The effects of different acetylcholinesterase inhibitors on EEG patterns in patients with Alzheimer's disease: A systematic review.

OBJECTIVE: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common type of dementia. The early diagnosis of AD is an important factor for the control of AD progression. Electroencephalography (EEG) can be used for early diagnosis of AD. Acetylcholinesterase inhibitors (AChEIs) are also used for the amelioration of AD symptoms. In this systematic review, we reviewed the effect of different AChEIs including donepezil, rivastigmine, tacrine, physostigmine, and galantamine on EEG patterns in patients with AD. METHODS: PubMed electronic database was searched and 122 articles were found. After removal of unrelated articles, 24 articles were selected for the present study. RESULTS: AChEIs can decrease beta, theta, and delta frequency bands in patients with AD. However, conflicting results were found for alpha band. Some studies have shown increased alpha frequency, while others have shown decreased alpha frequency following treatment with AChEIs. The only difference was the type of drug. CONCLUSIONS: We found that studies reporting the decreased alpha frequency used donepezil and galantamine, while studies reporting the increased alpha frequency used rivastigmine and tacrine. It was suggested that future studies should focus on the effect of different AChEIs on EEG bands, especially alpha frequency in patients with AD, to compare their effects and find the reason for their different influence on EEG patterns. Also, differences between the effects of AChEIs on oligodendrocyte differentiation and myelination may be another important factor. This is the first article investigating the effect of different AChEIs on EEG patterns in patients with AD.

Felbamate urolithiasis.

Drug-induced nephrolithiasis is an important consideration in recurrent stone formers with polypharmacy. While felbamate nephrolithiasis has previously been published in the paediatric population, we present the oldest published case of a felbamate stone in an adult, a man in his 30s with Lennox-Gastaut syndrome. Even with moderate dosing, high drug serum levels can occur. Performing at least one stone analysis remains a critical component to care in these patients. Urologists should have a high index of suspicion for drug stone when stone analysis returns indeterminate characterisation in the absence of infection. Close communication with neurology is key to preventing recurrent stone disease.

Consumption of drugs for Alzheimer's disease on the Brazilian private market.

OBJECTIVE: To analyze the consumption of drugs for Alzheimer's disease on the Brazilian private market and its geographical distribution from 2014 to 2020. METHODS: National data from the Brazilian National System of Controlled Product Management were used, regarding sales of donepezil, galantamine, rivastigmine, and memantine from January 2014 to December 2020. Sales data were used as a proxy for drug consumption and expressed as defined daily dose/1,000 inhabitants/year at national, regional, federative unit and microregion levels. RESULTS: Drug consumption went from 5,000 defined daily doses/1,000 inhabitants, in 2014, to more than 16,000/1,000 inhabitants, in 2020, and all federative units showed positive variation. The Brazilian Northeast had the highest cumulative consumption in the period but displayed microregional disparities while the North region had the lowest consumption. Donepezil and memantine were the most consumed drugs, with the highest growth in consumption from 2014 to 2020. CONCLUSION: The consumption of medicines indicated to treat Alzheimer's disease tripled in Brazil between 2014 and 2020, which may relate to the increase in the prevalence of the disease in the country, greater access to health services, and inappropriate use. This challenges managers and healthcare providers due to population aging and the increased prevalence of chronic-degenerative diseases.

Prevalence of treated patients with Alzheimer's disease: current trends and COVID-19 impact.

