Class of 2013 Abstract / Specific Aims: To assess the effectiveness of modafinil as an adjunct agent in the treatment of major depression and depression-related fatigue. Methods Seven databases were searched for articles that met predetermined inclusion criteria and reported sufficient data. Meta-analysis was employed to synthesize study findings, with standardized mean difference (SMD) being the primary summary measure. The I-squared statistic was used to evaluate heterogeneity among studies. Additionally, publication bias was assessed via funnel plots and Kendall’s tau.      Main Results: Ten studies (N = 848) were included in the Hamilton Depression Rating Scale (HAM-D) meta-analysis, composed of 5 RCTs and 5 pre-post studies. The pooled SMD was -0.67, a moderate effect indicating an improvement in depression scores. However, the overall SMD varied when stratified by study design; pre-post studies showed a large pooled effect (SMD = -1.54) that reached significance, whereas RCT's displayed a moderate effect (SMD = -0.41) that was not significant. Additonally, heterogeneity was substantial (I-squared = 91.54) among all studies, and publication bias was suggested by the funnel plot and Kendall's tau. Regarding modafinil and fatigue, the Epworth Sleepiness Scale (ESS) meta-analysis had a small but statistically signficant overall SMD (-0.23; p = 0.03), and the Fatigue Severity Scale (FSS) meta-analysis yielded an overall SMD which was not significant (p = 0.24). Similar to the HAM-D analysis, the overall SMD varied between study designs. Conclusion: The effect of modafinil on major depressive disorder is unclear, as the findings are largely variable and the impact of modafinil was stratified by study design.

In der vorgelegten Studie wurde Modafinil hinsichtlich seiner möglichen antidepressiven und kognitionsverbessernden Wirkung in einem akuten prädiktiven tierexperimentellen Test mit Ratten, dem Forced Swim Test (FST), sowie in einem kognitiven Test zur gerichteten Aufmerksamkeit in der sozialen Diskriminierung (SND), sowie in einem Depressionsmodell der Ratte getestet. Bei der akuten Gabe von Modafinil zeigte sich im FST bei naiven Ratten eine vergleichbare Wirkung mit typischen Antidepressiva, die sich in einer verkürzten immobilen Zeit im Wasserbassin ausdrückte, während durch die akute Administration von Modafinil sich das Diskriminierungsverhalten gesunder Ratten nicht änderte. Zur Induktion depressionsartigen Verhaltens wurde ein 14-tägiges Restrained Stress-Protokoll verwendet. Der FST diente zum Nachweis der depressionsartigen Verhaltensmuster. Gestresste und ungestresste Tiere wurden akut und subchronisch mit Modafinil bzw. Placebo behandelt, um damit die Reversibilität depressionsähnlicher Verhaltensänderungen durch Modafinil zu untersuchen. Das Medikament verbesserte signifikant die depressionsartigen Verhaltensveränderungen und die Aufmerksamkeitsleistung im FST und SND. Mittels Mikrodialyse wurde gezeigt, dass Modafinil die Dopamin-Konzentration im kortikolimbischen System erhöht, so dass dies zu den beobachteten Effekten beitragen könnte. Die vorliegenden Ergebnisse lassen die Schlussfolgerung zu, dass Modafinil antidepressiv-ähnliche und kognitionsverbessernde Wirkungen besitzt und damit eine mögliche Alternative bei der adjuvanten Behandlung menschlicher Depression sein könnte. In weiteren Studien gilt es zu klären, in wie weit die hier gewonnenen Ergebnisse auf die klinische Situation übertragbar sind.

