The effect of the interval-between-sessions on prefrontal transcranial direct current stimulation (tDCS) on cognitive outcomes: a systematic review and meta-analysis

Recently, there has been wide interest in the effects of transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) on cognitive functioning. However, many methodological questions remain unanswered. One of them is whether the time interval between active and sham-controlled stimulation sessions, i.e. the interval between sessions (IBS), influences DLPFC tDCS effects on cognitive functioning. Therefore, a systematic review and meta-analysis was performed of experimental studies published in PubMed, Science Direct, and other databases from the first data available to February 2016. Single session sham-controlled within-subject studies reporting the effects of tDCS of the DLPFC on cognitive functioning in healthy controls and neuropsychiatric patients were included. Cognitive tasks were categorized in tasks assessing memory, attention, and executive functioning. Evaluation of 188 trials showed that anodal vs. sham tDCS significantly decreased response times and increased accuracy, and specifically for the executive functioning tasks, in a sample of healthy participants and neuropsychiatric patients (although a slightly different pattern of improvement was found in analyses for both samples separately). The effects of cathodal vs. sham tDCS (45 trials), on the other hand, were not significant. IBS ranged from less than 1 h to up to 1 week (i.e. cathodal tDCS) or 2 weeks (i.e. anodal tDCS). This IBS length had no influence on the estimated effect size when performing a meta-regression of IBS on reaction time and accuracy outcomes in all three cognitive categories, both for anodal and cathodal stimulation. Practical recommendations and limitations of the study are further discussed

Pharmacological and Combined Interventions for the Acute Depressive Episode: Focus on Efficacy and Tolerability

Background: Use of antidepressants is the gold standard therapy for major depression. However, despite the large number of commercially available antidepressant drugs there are several differences among them in efficacy, tolerability, and cost-effectiveness. In addition the optimal augmentation strategy is still not clear when dealing with treatment-resistant depression, a condition that affects 15% to 40% of depressed patients. Methods: We therefore reviewed the main characteristics of these drugs regarding their efficacy, tolerability, side effects and cost-effectiveness, by accessing all meta-analyses and systematic reviews published from 2004 to 2009. In addition, we reviewed the augmentation strategy of associated antidepressants with neurostimulation therapies (such as transcranial magnetic stimulation [TMS] and transcranial direct current stimulation [tDCS]). A search was undertaken in MEDLINE, Web of Science, Cochrane, and Scielo databases. We included: 21 meta-analyses of antidepressant trials, 15 neurostimulation clinical trials and 8 studies of pharmacoeconomics. We then performed a comprehensive review on these articles. Results and Conclusion: Although recent meta-analyses suggest sertraline and escitalopram might have increased efficacy/tolerability, other studies and large pragmatic trials have not found these to be superior to other antidepressant drugs. Also, we did not identify any superior drug in terms of cost-effectiveness due to the different designs observed among pharmacoecomics studies. Side effects such as sexual dysfunction, gastrointestinal problems and weight gain were common causes of discontinuation. Tolerability was an important issue for novel neurostimulation interventions, such as TMS and tDCS. These therapies might be interesting augmentation strategies, considering their benign profile of side effects, if proper safety parameters are adopted

Pharmacological and combined interventions for the acute depressive episode: focus on efficacy and tolerability

Andre R Brunoni1, Renerio Fraguas Jr1, Felipe Fregni21Department and Institute of Psychiatry, University of Sao Paulo, Brazil; 2Laboratory of Neuromodulation, Spaulding Rehabilitation Center, Harvard Medical School and Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USABackground: Use of antidepressants is the gold standard therapy for major depression. However, despite the large number of commercially available antidepressant drugs there are several differences among them in efficacy, tolerability, and cost-effectiveness. In addition the optimal augmentation strategy is still not clear when dealing with treatment-resistant depression, a condition that affects 15% to 40% of depressed patients.Methods: We therefore reviewed the main characteristics of these drugs regarding their efficacy, tolerability, side effects and cost-effectiveness, by accessing all meta-analyses and systematic reviews published from 2004 to 2009. In addition, we reviewed the augmentation strategy of associated antidepressants with neurostimulation therapies (such as transcranial magnetic stimulation [TMS] and transcranial direct current stimulation [tDCS]). A search was undertaken in MEDLINE, Web of Science, Cochrane, and Scielo databases. We included: 21 meta-analyses of antidepressant trials, 15 neurostimulation clinical trials and 8 studies of pharmacoeconomics. We then performed a comprehensive review on these articles.Results and Conclusion: Although recent meta-analyses suggest sertraline and escitalopram might have increased efficacy/tolerability, other studies and large pragmatic trials have not found these to be superior to other antidepressant drugs. Also, we did not identify any superior drug in terms of cost-effectiveness due to the different designs observed among pharmacoecomics studies. Side effects such as sexual dysfunction, gastrointestinal problems and weight gain were common causes of discontinuation. Tolerability was an important issue for novel neurostimulation interventions, such as TMS and tDCS. These therapies might be interesting augmentation strategies, considering their benign profile of side effects, if proper safety parameters are adopted.Keywords: acute depressive episode, pharmacological interventions, combined intervention