BACKGROUND: There are few updated studies on the prevalence and management of Alzheimer's disease (AD), which could be underdiagnosed or undertreated. The COVID-19 pandemic may have worsened the deficiencies in the diagnosis and treatment of these patients. Electronic medical records (EMR) offer an opportunity to assess the impact and management of medical processes and contingencies in the population. OBJECTIVE: To estimate AD prevalence in Spain over a 6-year period, based on treated patients, according to usual clinical practice. Additionally, to describe the management of AD-treated patients and the evolution of that treatment during the 2020 COVID-19 pandemic. METHODS: Retrospective study using the Spanish IQVIA EMR database. Patients treated with donepezil, galantamine, rivastigmine, and/or memantine were included in the study. Annual AD prevalence (2015-2020) was estimated and extrapolated to the national population level. Most frequent treatments and involved specialties were described. To assess the effect of COVID-19, the incidence of new AD cases in 2020 was calculated and compared with newly diagnosed cases in 2019. RESULTS: Crude AD prevalence (2015-2020) was estimated at 760.5 per 100,000 inhabitants, and age-standardized prevalence (2020) was 664.6 (male 595.7, female 711.0). Monotherapy was the most frequent way to treat AD (86.2%), in comparison with dual therapy (13.8%); rivastigmine was the most prescribed treatment (37.3%), followed by memantine (36.4%) and donepezil (33.0%). Rivastigmine was also the most utilized medication in newly treated patients (46.7%), followed by donepezil (29.8%), although donepezil persistence was longer (22.5 vs. 20.6 months). Overall, donepezil 10 mg, rivastigmine 9.5 mg, and memantine 20 mg were the most prescribed presentations. The incidence rate of AD decreased from 148.1/100,000 (95% confidence interval [CI] 147.0-149.2) in 2019 to 118.4/100,000 (95% CI 117.5-119.4) in 2020. CONCLUSIONS: The obtained prevalence of AD-treated patients was consistent with previous face-to-face studies. In contrast with previous studies, rivastigmine, rather than donepezil, was the most frequent treatment. A decrease in the incidence of AD-treated patients was observed during 2020 in comparison with 2019, presumably due to the significant impact of the COVID-19 pandemic on both diagnosis and treatment. EMR databases emerge as valuable tools to monitor in real time the incidence and management of medical conditions in the population, as well as to assess the health impact of global contingencies and interventions.

Effect of Acetylcholinesterase Inhibitors on Cerebral Perfusion and Cognition: A Systematic Review.

BACKGROUND: Perfusion imaging has the potential to identify neurodegenerative disorders in a preclinical stage. However, to correctly interpret perfusion-derived parameters, the impact of perfusion modifiers should be evaluated. OBJECTIVE: In this systematic review, the impact of acute and chronic intake of four acetylcholinesterase inhibitors (AChEIs) on cerebral perfusion in adults was investigated: physostigmine, donepezil, galantamine, and rivastigmine. RESULTS: Chronic AChEI treatment results in an increase of cerebral perfusion in treatment-responsive patients with Alzheimer's disease, dementia with Lewy bodies, and Parkinson's disease dementia in the frontal, parietal, temporal, and occipital lobes, as well as the cingulate gyrus. These effects appear to be temporary, dose-related, and consistent across populations and different AChEI types. On the contrary, further perfusion decline was reported in patients not receiving AChEIs or not responding to the treatment. CONCLUSION: AChEIs appear to be a potential perfusion modifier in neurodegenerative patients. More research focused on quantitative perfusion in both patients with and without a cholinergic deficit is needed to draw conclusions on whether AChEI intake should be considered when analyzing perfusion data.

A Comprehensive Computational Perspective in Drug Discovery for Alzheimer's Disease.

Alzheimer's Disease (AD), the most common and major disability issue in our society, has a substantial economic impact. Despite substantial advances in aetiology, diagnosis, and therapy, the fundamental causes of the disease remain unknown, accurate biomarkers are not well characterized, and current pharmaceutical medications are not cost-effective. Effective care for Alzheimer's disease and other types of dementia is crucial for patients' long-term health. Pathogenesis advances have aroused the scientific community's interest in the creation of new pharmacological treatments that target recognized disease targets throughout the previous two decades. Pharmacological therapy has recently been assigned 10 - 20% of the direct costs of AD. Less than 20% of Alzheimer's patients respond somewhat to standard medicines with questionable cost-effectiveness (donepezil, galantamine, memantine and rivastigmine). Therefore, currently known treatment approaches address the condition indirectly, as acetyl cholinesterase related inhibitors and the Nmethyl d-aspartate as receptor and antagonists have little effect on the sickness. Novel targets and specific small molecules must also be found in order to be useful in the therapy of AD. This chapter examines a wide spectrum of Alzheimer's disease targets as well as contemporary progress in the discovery of disease inhibitors. In addition, brief in-silico investigations were highlighted and provided to understand how the theoretical lead in AD treatment development is attainable.

Real-world effects of anti-dementia treatment on mortality in patients with Alzheimer´s dementia.