No / Cocrystallization of modafinil, (1), and 1,4-diiodotetrafluorobenzene, (2), in toluene leads to the formation of a metastable modafinil channel hydrate containing an unusual hydrogen bonded dimer motif involving the modafinil molecules that is not seen in anhydrous forms of modafinil. Computational methodologies utilizing bias drift-free differential evolution optimization have been developed and applied to a series of molecular clusters and multicomponent crystals in the modafinil/water and modafinil/water/additive systems for the additive molecules (2) or toluene. These calculations show the channel hydrate is less energetically stable than the anhydrous modafinil but more stable than a cocrystal involving (1) and (2). This provides theoretical evidence for the observed instability of the channel hydrate. The mechanism for formation of the channel hydrate is found to proceed via templating of the modafinil molecules with the planar additive molecules, allowing the formation of the unusual hydrogen-bonded modafinil dimer. It is envisaged that the additive is then replaced by water molecules to form the channel hydrate. The formation of the channel hydrate is more likely in the presence of (2) compared to toluene due to the destabilizing effect of the larger iodine molecules protruding into neighboring modafinil clusters. / Science Foundation Ireland, IRCSET, UCC 2012 Strategic Research Fund

Psychostimulant dependence is a major public health issue in many parts of the world associated with a wide range of psychological, medical and social problems. Psychosocial interventions are the mainstay of treatment for psychostimulant problems, although their effectiveness is compromised by poor uptake and compliance. Despite increasing knowledge of the neurobiological consequences of psychostimulant use, no medications to date have been any more successful than placebo in reducing psychostimulant use in dependent patients. Modafinil is a non-amphetamine type psychostimulant that may have potential as an agonist pharmacotherapy for psychostimulant dependence. The aim of this thesis was to examine the safety, efficacy and cost-effectiveness of modafinil 200 mg/day over ten weeks plus a four session brief CBT intervention for methamphetamine and cocaine dependence through two concurrent randomised placebo controlled trials. There were no statistically significant differences between modafinil and placebo in treatment retention, medication adherence, psychostimulant abstinence, psychostimulant craving or severity of psychostimulant dependence. Methamphetamine-dependent subjects tended to provide more illicit psychostimulant negative urine samples while in treatment than those who received placebo. There appeared to be a reduction in self-reported days of psychostimulant use among methamphetamine-dependent subjects who received modafinil compared to placebo, but the effect size was too small to be statistically significant in this sample. The reduction in self-reported psychostimulant use did reach statistical significance in methamphetamine-dependent subjects with no other substance dependence. Uptake of counselling was the most significant predictor of reduced psychostimulant use post treatment, and the addition of counselling improved the cost-effectiveness of modafinil relative to placebo. Modafinil appeared to be safe, well-tolerated, and non-reinforcing in this treatment population. Compared to placebo, there was a significant increase in weight in subjects who completed the 10-week course of treatment, and a significant decrease in systolic blood pressure in methamphetamine-dependent subjects who received modafinil. The results support further trials of modafinil in methamphetamine-dependent patients, although future trials in cocaine-dependent patients from this treatment population were not likely to be viable. Modafinil appeared to be modestly effective in reducing, but not stopping, methamphetamine use in selected patients. Multi-centre trials with larger sample sizes, and measures sensitive enough to detect quantitative changes in psychostimulant use would be needed to confirm the findings. Blood pressure and weight may be important indicators of clinical outcome, and warrant particular attention in future trials, particularly given the cardio-toxicity of both methamphetamine and cocaine. Strategies to enhance medication adherence including a higher dose and counselling adherence are recommended to improve outcomes. Given the predominance of behavioural and psychosocial factors in psychostimulant dependence, it is likely that the role of medications such as modafinil will be as an adjunct to psychosocial therapy.

Psychostimulant dependence is a major public health issue in many parts of the world associated with a wide range of psychological, medical and social problems. Psychosocial interventions are the mainstay of treatment for psychostimulant problems, although their effectiveness is compromised by poor uptake and compliance. Despite increasing knowledge of the neurobiological consequences of psychostimulant use, no medications to date have been any more successful than placebo in reducing psychostimulant use in dependent patients. Modafinil is a non-amphetamine type psychostimulant that may have potential as an agonist pharmacotherapy for psychostimulant dependence. The aim of this thesis was to examine the safety, efficacy and cost-effectiveness of modafinil 200 mg/day over ten weeks plus a four session brief CBT intervention for methamphetamine and cocaine dependence through two concurrent randomised placebo controlled trials. There were no statistically significant differences between modafinil and placebo in treatment retention, medication adherence, psychostimulant abstinence, psychostimulant craving or severity of psychostimulant dependence. Methamphetamine-dependent subjects tended to provide more illicit psychostimulant negative urine samples while in treatment than those who received placebo. There appeared to be a reduction in self-reported days of psychostimulant use among methamphetamine-dependent subjects who received modafinil compared to placebo, but the effect size was too small to be statistically significant in this sample. The reduction in self-reported psychostimulant use did reach statistical significance in methamphetamine-dependent subjects with no other substance dependence. Uptake of counselling was the most significant predictor of reduced psychostimulant use post treatment, and the addition of counselling improved the cost-effectiveness of modafinil relative to placebo. Modafinil appeared to be safe, well-tolerated, and non-reinforcing in this treatment population. Compared to placebo, there was a significant increase in weight in subjects who completed the 10-week course of treatment, and a significant decrease in systolic blood pressure in methamphetamine-dependent subjects who received modafinil. The results support further trials of modafinil in methamphetamine-dependent patients, although future trials in cocaine-dependent patients from this treatment population were not likely to be viable. Modafinil appeared to be modestly effective in reducing, but not stopping, methamphetamine use in selected patients. Multi-centre trials with larger sample sizes, and measures sensitive enough to detect quantitative changes in psychostimulant use would be needed to confirm the findings. Blood pressure and weight may be important indicators of clinical outcome, and warrant particular attention in future trials, particularly given the cardio-toxicity of both methamphetamine and cocaine. Strategies to enhance medication adherence including a higher dose and counselling adherence are recommended to improve outcomes. Given the predominance of behavioural and psychosocial factors in psychostimulant dependence, it is likely that the role of medications such as modafinil will be as an adjunct to psychosocial therapy.

