition remains an important problem in treatment. Factors that have been discussed here – side-effects, drug regime, family support, impact on everyday life, relationship with the clinician – are unlikely to be the only predictors of adherence. While adherence to treatment within the context of epilepsy has been the focus of this review, these factors can equally be applied to various chronic conditions.

Assessment of adherence should be a routine part of management of epilepsy. Further recognition and support should be given to patients who have poor seizure control since they are more likely to be more anxious and have unhelpful illness and treatment beliefs.

Finally, patients may be fully aware of the importance of taking AED medication and the benefits gained by altering their lifestyle choices in order to prevent seizures, but will make a decision about the degree to which they follow advice. Patients only have a small amount of time in contact with the clinician in their “patient role”, after which they return to the practicalities of their everyday routine where their adherence fluctuates based on how they feel their medication affects their quality of life.

Strategies to manage adherence originate from different perspectives. While the medical model may advocate less complex drug regimes, the use of measured pill containers, and minimization of side-effects, the psychosocial model analyzes non-adherence in terms of patient attitudes to medication, stigma, family and peer influences, and ability to manage self care. Neither model can adequately improve adherence independently. Perhaps the best approach is to offer a “menu” of adherence-enhancing strategies. However, what is increasingly clear from both models is that total adherence is an unrealistic goal. The emphasis has shifted away from total adherence towards a compromise with both patient and clinician involved in a joint process of treatment negotiation and decision-making in order to achieve the best outcome for the individual.

 

via Medication Adherence Key to Epilepsy Treatment : Evewoman – The Standard

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[WEB SITE] AEDs: Which Work Best as Monotherapy in Epilepsy? – Neurology Times

Which antiepileptic drugs (AEDs) are best as monotherapy? Before the updated Cochrane review, first-line therapy in adults and children with partial onset seizures was with carbamazepine or lamotrigine. And first-line therapy for generalized seizure onset was with sodium valproate.

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  • 60%-70% of people with epilepsy reach remission from seizures shortly after starting AED treatment. Most are treated with AED monotherapy. The National Institute for Health and Care Excellence (NICE) guidelines in the UK recommend carbamazepine or lamotrigine as first-line-therapy in adults and children with partial onset seizures and sodium valproate as first-line for generalized onset seizures. A 2007 network meta-analysis of AED monotherapy generally agreed with these recommendations.[1]

     

  • The Cochrane Review of AED monotherapy, which updates previous meta-analysis with studies published since 2007, adds levetiracetam and zonisamide.[2]

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  • Individual participant data (IPD) approach were used; considered gold standard for time-to-event pooled network meta-analysis. Combined IPD data from 12,391 people in 36 studies and compared 10 AEDS: carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, zonisamide. ooled data from trials that did head-to-head comparisons were analyzed; a second analysis combined all data from trials to compare drugs that had not been previously compared.

  • For partial seizures, levetiracetam was found to be significantly better than carbamazepine and lamotrigine. Lamotrigine was significantly better than all other AEDs (except levetiracetam). And carbamazepine was significantly better than gabapentin and phenobarbitone. For generalized onset seizures, valproate was significantly better than carbamazepine, topiramate and phenobarbitone. For both partial and generalized onset seizures: phenobarbitone, the earliest licensed treatment, performed worse in terms of treatment failure than all other treatments.

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  • There were few notable differences for partial or generalized seizure types, except fpr 12-month remission: Carbamazepine was significantly better than levetiracetam for partial seizures; and 6-month remission: Sodium valproate was significantly better than lamotrigine for generalized seizures. Regarding time to bot partial and generalized seizures: the oldest AEDs (phenytoin and phenobarbitone) were generally better than newer AEDs. The most commonly reported adverse events across all drugs: drowsiness/fatigue, headache/migraine, GI disturbances, dizziness/faintness, rash/skin disorders.

  • IPD data were available for just 69% of total participants from 47% of eligible trials, leaving out 31% of eligible participants. Methodological inadequacies in some trials could have biased results

  • 1. Phenobarbitone and phenytoin are better for seizure control, but at the expense of earlier treatment failure. 2. Carbamazepine and lamotrigine are suitable as first-line monotherapy for partial onset seizures; levetiracetam may be a suitable alternative. 3. Sodium valproate is suitable as first-line monotherapy for generalized seizures; lamotrigine and levetiracetam may be suitable alternatives, especially for women of child-bearing age given the potential teratogenicity of sodium valproate 4. Zonisamide may effective in partial onset seizures: evidence is limited and more research is needed.