To examine the real-world effects of the cholinesterase inhibitors (AChEI) on all-cause mortality. A nationwide, retrospective cohort study. Participants were diagnosed with incident AD in Denmark from January 1, 2000 to December 31, 2011 with follow-up until December 31, 2012. A total of 36,513 participants were included in the current study with 22,063 deaths during 132,426 person-years of follow-up. At baseline, patients not treated with AChEI (n = 28,755 [9961 males (35%)]) had a mean age ±â€…standard deviation (SD) of 80.33 ±â€…7.98 years (78.97 ±â€…8.26 for males and 81.04 ±â€…7.98 for females), as compared to 79.95 ±â€…7.67 (78.87 ±â€…7.61 for males and 80.61 ±â€…7.63 for females) in the group exposed at baseline. Patients treated with AChEI had a beneficial hazard ratio (HR) of 0.69, 95% confidence interval (CI) (0.67-0.71) for all-cause mortality as compared to patients not treated, with donepezil (HR 0.80, 95% CI [0.77-0.82]) and galantamine (HR 0.93,95% CI [0.89-0.97]) having beneficial effects on mortality rate as compared to non-treatment, whereas rivastigmine (HR 0.99, 95% CI [0.95-1.03]) was associated with a mortality rate comparable to non-treatment with AChEI. Patients were primarily exposed to donepezil (65.8%) with rivastigmine (19.8%) and galantamine (14.4%) being used less often. These findings underscore the effect of AChEI on not only reducing speed of cognitive decline but also directly prolonging life, which could result in changes in treatment recommendation for when to stop treatment.

The listed, delisted, and sustainability of therapeutic medicines for dementia patients: the study is specific to South Korea.

The Dementia Management Act (DMA) came into effect on August 4, 2011, in South Korea. Diagnosis and medication were rapidly performed for dementia in a short time. We investigated the cardiac effects of increased drug prescription following DMA. We observed a correlation between Alzheimer's disease (AD) and anti-AD drug (AAD) groups from 2010 to 2019 on the National Health Insurance System (NHIS) of South Korea. This study investigated the increase and decrease in deaths of AD patients with AAD. We analysed the mortality per 100,000 population with the R2 Calculator. Moreover, we made the up or down datum line for the simple decision on the listed, delisted, and sustainable drug examined by a linear equation and R2. We observed that life expectancy was diminished by AAD in Sorokdo National Hospital. In the NHIS, donepezil and rivastigmine increased the number of deaths decided on R2 > 0.75. Memantine was sustainable. We could not decide on galantamine because it is one of the other groups. We made a straightforward decision-maker of delisted, listed, or sustainable criteria based on mortality and datum line.

Global trends in symptomatic medication use against dementia in 66 countries/regions from 2008 to 2018.

BACKGROUND AND PURPOSE: The aim was to determine trends and patterns of symptomatic medication used against dementia in 66 countries and regions. METHODS: This was a cross-sectional study that used the wholesale data from the IQVIA Multinational Integrated Data Analysis System database. Sale data for symptomatic medication against dementia from 66 countries and regions from 2008 to 2018 were analysed and stratified by income level (low/middle-income countries [LMICs], n = 27; high-income countries [HICs], n = 37; regions, n = 2). The medication use volume was estimated by defined daily dose (DDD) per 1000 inhabitants per day (World Health Organization DDD harmonized the size, strength and form of each pack and reflects average dosing). Changes in medication use over time were quantified as percentage changes in compound annual growth rates (CAGRs). RESULTS: Total symptomatic medication against dementia sales increased from 0.85 to 1.33 DDD per 1000 inhabitants per day between 2008 and 2018 (LMICs 0.094-0.396; HICs 3.88-5.04), which is an increase of CAGR of 4.53% per year. The increase was mainly driven by the LMICs (CAGR = 15.42%) in comparison to the HICs (CAGR = 2.65%). The overall medication use from 2008 to 2018 increased for all four agents: memantine (CAGR = 8.51%), rivastigmine (CAGR = 6.91%), donepezil (CAGR = 2.72%) and galantamine (CAGR = 0.695%). In 2018, the most commonly used medication globally was donepezil, contributing to 49.8% of total use volume, followed by memantine (32.7%), rivastigmine (11.24%) and galantamine (6.36%). CONCLUSION: There was an increasing trend in the use of symptomatic medications against dementia globally, but the use remained low in LMICs. Interventions may be needed to support the medication use in some countries.

Effect of a novel juvenoid fenoxycarb on the pupal-adult transformation in the blowfly, Chrysomya megacephala (Fabricius, 1794) (Diptera: Calliphoridae).