Made available in DSpace on 2015-07-22T20:50:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-04-28 / Associação Fundo de Incentivo à Psicofarmacologia (AFIP) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A sensibilização comportamental refere-se ao aumento progressivo do efeito estimulante induzido após repetidas administrações de drogas de abuso como cocaína e anfetaminas. Estudos prévios sugerem que o ambiente pareado aos efeitos destas drogas parece ter um importante envolvimento no fenômeno da sensibilização comportamental. Além disso, o tratamento com uma droga de abuso pode interferir com a resposta comportamental eliciada por outra, quando essas possuirem algum mecanismo de ação comum. O presente estudo teve como objetivo investigar o envolvimento da aprendizagem contextual no fenômeno da sensibilização comportamental induzida pelo modafinil e metanfetamina e se haveria uma sensibilização cruzada entre as duas drogas. Os animais foram treinados e testados na tarefa do condicionamento de medo ao contexto (CMC). Após 15 dias foi realizado o teste da novidade, sem nenhuma manipulação farmacológica, às caixas de atividade locomotora. Para avaliar o desenvolvimento da sensibilização comportamental, após 24 horas do teste da novidade grupos diferentes de animais receberam injeções diárias de modafinil (50mg/kg) ou veículo (Experimento 2) e metanfetamina (1mg/kg) ou salina (Experimento 3) via ip por 10 dias e a atividade locomotora foi registrada nos dias 1, 5 e 10. Para avaliar a expressão da sensibilização comportamental, todos os animais foram desafiados com veículo e modafinil (50mg/kg - Experimento 2) e salina e metanfetamina (1mg/kg - Experimento 3) nas caixas de atividade e no campo aberto. No teste de sensibilização cruzada animais pré-tratados com veículo e modafinil receberam uma dose aguda de metanfetamina (Experimento 2) e animais pré-tratados com salina e metanfetamina receberam uma dose aguda de modafinil (Experimento 3). Em ambos os experimentos foi verificado um aumento progressivo na atividade locomotora e uma evidente diferença individual nos níveis de sensibilização comportamental entre os animais tratados com as drogas. Nos experimentos 2 e 3, todos os animais apresentaram resposta similar de tempo de congelamento no teste CMC. A expressão da sensibilização ao modafinil foi observada no ambiente previamente pareado com as administrações e foi bloqueada no ambiente não pareado. No caso da metanfetamina a expressão ocorreu em ambos ambientes. Também foi observado sensibilização cruzada simétrica entre modafinil e metanfetamina. Os resultados do presente estudo apontam para um envolvimento da aprendizagem contextual na sensibilização comportamental, porém parece não ser generalizado para todas as drogas psicoestimulantes. Além disso, apontam que existe uma grande variabilidade individual ao desenvolvimento da sensibilização comportamental ao modafinil e à metanfetamina. Ainda pode-se sugerir que exista um mecanismo similar de ação entre o modafinil e a metanfetamina. / The behavioral sensitization refers to the progressive increase of the stimulatory effect induced by repeated administration of drugs of abuse such as cocaine and amphetamine. Previous studies suggest that the environment paired with the drug stimulant effect of those drugs has an important role in the behavioral sensitization phenomena. Besides, the chronic treatment with one drug of abuse can induce a different patter of response to the administration of other drug indicating that both drug share some similar mechanism of action. The present study aimed to investigate the involvement of contextual learning in the modafinil and methamphetamine behavioral sensitization phenomena and if there is cross-sensitization between the two drugs. Fifteen days after the contextual fear conditioning task, mice received repeated administration of vehicle or modafinil (50mg/kg - Experiment 2) and saline or methamphetamine (1mg/kg - Experiment 3) for 10 days; they were tested in activity cages on days 1, 5 and 10. To evaluate the expression of behavioral sensitization the mice were challenged with vehicle or modafinil (50mg/kg - Experiment 2) and saline or methamphetamine (1 mg/kg - Experiment 3) and then they were tested in the activity cages and in the open field arena. For cross-sensitization test, mice from Experiment 2 were challenged with saline and methamphetamine (1mg/kg) and those mice from Experiment 3 were challenged with vehicle and modafinil (50mg/kg). In both experiments we did not find any correlation between the levels of freezing in the contextual fear conditioning task and different levels of sensitization. Modafinil-sensitized subgroup of mice expressed clear behavioral sensitization in the activity cage, but not in the open field, suggesting a context-dependent expression of modafinil sensitization. We also observed a symmetric cross-sensitization between modafinil and methamphetamine. Our findings indicate that there are a important individual variability to the development of behavioral sensitization to methamphetamine and to modafinil. Besides, we suggest that modafinil and methamphetamine seem to share similar mechanisms of action. / FAPESP: 08/56049-0 / TEDE / BV UNIFESP: Teses e dissertações

