Lacosamide adjunctive therapy for partial-onset seizures: a meta-analysis

Background. The relative efficacy and safety of lacosamide as adjunctive therapy compared to other antiepileptic drugs has not been well established.Objective. To determine if lacosamide provides improved efficacy and safety, reduced length of hospital stay and improved quality of life compared with other anti-epileptic therapies for adults with partial-onset seizures.Data Sources. A systematic review of the medical literature using Medline (1946–Week 4, 2012), EMBASE (1980–Week 3, 2012), Cochrane Central Register of Controlled Trials (Issue 1 of 12, January 2012). Additional studies were identified (through to February 7, 2012) by searching bibliographies, the FDA drug approval files, clinical trial registries and major national and international neurology meeting abstracts. No restrictions on publication status or language were applied.Study Selection. Randomized controlled trials of lacosamide in adults with partial-onset seizures were included.Data Extraction. Study selection, extraction and risk of bias assessment were performed independently by two authors. Authors of studies were contacted for missing data.Data Synthesis. All pooled analyses used the random effects model.Results. Three trials (1311 patients) met inclusion criteria. Lacosamide increased the 50% responder rate compared to placebo (RR 1.68 [95% CI 1.36 to 2.08]; I2 = 0%). Discontinuation due to adverse events was statistically significantly higher in the lacosamide arm (RR3.13 [95% CI 1.94 to 5.06]; I2 = 0%). Individual adverse events (ataxia, dizziness, fatigue, and nausea) were also significantly higher in the lacosamide group.Limitations. All dosage arms from the included studies were pooled to make a single pair-wise comparison to placebo. Selective reporting of outcomes was found in all of the included RCTs.Conclusions. Lacosamide as adjunctive therapy in patients with partial-onset seizures increases the 50% responder rate but with significantly more adverse events compared to the placebo

Chitosan and its derivatives as nanocarriers for siRNA delivery

The ability to specifically silence genes using siRNA has enormous potential for treating genetic diseases. However, siRNA instability and biodistribution issues still need to be overcome, and adequate delivery vehicles have proven indispensable in conveying siRNA to its target. Chitosan is a promising biopolymer for siRNA delivery, its interest stemming from its safety, biodegradability, mucoadhesivity, permeation enhancing effect and cationic charge, as well as amenability to undergo chemical modifications. Chitosan and its derivatives can be readily arranged into complexes or nanoparticles able to entrap and carry siRNA. Specific strategies have been adopted to improve chitosan-based vectors with regard to transfectability. However, further efforts are required to verify their value and adapt them to enhance therapeutic output prior to clinical application. This review emphasizes the potential of chitosan and its derivatives to develop nanocarriers for siRNA delivery. The properties of chitosan that are significant for transfectability and the most relevant findings are assessed

Cognitive effects of adjunctive perampanel for partial-onset seizures: A randomized trial

Objective Assess cognitive effects of adjunctive perampanel in adolescents. Methods In this double-blind study (ClinicalTrials.gov identifier: NCT01161524), patients aged 12 to <18 years with partial-onset seizures despite receiving 1–3 antiepileptic drugs were randomized (2:1) to perampanel or placebo. Perampanel was increased weekly in 2-mg increments to 8–12 mg/day (6-week titration; 13-week maintenance). Changes in neuropsychological outcomes were assessed at end of maintenance: Cognitive Drug Research (CDR) System Global Cognition Score (primary end point), five CDR System domain T-scores (secondary end points), letter fluency, category fluency, and Lafayette Grooved Pegboard Test (LGPT). Results One hundred thirty-three patients were randomized. In the full analysis set, there were no differences of perampanel (n = 79) vs. placebo (n = 44) in CDR System Global Cognition Score (least squares mean change, −0.6 vs. 1.6; p = 0.145), Quality of Working Memory (1.1 vs. 2.0; p = 0.579), or Power of Attention (−6.9 vs. −2.7; p = 0.219). There were small differences with perampanel vs. placebo in other CDR System domains: improvements in Quality of Episodic Memory (3.0 vs. −1.2; p = 0.012), and worsening in Continuity of Attention (−3.3 vs. 1.6; p = 0.013) and Speed of Memory (0.3 vs. 7.0; p = 0.032). Letter fluency, category fluency, and LGPT were not significantly different between groups. The most frequent adverse events with perampanel were dizziness (30.6%) and somnolence (15.3%). Significance Perampanel did not differ from placebo in the global cognitive score, two of five subdomains, and four other cognitive measures. Perampanel was worse on two and better on one subdomain