Chrysomya megacephala (Fabricius, 1794) (Diptera, Calliphoridae) acts as a vector of many disease-causing pathogens. It causes myiasis in human beings and other living vertebrates. In the present study, the effect of a juvenile hormone analog (JHA), fenoxycarb, was evaluated on pupal-adult transformation by exposing pupae (0 and 1-day-old) of blowfly. Pupae were topically treated with different concentrations of the compound, viz., 20, 40, and 80 µg/µl applied on the posterior dorsum with the help of a micropipette. The effects comprised various developmental aberrations, such as delayed pupal-adult ecdysis duration, pupal mortality, formation of pupal-adult intermediates, eclosion failure, reduced adult emergence, and formation of abnormal adults. The freshly molted pupae (0 day) were more susceptible as compared to 1-day-old pupae. Pupal mortality was highest at 80 µg. Normal adult emergence was completely inhibited at day 0 pupae treated with 80 µg of the fenoxycarb. These results demonstrate that fenoxycarb was capable of successfully inhibiting the pupal-adult transformation, and thus, it can be used to control this myiasis-causing agent.

Antipsychotic Initiation Among Older Dementia Patients Using Cholinesterase Inhibitors: A National Retrospective Cohort Study.

BACKGROUND: Evidence regarding the initiation of antipsychotic medications across individual cholinesterase inhibitors (ChEIs) to manage the behavioral symptoms of dementia is lacking. OBJECTIVES: This study compared the risk of initiation of antipsychotic medications among older adults with dementia treated with the ChEIs donepezil, rivastigmine, or galantamine. METHODS: This retrospective cohort study used multiyear (2013-2015) Medicare claims data involving Parts A, B, and D. The study sample included community-dwelling older adults (aged ≥ 65 years) with a diagnosis of dementia. The study identified new users of ChEIs and followed them for up to 180 days for antipsychotic initiation. The ChEIs included donepezil, rivastigmine, and galantamine, whereas antipsychotics included typical and atypical agents. Donepezil was used as the reference category as it is the most commonly used ChEI and only acts on acetylcholinesterase, whereas both rivastigmine and galantamine have dual mechanisms of action. Multivariable Cox proportional hazards regression compared the risk of and time to antipsychotic initiation among the three ChEIs, adjusting for other risk factors. RESULTS: The study cohort consisted of 178,441 older adults with dementia who were new users of ChEIs. A total of 23,433 (15.14%) donepezil users, 4114 (19.04%) rivastigmine users, and 324 (15.77%) galantamine users initiated antipsychotics. The mean time to antipsychotic initiation among patients who received antipsychotics was 109.29 ± 69.72 days for donepezil users, 96.70 ± 71.60 days for rivastigmine users, and 104.15 ± 72.53 days for galantamine users. The Cox regression analysis showed that rivastigmine (adjusted hazard ratio [aHR] = 1.27; 95% confidence interval [CI], 1.20-1.34) was significantly associated with antipsychotic initiation compared with donepezil, whereas no significant difference was observed between galantamine and donepezil (aHR = 0.98; 95% CI, 0.81-1.20). CONCLUSION: The study found a 27% increased risk of antipsychotic initiation among users of rivastigmine compared with donepezil users. There was no difference between galantamine and donepezil for antipsychotic initiation. Although the limitations of the study should be considered, the results suggest that donepezil or galantamine may be more appropriate treatments for older patients with dementia, to minimize antipsychotic use.

Felbamate add-on therapy for drug-resistant focal epilepsy.