Non-invasive brain stimulation therapies

Noninvasive brain stimulation therapies are a promising field for the development of new protocols for the treatment of neuropsychiatric disorders. They are based on the stimulation of neural networks with the intent of modeling their synaptic activity to adequate levels. For this, it is necessary to precisely determine which networks are related to which brain functions, and the normal activation level of each of these networks, so that it is possible to direct the stimulation to the affected networks in order to induce the desired effects. These relationships are under intense investigation by the scientific community, and will contribute to the advancement of treatments by neurostimulation, with the emergence of increasingly accurate and effective protocols for different disorders. Currently, the most used techniques are Transcranial Direct Current Stimulation and Transcranial Magnetic Stimulation, with the most common applications being for treating Major Depressive Disorder. The advancement of research in this field may determine new target networks for stimulation in the treatment of other disorders, extending the application of these techniques and also our knowledge about brain functioning.As terapias biológicas não invasivas se apresentam como um campo promissor para o desenvolvimento de novos protocolos de tratamento de transtornos neuropsiquiátricos. Elas se baseiam na estimulação de redes neurais com intuito de modular sua atividade sináptica para níveis adequados. Para isso, é necessário a determinação precisa de quais redes estão relacionadas a quais funções cerebrais, e do nível de ativação normal de cada uma dessas redes, para que então seja possível direcionar a estimulação às redes afetadas a fim de induzir os efeitos desejados. Essas relações estão sob intensa investigação pela comunidade científica, e vão contribuir para o avanço dos tratamentos por neuroestimulação, com o surgimento de protocolos cada vez mais precisos e efetivos para diferentes transtornos. Atualmente, as técnicas mais utilizadas são a Estimulação Transcraniana por Corrente Contínua e a Estimulação Magnética Transcraniana, sendo a aplicação mais comum no tratamento do Transtorno Depressivo Maior. O avanço das pesquisas possivelmente determinará novas redes alvo para estimulação no tratamento de outros transtornos, estendendo a aplicação dessas técnicas e também do nosso conhecimento sobre o funcionamento cerebral

Evidence-based umbrella review of cognitive effects of prefrontal tDCS

Abstract Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique, which has been increasingly used as an investigational tool in neuroscience. In social and affective neuroscience research, the prefrontal cortex has been primarily targeted, since this brain region is critically involved in complex psychobiological processes subserving both 'hot' and 'cold' domains. Although several studies have suggested that prefrontal tDCS can enhance neuropsychological outcomes, meta-analyses have reported conflicting results. Therefore, we aimed to assess the available evidence by performing an umbrella review of meta-analyses. We evaluated the effects of prefrontal active vs sham tDCS on different domains of cognition among healthy and neuropsychiatric individuals. A MeaSurement Tool to Assess Systematic Reviews 2 was employed to evaluate the quality of meta-analyses, and the GRADE system was employed to grade the quality of evidence of every comparison from each meta-analysis. PubMed/MEDLINE, PsycINFO and the Cochrane Database of Systematic Reviews were searched, and 11 meta-analyses were included resulting in 55 comparisons. Only 16 comparisons reported significant effects favoring tDCS, but 13 of them had either very low or low quality of evidence. Of the remaining 39 comparisons which reported non-significant effects, 38 had either very low or low quality of evidence. Meta-analyses were rated as having critically low and low quality. Among several reasons to explain these findings, the lack of consensus and reproducibility in tDCS research is discussed

tDCS over the left prefrontal cortex enhances cognitive control for positive affective stimuli

Transcranial Direct Current Stimulation (tDCS) is a neuromodulation technique with promising results for enhancing cognitive information processes. So far, however, research has mainly focused on the effects of tDCS on cognitive control operations for non-emotional material. Therefore, our aim was to investigate the effects on cognitive control considering negative versus positive material. For this sham-controlled, within-subjects study, we selected a homogeneous sample of twenty-five healthy participants. By using behavioral measures and event related potentials (ERP) as indexes, we aimed to investigate whether a single session of anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) would have specific effects in enhancing cognitive control for positive and negative valenced stimuli. After tDCS over the left DLPFC (and not sham control stimulation), we observed more negative N450 amplitudes along with faster reaction times when inhibiting a habitual response to happy compared to sad facial expressions. Gender did not influence the effects of tDCS on cognitive control for emotional information. In line with the Valence Theory of side-lateralized activity, this stimulation protocol might have led to a left dominant (relative to right) prefrontal cortical activity, resulting in augmented cognitive control specifically for positive relative to negative stimuli. To verify that tDCS induces effects that are in line with all aspects of the well known Valence Theory, future research should investigate the effects of tDCS over the left vs. right DLPFC on cognitive control for emotional information

Efficacy and acceptability of non-invasive brain stimulation for the treatment of adult unipolar and bipolar depression: A systematic review and meta-analysis of randomised sham-controlled trials

We examined the efficacy and acceptability of non-invasive brain stimulation in adult unipolar and bipolar depression. Randomised sham-controlled trials of transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS) and theta-burst stimulation (TBS), without co-initiation of another treatment, were included. We analysed effects on response, remission, all-cause discontinuation rates and continuous depression severity measures. Fifty-six studies met our criteria for inclusion (N = 3,058, mean age = 44.96 years, 61.73% female). Response rates demonstrated efficacy of high-frequency rTMS over the left DLPFC (OR = 3.75, 95% CI [2.44; 5.75]), right-sided low-frequency rTMS (OR = 7.44, 95%CI [2.06; 26.83]) bilateral rTMS (OR = 3.68,95%CI [1.66; 8.13]), deep TMS (OR = 1.69, 95%CI [1.003; 2.85]), intermittent TBS (OR = 4.70, 95%CI [1.14; 19.38]) and tDCS (OR = 4.17, 95% CI [2.25; 7.74]); but not for continuous TBS, bilateral TBS or synchronised TMS. There were no differences in all-cause discontinuation rates. The strongest evidence was for high-frequency rTMS over the left DLPFC. Intermittent TBS provides an advance in terms of reduced treatment duration. tDCS is a potential treatment for non-treatment resistant depression. To date, there is not sufficient published data available to draw firm conclusions about the efficacy and acceptability of TBS and sTMS