Left to Their Own Devices: Breakdowns in United States Medical Device Premarket Review

Using examples from recent FDA regulatory proceedings, Jonas Hines and colleagues critique the medical device premarket review and identify eight weaknesses in the process that should be remedied

Meta-Review of Metanalytic Studies with Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Major Depression

BACKGROUND: Major Depression (MD) and treatment-resistant depression (TRD) are worldwide leading causes of disability and therapeutic strategies for these impairing and prevalent conditions include pharmacological augmentation strategies and brain stimulation techniques. In this perspective, repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique with a favorable profile of tolerability which, despite being recently approved by the Food and Drug Administration (FDA) for the treatment of patients with medication-refractory unipolar depression, still raises some doubts about most effective parameters of stimulation.METHODS: A literature search was performed using PubMed for the years 2001 through February 2011 in order to review meta-analytic studies assessing efficacy and safety issues for rTMS in depressive disorders. Fifteen meta-analyses were identified and critically discussed in order to provide an updated and comprehensive overview of the topic with specific emphasis on potentially optimal parameters of stimulation.RESULTS: First meta-analyses on the efficacy of rTMS for the treatment of MD and TRD have shown mixed results. On the other hand, more recent meta-analytic studies seem to support the antidepressant efficacy of the technique to a greater extent, also in light of longer periods of stimulation (e.g. > 2 weeks).CONCLUSION: rTMS seems to be an effective and safe brain stimulation technique for the treatment of medication refractory depression. Nevertheless, further studies are needed to better define specific stimulation-related issues, such as duration of treatment as well as durability of effects and predictors of response

rTMS of the Left Dorsolateral Prefrontal Cortex Modulates Dopamine Release in the Ipsilateral Anterior Cingulate Cortex and Orbitofrontal Cortex

Background: Brain dopamine is implicated in the regulation of movement, attention, reward and learning and plays an important role in Parkinson’s disease, schizophrenia and drug addiction. Animal experiments have demonstrated that brain stimulation is able to induce significant dopaminergic changes in extrastriatal areas. Given the up-growing interest of noninvasive brain stimulation as potential tool for treatment of neurological and psychiatric disorders, it would be critical to investigate dopaminergic functional interactions in the prefrontal cortex and more in particular the effect of dorsolateral prefrontal cortex (DLPFC) (areas 9/46) stimulation on prefrontal dopamine (DA). Methodology/Principal Findings: Healthy volunteers were studied with a high-affinity DA D2-receptor radioligand, [ 11 C]FLB 457-PET following 10 Hz repetitive transcranial magnetic stimulation (rTMS) of the left and right DLPFC. rTMS on the left DLPFC induced a significant reduction in [ 11 C]FLB 457 binding potential (BP) in the ipsilateral subgenual anterior cingulate cortex (ACC) (BA 25/12), pregenual ACC (BA 32) and medial orbitofrontal cortex (BA 11). There were no significant changes in [ 11 C]FLB 457 BP following right DLPFC rTMS. Conclusions/Significance: To our knowledge, this is the first study to provide evidence of extrastriatal DA modulation following acute rTMS of DLPFC with its effect limited to the specific areas of medial prefrontal cortex. [ 11 C]FLB 457-PET combined with rTMS may allow to explore the neurochemical functions of specific cortical neural networks and help t

Placebo Response of Non-Pharmacological and Pharmacological Trials in Major Depression: A Systematic Review and Meta-Analysis

Background: Although meta-analyses have shown that placebo responses are large in Major Depressive Disorder (MDD) trials; the placebo response of devices such as repetitive transcranial magnetic stimulation (rTMS) has not been systematically assessed. We proposed to assess placebo responses in two categories of MDD trials: pharmacological (antidepressant drugs) and non-pharmacological (device- rTMS) trials. Methodology/Principal Findings: We performed a systematic review and meta-analysis of the literature from April 2002 to April 2008, searching MEDLINE, Cochrane, Scielo and CRISP electronic databases and reference lists from retrieved studies and conference abstracts. We used the keywords placebo and depression and escitalopram for pharmacological studies; and transcranial magnetic stimulation and depression and sham for non-pharmacological studies. All randomized, double-blinded, placebo-controlled, parallel articles on major depressive disorder were included. Forty-one studies met our inclusion criteria - 29 in the rTMS arm and 12 in the escitalopram arm. We extracted the mean and standard values of depression scores in the placebo group of each study. Then, we calculated the pooled effect size for escitalopram and rTMS arm separately, using Cohen's d as the measure of effect size. We found that placebo response are large for both escitalopram (Cohen's d - random-effects model - 1.48; 95%C.I. 1.26 to 1.6) and rTMS studies (0.82; 95%C.I. 0.63 to 1). Exploratory analyses show that sham response is associated with refractoriness and with the use of rTMS as an add-on therapy, but not with age, gender and sham method utilized. Conclusions/Significance: We confirmed that placebo response in MDD is large regardless of the intervention and is associated with depression refractoriness and treatment combination (add-on rTMS studies). The magnitude of the placebo response seems to be related with study population and study design rather than the intervention itself