BACKGROUND: This is an updated version of the Cochrane Review previously published in 2017.Epilepsy is a chronic and disabling neurological disorder, affecting approximately 1% of the population. Up to 30% of people with epilepsy have seizures that are resistant to currently available antiepileptic drugs and require treatment with multiple antiepileptic drugs in combination. Felbamate is a second-generation antiepileptic drug that can be used as add-on therapy to standard antiepileptic drugs. OBJECTIVES: To evaluate the efficacy and tolerability of felbamate versus placebo when used as an add-on treatment for people with drug-resistant focal-onset epilepsy. SEARCH METHODS: For the latest update we searched the Cochrane Register of Studies (CRS Web), MEDLINE, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP), on 18 December 2018. There were no language or time restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of felbamate and experts in the field for information about any unpublished or ongoing studies. SELECTION CRITERIA: We searched for randomised placebo-controlled add-on studies of people of any age with drug-resistant focal seizures. The studies could be double-blind, single-blind or unblinded and could be of parallel-group or cross-over design. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion and extracted information. In the case of disagreements, the third review author arbitrated. Review authors assessed the following outcomes: 50% or greater reduction in seizure frequency; absolute or percentage reduction in seizure frequency; treatment withdrawal; adverse effects; quality of life. MAIN RESULTS: We included four randomised controlled trials, representing a total of 236 participants, in the review. Two trials had parallel-group design, the third had a two-period cross-over design, and the fourth had a three-period cross-over design. We judged all four studies to be at an unclear risk of bias overall. Bias arose from the incomplete reporting of methodological details, the incomplete and selective reporting of outcome data, and from participants having unstable drug regimens during experimental treatment in one trial. Due to significant methodological heterogeneity, clinical heterogeneity and differences in outcome measures, it was not possible to perform a meta-analysis of the extracted data.Only one study reported the outcome, 50% or greater reduction in seizure frequency, whilst three studies reported percentage reduction in seizure frequency compared to placebo. One study claimed an average seizure reduction of 35.8% with add-on felbamate while another study claimed a more modest reduction of 4.2%. Both studies reported that seizure frequency increased with add-on placebo and that there was a significant difference in seizure reduction between felbamate and placebo (P = 0.0005 and P = 0.018, respectively). The third study reported a 14% reduction in seizure frequency with add-on felbamate but stated that the difference between treatments was not significant. There were conflicting results regarding treatment withdrawal. One study reported a higher treatment withdrawal for placebo-randomised participants, whereas the other three studies reported higher treatment withdrawal rates for felbamate-randomised participants. Notably, the treatment withdrawal rates for felbamate treatment groups across all four studies remained reasonably low (less than 10%), suggesting that felbamate may be well tolerated. Felbamate-randomised participants most commonly withdrew from treatment due to adverse effects. The adverse effects consistently reported by all four studies were: headache, dizziness and nausea. All three adverse effects were reported by 23% to 40% of felbamate-treated participants versus 3% to 15% of placebo-treated participants.We assessed the evidence for all outcomes using GRADE and found it as being very-low certainty, meaning that we have little confidence in the findings reported. We mainly downgraded evidence for imprecision due to the narrative synthesis conducted and the low number of events. We stress that the true effect of felbamate could likely be significantly different from that reported in this current review update. AUTHORS' CONCLUSIONS: In view of the methodological deficiencies, the limited number of included studies and the differences in outcome measures, we have found no reliable evidence to support the use of felbamate as an add-on therapy in people with drug-resistant focal-onset epilepsy. A large-scale, randomised controlled trial conducted over a longer period of time is required to inform clinical practice.

The use of phoxim and bendiocarb for control of fleas in farmed mink (Mustela vison).

BACKGROUND: Fleas (Ceratophyllus sciurorum) are common on farmed mink in Denmark. When present, the fleas have a negative impact on the health of the farmed mink and are of nuisance for farm staff. Severe infestations of fleas cause anemia, poor growth and may result in death of mink kits. Changed behavior of the dams is also observed. Further it has been demonstrated that the fleas are vectors of Aleutian disease virus. Flea control is based on use of a few insecticides and resistance has been reported against permethrin. There is thus a need for new flea control products. In this blinded, randomized clinical trial according to GCP standard, phoxim spray and bendiocarb powder for flea control on mink farms were investigated. RESULTS: Both the phoxim spray solution and bendiocarb powder were found to be efficient for the control of C. sciurorum fleas on farmed mink. Phoxim treatments reduced the number of fleas by 98.4% and the bendiocarb treatments reduced the number of fleas by 99.0% in the mink nest boxes when compared to counts in controls. No clinical signs were observed post treatment. CONCLUSIONS: The study demonstrated that phoxim sprayed on the animals and the use of bendiocarb powder in the nest box material were highly efficient for the control of the C. sciurorum fleas on farmed mink. Both products were safe to use at the recommended dose rate. Both compounds are recommended to be integrated in a new farm management plan suggested here.

Felbamate as an add-on therapy for refractory partial epilepsy.