In der vorgelegten Studie wurde Modafinil hinsichtlich seiner möglichen antidepressiven und kognitionsverbessernden Wirkung in einem akuten prädiktiven tierexperimentellen Test mit Ratten, dem Forced Swim Test (FST), sowie in einem kognitiven Test zur gerichteten Aufmerksamkeit in der sozialen Diskriminierung (SND), sowie in einem Depressionsmodell der Ratte getestet. Bei der akuten Gabe von Modafinil zeigte sich im FST bei naiven Ratten eine vergleichbare Wirkung mit typischen Antidepressiva, die sich in einer verkürzten immobilen Zeit im Wasserbassin ausdrückte, während durch die akute Administration von Modafinil sich das Diskriminierungsverhalten gesunder Ratten nicht änderte. Zur Induktion depressionsartigen Verhaltens wurde ein 14-tägiges Restrained Stress-Protokoll verwendet. Der FST diente zum Nachweis der depressionsartigen Verhaltensmuster. Gestresste und ungestresste Tiere wurden akut und subchronisch mit Modafinil bzw. Placebo behandelt, um damit die Reversibilität depressionsähnlicher Verhaltensänderungen durch Modafinil zu untersuchen. Das Medikament verbesserte signifikant die depressionsartigen Verhaltensveränderungen und die Aufmerksamkeitsleistung im FST und SND. Mittels Mikrodialyse wurde gezeigt, dass Modafinil die Dopamin-Konzentration im kortikolimbischen System erhöht, so dass dies zu den beobachteten Effekten beitragen könnte. Die vorliegenden Ergebnisse lassen die Schlussfolgerung zu, dass Modafinil antidepressiv-ähnliche und kognitionsverbessernde Wirkungen besitzt und damit eine mögliche Alternative bei der adjuvanten Behandlung menschlicher Depression sein könnte. In weiteren Studien gilt es zu klären, in wie weit die hier gewonnenen Ergebnisse auf die klinische Situation übertragbar sind.

Divers déficits neurocognitifs s'ajoutent à la symptomatologie clinique de la schizophrénie (SZ) et des troubles psychotiques apparentés à la schizophrénie (TPSZ). En plus d'être très prévalents, ils sont maintenant considérés comme des manifestations à part entière de ces psychopathologies. Ceux-ci sont observés au niveau de différentes fonctions attentionelles, mnésiques, et exécutives. Ces déficits revêtent une importance particulière car ils ne sont pas corrigés par les traitements pharmacologiques antipsychotiques, et sont intimement liés au fonctionnement global des gens qui en souffrent. Diverses avenues de traitement sont à l'étude afin de les enrayer, et ultimement, de normaliser le fonctionnement des individus souffrant de SZ ou d'un TPSZ. Cette thèse s'inscrit dans une perspective neuropsychopharmacologique du traitement des déficits cognitifs de la SZ et des TPSZ. Cette thèse doctorale en psychologie comporte cinq chapitres, chacun rédigés de manière à répondre à un objectif particulier. Le chapitre premier a pour visée d'introduire les principales connaIssances relatives aux particularités cliniques, neuropathophysiologiques, et neurocognitives de la SZ et des TPSZ. L'impact fonctionnel des déficits neuropsychologiques y est discuté, puis les objectifs généraux et particuliers de la thèse y sont énoncés. Le deuxième chapitre est pour sa part constitué d'un premier article scientifique dont l'objectif général est de faire état des résultats découlant des premiers essais pharmacologiques visant à traiter les déficits neuropsychologiques dans la SZ et les TPSZ. Le chapitre 3 traite pour sa part, sous le format d'un second article scientifique, des résultats obtenus dans le cadre d'une étude-pilote s'intéressant au modafinil comme adjuvant cognitif potentiel chez des individus souffrant d'une SZ d'apparition récente. Le chapitre 4 est constitué d'un troisième article scientifique. Il a pour objectif la présentation des résultats découlant d'un essai clinique randomisé utilisant le modafinil afin de traiter les déficits neuropsychologiques chez des individus souffrant de SZ ou d'un. TPSZ, et présentant des contre-performances à diverses tâches attentionnelles. Enfin, le chapitre 5 se veut une conclusion générale des résultats des études neuropsychopharmacologiques disponibles dans la littérature, de même que ceux découlant des deux études réalisées dans le cadre de la présente thèse doctorale.