Neurostimulatory and ablative treatment options in major depressive disorder: a systematic review

Introduction Major depressive disorder is one of the most disabling and common diagnoses amongst psychiatric disorders, with a current worldwide prevalence of 5-10% of the general population and up to 20-25% for the lifetime period. Historical perspective Nowadays, conventional treatment includes psychotherapy and pharmacotherapy; however, more than 60% of the treated patients respond unsatisfactorily, and almost one fifth becomes refractory to these therapies at long-term follow-up. Nonpharmacological techniques Growing social incapacity and economic burdens make the medical community strive for better therapies, with fewer complications. Various nonpharmacological techniques like electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation, lesion surgery, and deep brain stimulation have been developed for this purpose. Discussion We reviewed the literature from the beginning of the twentieth century until July 2009 and described the early clinical effects and main reported complications of these methods. © The Author(s) 2010.Link_to_subscribed_fulltex

Síndrome do comer noturno: aspectos conceituais, epidemiológicos, diagnósticos e terapêuticos Night eating syndrome: conceptual, epidemiological, diagnostic and therapeutic aspects

O comportamento e o padrão alimentar são complexos, envolvendo aspectos metabólicos, fisiológicos e ambientais, e apresentando ritmicidade circadiana, herdada e espécie específica, sendo a humana essencialmente diurna. Este estudo tem como objetivo descrever a Síndrome do Comer Noturno, caracterizada por um atraso circadiano do padrão alimentar, mediado por alterações neuroendócrinas ao estresse. Procedeu-se à revisão da bibliografia existente, a partir do exame de artigos publicados pela literatura internacional nas bases de dados dos sites Pubmed, Lilacs, Sirus, referentes ao período de 1955 até as últimas publicações em 2007. Realizou-se um levantamento bibliográfico usando os seguintes descritores: night eating syndrome, sleep, circadian rhythm, appetite, nocturnal eating. Foram localizados 74 artigos e destes foram selecionados 26, cujo tema central era a Síndrome do Comer Noturno. Apesar dos estudos realizados, ainda existe longo percurso a ser percorrido para compreender a gênese da Síndrome do Comer Noturno e as relações intrínsecas desta com outros processos fisiopatogênicos. Tendo em conta que esta síndrome está vinculada ao controle da fome e da saciedade e à dessincronização entre o ritmo alimentar e o ritmo sono/vigília, a compreensão do seu processo gênico poderá demonstrar o impacto da dessincronização dos ritmos circadianos da alimentação no processo saúde-doença, e auxiliar a compreensão de fatores implicados no índice crescente de obesidade da sociedade moderna.<br>Behavior and eating patterns are complex, involve metabolic, physiological and environmental aspects and have inherited and species-specific circadian rhythmicity, with humans being essentially diurnal. The aim of this study is to describe the night eating syndrome, characterized by a delay of the circadian eating patterns and mediated by neuroendocrine stress. A review of the literature found in the Pubmed, Lilacs and Sirus databases published between 1955 and 2007 was done. The keywords used were: night eating syndrome, sleep, circadian rhythm, appetite, nocturnal eating. A total of 74 articles were found of which 26 were selected, whose central theme was the night eating syndrome. Despite all the studies done, there is still long way to go to understand the genesis of the night eating syndrome and its intrinsic relation with other physiological and pathogenic processes. Given that this syndrome is linked to the control of hunger and satiety and to the desynchronization between the eating rhythm and sleep / wake rhythm, understanding its genetic process can reveal the impact that the desynchronization of circadian eating rhythms has on the health-disease process and help understand the factors involved in the rising rates of obesity in modern society