BACKGROUND: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 7, 2014) on 'Felbamate as an add-on therapy for refractory epilepsy'. Epilepsy is a chronic and disabling neurologic disorder, affecting approximately 1% of the population. Up to 30% of people with epilepsy have seizures that are resistant to currently available drugs. Felbamate is one of the second-generation antiepileptic drugs and we have assessed its effects as an add-on therapy to standard drugs in this review. OBJECTIVES: To evaluate the efficacy and tolerability of felbamate versus placebo when used as an add-on treatment for people with refractory partial-onset epilepsy. SEARCH METHODS: For the latest update we searched the Cochrane Epilepsy Specialized Register, CENTRAL, MEDLINE, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform, up to 20 October 2016. There were no language and time restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of felbamate and experts in the field for information about any unpublished or ongoing studies. SELECTION CRITERIA: Randomised placebo-controlled add-on studies of people of any age with refractory partial-onset seizures. The studies could be double-blind, single-blind or unblinded and could be of parallel or cross-over design. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion and extracted information. We resolved disagreements by discussion. If disagreements persisted, the third review author arbitrated. We assessed the following outcomes: 50% or greater reduction in seizure frequency; absolute or percentage reduction in seizure frequency; treatment withdrawal; adverse effects; quality of life. MAIN RESULTS: We included four randomised controlled trials with a total of 236 participants. Two trials were parallel design, the third had a two-period cross-over design, and the fourth had a three-period cross-over design. Two studies were at an unclear risk of bias for random sequence generation and allocation concealment. These two studies did not include any description of their methods for outcome assessment and performance blinding (i.e. participants or doctors). Two studies were at high risk of bias for incomplete outcome data. Due to significant methodological heterogeneity, clinical heterogeneity and differences in outcome measures, it was not possible to perform a meta-analysis of the results. Only one study reported 50% or greater reduction in seizure frequency. One study reported absolute and percentage reduction in seizure frequency compared to placebo, P values were 0.046 and 0.018, respectively. One study reported percentage reduction in seizure frequency compared to placebo, but there were no P values. Adverse effects rates were higher during the felbamate period than the placebo period, particularly headache, nausea and dizziness. AUTHORS' CONCLUSIONS: In view of the methodological deficiencies, limited number of individual studies and differences in outcome measures, we have found no reliable evidence to support the use of felbamate as an add-on therapy in people with refractory partial-onset epilepsy. A large-scale, randomised controlled trial conducted over a longer period of time is required to inform clinical practice.

Evaluating the safety and efficacy of felbamate in the context of a black box warning: A single center experience.

INTRODUCTION: Felbamate was approved in 1993 to treat partial seizures with and without secondary generalization in adults and in Lennox-Gastaut Syndrome in children. Its use was later restricted when rare but fatal cases of aplastic anemia and hepatic failure were identified. METHODS: This single center analysis retrospectively evaluated the safety and efficacy of felbamate in a cohort of children, adolescents, and adults with epilepsy. RESULTS: A chart review identified 103 patients taking felbamate. The range of felbamate dose was 300-4500 mg (mean: 1800 ± 900 mg). The duration of therapy ranged from 1 month to 20 years (mean duration: 35 ± 45 months). Eighteen (17.5%) subjects experienced adverse events including insomnia, nausea, vomiting, decreased appetite, weight loss, gastric discomfort, diarrhea, mood and behavioral problems, high blood pressure, headache, and elevated liver enzymes. Out of these, 6 (5.9%) patients discontinued the therapy. No hepatic failure or agranulocytosis was observed. Fifty-nine (57.72%) patients achieved ≥ 50% reduction in seizure frequency, and 30 (29.12%) patients achieved seizure freedom. CONCLUSIONS: These findings suggest that felbamate is safe, well tolerated, and effective in treatment of various types of epilepsy syndromes.

[Current approaches to optimize treatment of dementia and Alzheimer's disease]. / Sovremennye podkhody k optimizatsii terapii bolezni Al'tsgeimera.

Currently, substitution therapy is the main focus in the treatment of Alzheimer's disease (AD). It is aimed at overcoming neurotransmitter deficits in a variety of neuronal systems affected in AD. To overcome the cholinergic insufficiency, acetylcholinesterase inhibitors (rivastigmine, donepezil and galantamine) are primarily used. The efficacy and safety of these drugs in AD have been convincingly shown in numerous clinical trials in different countries. Memantine is the main drug in glutamatergic strategies in the treatment of AD, which has a neuroprotective effect and relieves symptoms at the level of the remaining glutamatergic synapses. Some other formulations (cerebrolysin, nicergoline etc) can be also applied as vasoactive and neuroprotective agents.

The rise and fall of felbamate as a treatment for partial epilepsy--aplastic anemia and hepatic failure to blame?

Felbamate has been approved for refractory partial seizures since the early nineties. Due to safety concerns regarding its use, namely, in aplastic anemia and hepatic failure, felbamate's use has been restricted and a 'Black Box' warning has been inserted. Nonetheless, it is a useful drug in refractory cases of partial epilepsy. There are certain precautions which can prevent and minimize the serious idiosyncratic reactions associated with felbamate, thereby providing an option in refractory cases where no other drug works.