Les traitements pharmacologiques symptomatiques de la maladie d’Alzheimer (MA) actuellement commercialisés ont un effet modeste sur le fonctionnement cognitif. De plus, le développement clinique de nouveaux composés plus efficaces est freiné par l’absence de critères prédictifs pour juger précocement de leur efficacité clinique.Dans ce contexte, l’électroencéphalographie (EEG) pourrait constituer un bio-marqueur suffisamment sensible pour identifier précocement (Phase I) le potentiel thérapeutique d’une nouvelle molécule sur le fonctionnement cognitif. De plus, la difficulté pour détecter des améliorations subtiles dans les performances cognitives en Phase I (i.e. chez des sujets sains) pourrait être palliée par le développement de paradigmes expérimentaux, tels que la privation de sommeil (PS), visant à induire des déficits cognitifs réversibles chez le sujet sain.Ainsi, l’EEG et l’EEG couplée à la privation de sommeil (PS) seraient des stratégies innovantes et pertinentes pour juger et prédire l’efficacité clinique d’une molécule en Phase I.Dans ce travail, nous tentons de juger de la pertinence de telles stratégies en identifiant, chez des sujets sains, des marqueurs EEG du fonctionnement cognitif liés soit (1) à la prise d’un médicament ayant un effet sur la cognition, (2) soit à l’induction d’un déclin cognitif réversible, (3) soit à l’effet concomitant des deux paramètres. Pour y parvenir, deux études ont été réalisées.Dans une première étude, l’effet du donepezil sur l’activité électrique corticale a été étudié chez 30 volontaires adultes, jeunes et sains. Ces volontaires ont été traités par donepezil (5 mg/jour per os) (vs. placebo) pendant 15 jours suivant une procédure en double aveugle, randomisée et en cross-over. _x000D_A la fin de la période de traitement, un EEG (58 voies) a été réalisé au cours de deux tâches attentionnelles (auditive et visuelle). Les potentiels évoqués cognitifs (PEC), la cohérence de phase inter-essais (ITC) et la perturbation spectrale liée à l’événement (ERSP) ont ensuite été calculés.Dans une deuxième étude, l’effet d’une PS a été étudié chez 36 volontaires adultes, jeunes et sains. De plus, l’effet d’un médicament ayant un effet bien connu sur la cognition (en particulier sur la vigilance), le modafinil, a également été étudié sur cette PS.Suite à une PS de 24 h, les participants se sont vus administrés une dose de modafinil (200 mg en prise unique) (vs. placebo) suivant une procédure en double aveugle, randomisée et en cross-over. Un EEG (25 voies) a été réalisé au cours d’une tâche attentionnelle auditive (identique à celle de l’étude I) avant et après la PS. Les PEC, l’ITC et l’ERSP ont ensuite été calculés.Grâce à ces deux études, nous avons identifié, à l’échelle de groupe, des marqueurs EEG de la cognition liés soit à l’induction d’un déclin cognitif (induit par une PS), soit à l’intervention pharmacologique ciblant le système cholinergique (donepezil) ou différents neurotransmetteurs (modafinil). L’ensemble de ces marqueurs porterait sur la modulation de l’activité corticale au sein du réseau fronto-pariétal ventral, connu pour régir les processus attentionnels et exécutifs. Nous avons également confirmé que ce réseau serait sous-tendu par des activités oscillatoires δ/θ et α. L’efficience cognitive serait le reflet de l’intégrité de ce réseau.Nous avons conclu que l’EEG est un outil suffisamment sensible pour détecter des changements subtils dans les processus neurocognitifs de participants adultes, jeunes et sains suivant l’administration d’un traitement de la MA et de manière plus générale suivant l’administration d’un médicament ayant un effet sur la cognition lorsqu’un déclin cognitif est provoqué (PS).Sous réserve de réplication des résultats et d’analyses complémentaires, l’EEG ainsi que l’EEG couplée à la PS pourraient constituer des outils additionnels à l’évaluation cognitive pour prédire l’efficacité de nouveaux candidat médicaments de la MA. / Symptomatic pharmacological treatments currently marketed for Alzheimer’s disease (AD) have a modest effect on cognitive functioning. In addition, the clinical development of new and more effective compounds is hampered by the lack of predictive criteria to judge