1. Tudur Smith C, Marson AG, Chadwick DW, Williamson PR. Multiple treatment comparisons in epilepsy monotherapy trials. Trials. 2007;5(8):34
2. Nevitt SJ, Sudell M, Weston J, Tudur Smith C, Marson AG. Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data. Cochrane Database of Systematic Reviews. 2017, Issue 6. Art. No. CD011412.

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Which AEDs work best as monotherapy?

A new Cochrane review scrutinizes the efficacy and tolerability of various agents.

 

via AEDs: Which Work Best as Monotherapy in Epilepsy? | Neurology Times

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[WEB SITE] Compound derived from marijuana interacts with antiepileptic drugs

New research published in Epilepsia, a journal of the International League Against Epilepsy (ILAE), suggests that an investigational neurological treatment derived from cannabis may alter the blood levels of commonly used antiepileptic drugs. It is important for clinicians to consider such drug interactions during treatment of complex conditions.

Cannabidiol (CBD), a compound developed from the cannabis plant, is being studied as a potential anticonvulsant, and it has demonstrated effectiveness in animal models of epilepsy and in humans. An ongoing open label study (Expanded Access Program) conducted by investigators at the University of Alabama at Birmingham is testing the potential of CBD as a therapy for children and adults with difficult to control epilepsy. The study includes 39 adults and 42 children, all of whom receive CBD.

Because all of the participants are also taking other seizure drugs while they are receiving the investigational therapy, investigators checked the blood levels of their other seizure drugs to see if they changed. “With any new potential seizure medication, it is important to know if drug interactions exist and if there are labs that should be monitored while taking a specific medication,” said lead author Tyler Gaston, MD.

Dr. Gaston and her colleagues found that there were significant changes in levels of the drugs clobazam (and its active metabolite N-desmethylclobazam), topiramate, and rufinamide in both adults and children, and zonisamide and eslicarbazepine in adults only. Except for clobazam/desmethylclobazam, however, the drug levels did not change outside of the normally accepted range. In addition, adult participants in the study taking clobazam reported sedation more frequently.

Tests also showed that participants taking valproate and CBD had higher ALT and AST (liver function tests) compared with participants not taking valproate. Very high ALT and AST indicate abnormal liver function, but significant ALT and AST elevation occurred only in a mall number of participants (4 children and 1 adult), and the levels returned to normal after discontinuation of valproate and CBD.

“While the interaction between CBD and clobazam has been established in the literature, there are currently no published human data on CBD’s potential interactions with other seizure medications,” said Dr. Gaston. “However, given the open label and naturalistic follow-up design of this study, our findings will need to be confirmed under controlled conditions.”

The findings emphasize the importance of monitoring blood levels of antiepileptic drugs as well as liver function during treatment with CBD. “A perception exists that since CBD is plant based, that it is natural and safe; and while this may be mostly true, our study shows that CBD, just like other antiepileptic drugs, has interactions with other seizure drugs that patients and providers need to be aware of,” said Dr. Gaston.

Article: Interactions between cannabidiol and commonly used antiepileptic drugs, Tyler E. Gaston, E. Martina Bebin, Gary R. Cutter, Yuliang Liu, Jerzy P. Szaflarski, and for the UAB CBD Program, Epilepsia, doi: 10.1111/epi.13852, published online 6 August 2017.

Source: Compound derived from marijuana interacts with antiepileptic drugs

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[Abstract] Post-stroke epilepsy

Highlights

Post-stroke epilepsy (PSE) is a major complication after stroke.

It is unclear which treatments are most effective in the prevention of recurrence of symptoms, or whether such therapy is needed for primary prevention.

The current understanding of epidemiology, diagnoses, mechanisms, risk factors, and treatments of PSE are covered in this review.

Abstract

Post-stroke epilepsy (PSE) is a common complication after stroke, yet treatment options remain limited. While many physicians prescribe antiepileptic drugs (AED) for secondary prevention of PSE, it is unclear which treatments are most effective in the prevention of recurrence of symptoms, or whether such therapy is needed for primary prevention. This review discusses the current understanding of epidemiology, diagnoses, mechanisms, risk factors, and treatments of PSE.

Source: Post-stroke epilepsy

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