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- Ben-Menachem, Elinor, 1945
(författare)
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Pregabalin pharmacology and its relevance to clinical practice.
- 2004
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 45 Suppl 6, s. 13-8
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Forskningsöversikt (refereegranskat)abstract
- Pregabalin is a potent ligand for the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system that exhibits potent anticonvulsant, analgesic, and anxiolytic activity in a range of animal models. In addition, pregabalin has been shown to be a highly effective adjunctive therapy for partial seizures in clinical trials. Potent binding to the alpha-2-delta site reduces depolarization-induced calcium influx with a consequential modulation in excitatory neurotransmitter release. Pregabalin has no demonstrated effects on GABAergic mechanisms. Pregabalin demonstrates highly predictable and linear pharmacokinetics, a profile that makes it easy to use in clinical practice. Absorption is extensive, rapid, and proportional to dose. Time to maximal plasma concentration is approximately 1 h and steady state is achieved within 24-48 h. These characteristics reflect the observed onset of efficacy as early as day two in clinical trials. High bioavailability, a mean elimination half life (t(1/2)) of 6.3 h, and dose-proportional maximal plasma concentrations and total exposures predict a dose-response relationship in clinical practice and allow an effective starting dose of 150 mg/day in clinical practice without need for titration. Administration with food has no clinically relevant effect on the amount of pregabalin absorbed, providing for a dosing regimen uncomplicated by meals. Pregabalin does not bind to plasma proteins and is excreted virtually unchanged (<2% metabolism) by the kidneys. It is not subject to hepatic metabolism and does not induce or inhibit liver enzymes such as the cytochrome P450 system. Therefore, pregabalin is unlikely to cause, or be subject to, pharmacokinetic drug-drug interactions--an expectation that has been confirmed in clinical pharmacokinetic studies. However, dose adjustment may be necessary in patients with renal insufficiency. Thus, the pharmacological and pharmacokinetic profiles of pregabalin provide a predictable basis for its use in clinical practice.
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| 2. |
- Brodie, Martin J, et al.
(författare)
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Cannabinoids for epilepsy: What do we know and where do we go?
- 2018
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Ingår i: Epilepsia. - : Wiley. - 1528-1167 .- 1528-1167 .- 0013-9580. ; 59:2, s. 291-296
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Forskningsöversikt (refereegranskat)abstract
- Over the past decade there has been an increasing interest in using cannabinoids to treat a range of epilepsy syndromes following reports of some remarkable responses in individual patients. The situation is complicated by the fact that these agents do not appear to work via their attachment to endogenous cannabinoid receptors. Their pharmacokinetics are complex, and bioavailability is variable, resulting in difficulty in developing a suitable formulation for oral delivery. Drug interactions also represent another complication in their everyday use. Nevertheless, recent randomized, placebo-controlled trials with cannabidiol support its efficacy in Dravet and Lennox-Gastaut syndromes. Further placebo-controlled studies are underway in adults with focal epilepsy using cannabidivarin. The many unanswered questions in the use of cannabinoids to treat epileptic seizures are briefly summarized in the conclusion.
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| 4. |
- Johnson, Emma C, et al.
(författare)
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Physical activity in people with epilepsy: A systematic review.
- 2020
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Ingår i: Epilepsia. - : Wiley. - 1528-1167 .- 0013-9580.
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Forskningsöversikt (refereegranskat)abstract
- This study aimed to systematically review studies focusing on levels of physical activity (PA) in people with epilepsy (PWE) compared with non-epilepsy controls, and identify factors associated with PA in PWE. Intervention studies were also reviewed to consider the effects of psychological interventions on levels of PA, and the effects of PA-based interventions on seizure activity, psychiatric comorbidity, and health-related quality of life (HRQoL). PRISMA guidelines were followed. Searches were conducted using PubMed, Cochrane Controlled Register of Trials, PsycINFO, and Embase. Forty-six studies met inclusion criteria, including case-control, cross-sectional, and intervention studies. Assessment measures included questionnaires, activity trackers, and measures of physiological fitness. Twelve of 22 (54.5%) case-control studies utilizing self-report questionnaire measures reported that PWE were performing lower levels of PA, less likely to be engaging in PA, or less likely to meet PA guidelines than controls. The remaining studies did not find a difference between PWE and controls. Eight of 12 (67%) case-control studies utilizing exercise/fitness tests reported that PWE performed significantly poorer than controls, whereas in two studies PWE performed better than controls. One of three studies investigating the relationship between PA and seizure frequency found that increased self-reported PA was associated with having fewer seizures, whereas two did not find a significant relationship. All seven cross-sectional studies that included measures of HRQoL and depression/anxiety found a positive relationship between levels of PA and HRQoL/reduced levels of depression and anxiety. All four studies that used PA-based interventions demonstrated improvements in levels of PA and increased HRQoL. Study quality was almost universally low. In conclusion, there is some evidence that PWE engage in less PA than peers, and that interventions can improve PA levels and HRQoL. However, there is a need for more robust study designs to better understand PA in individuals with epilepsy.
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| 5. |
- Sauro, Khara M., et al.
(författare)
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The current state of epilepsy guidelines : A systematic review
- 2016
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 57:1, s. 13-23
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Forskningsöversikt (refereegranskat)abstract
- Objective: The International League Against Epilepsy (ILAE) Epilepsy Guidelines Task Force, composed of 14 international members, was established in 2011 to identify, using systematic review methodology, international epilepsy clinical care guidelines, assess their quality, and determine gaps in areas of need of development. Methods: A systematic review of the literature (1985-2014) was performed in six electronic databases (e.g. Medline, Embase) using a broad search strategy without initial limits to language or study design. Six gray literature databases (e.g., American Academy of Neurology [AAN], ILAE) were also searched to minimize publication bias. Two independent reviewers screened abstracts, reviewed full text articles, and performed data abstraction. Descriptive statistics and a meta-analysis were generated. Results: The search identified 10,926 abstracts. Of the 410 articles selected for full text review, 63 met our eligibility criteria for a guideline. Of those included, 54 were in English and 9 were in other languages (French, Spanish, and Italian). Of all guidelines, 29% did not specify the target age groups, 27% were focused on adults, 22% included only children, and 6% specifically addressed issues related to women with epilepsy. Guidelines included in the review were most often aimed at guiding clinical practice for status epilepticus (n = 7), first seizure (n = 6), drug-resistant epilepsy (n = 5), and febrile seizures (n = 4), among others. Most of the guidelines were therapeutic (n = 35) or diagnostic (n = 16) in nature. The quality of the guidelines using a 1-7 point scale (7 = highest) varied and was moderate overall (mean = 4.99 +/- 1.05 [SD]). Significance: We identified substantial gaps in topics (e.g., epilepsy in the elderly) and there was considerable heterogeneity in methodologic quality. The findings should offer a valuable resource for health professionals caring for people with epilepsy, since they will help guide the prioritization, development, and dissemination of future epilepsy-related guidelines.
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