their early clinical efficacy.In this context, electroencephalography (EEG) could be a sufficiently sensitive biomarker to identify in an early stage (i.e. Phase I) the therapeutic potential of a new molecule on cognitive functioning. In addition, the difficulty to detect subtle improvements in cognitive performance in Phase I (i.e. in healthy subjects) could be overcome by the development of experimental paradigms such as sleep deprivation (SD), to induce cognitive deficits, still reversible in healthy subjects.EEG and EEG coupled with sleep deprivation (SD) would be innovative and relevant strategies to determine and predict the clinical effectiveness of a molecule in Phase I.In this work, we try to determine the relevance of such strategies by identifying, in healthy subjects, EEG markers of cognitive functioning related to (1) either the taking of a cognitive drug, (2) or the induction of a reversible cognitive decline, (3) or concomitant effects of the two parameters. In order to do that, two studies were performed.In a first study, the effect of donepezil on cortical electrical activity was studied in 30 young, healthy adult volunteers. These volunteers were treated with donepezil (5 mg/day orally) (vs. placebo) for 15 days following a double-blind, randomized, cross-over trial.At the end of the treatment period, an EEG (58 electrodes) was performed during two attentional tasks (auditory and visual). Event-related potentials (ERP), the inter-trial coherence (ITC) and the event-related spectral perturbation (ERSP) were then calculated.In a second study, the effect of SD was studied in 36 young, healthy adult volunteers. In addition, the effect of a cognitive drug (involving high alertness), the modafinil was also studied on this SD._x000D_Following a SD of 24 h, the participants were administered a dose of modafinil (200 mg in a single dose) (vs. placebo) in a double-blind, randomized, cross-over trial. An EEG (25 electrodes) was performed in a hearing attentional task (identical to that of Study 1) before and after the PS. The ERP, ITC and ERSP were then calculated.Through these two studies, we have found, at the group level, cognitive EEG markers related either to the induction of cognitive decline (SD) or pharmacological intervention targeting cholinergic system (donepezil) or several neurotransmitters (modafinil). All these markers would concern the modulation of cortical activity in the ventral frontoparietal network, known to regulate attentional and executive processes. We also confirmed that the network is underlying by δ/θ and α oscillatory activities. The cognitive efficiency would reflect the integrity of the network.We conclude that EEG is a sufficiently sensitive tool to detect subtle changes in neurocognitive processes of young, healthy adult volunteers, following the administration of a treatment of AD and more generally following the administration of a drug having an effect on cognition when cognitive decline is caused (SD).EEG and EEG coupled with SD could constitute additional tools to the current cognitive assessment for predicting the efficacy of new drug candidates for AD before initiation Phases II/III clinical trials. However, the present works needs to be replicated so that the EEG markers described here can be validated so as to be used in drug trials.

The Side Effects of Drugs Annuals forms a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. The purpose of this supplement is to provide a concise reference of the newly available literature to support the existing information regarding the known adverse effects of commonly prescribed medications or abused drugs. The information covers peer-reviewed publications from January 2016 to December 2016. This review focused on CNS stimulants and drugs that suppress appetite. It covers amphetamines (including lisdexamfetamine, methamphetamine and 3,4-methylenedioxymetamphetamine), methylphenidate, atomoxetine, modafinil and armodafinil, methylxanthines (caffeine), monotherapies and combinational therapies that suppress appetite (lorcaserin, phentermine, phentermine/topiramate) and medications used in Alzheimer's disease and cognitive decline (rivastigmine, donepezil and memantine).