Transcranial direct current stimulation (tDCS) in the treatment of depression: Systematic review and meta-analysis of efficacy and tolerability

BACKGROUND Transcranial direct current stimulation (tDCS) is a potential alternative treatment option for major depressive episodes (MDE). OBJECTIVES We address the efficacy and safety of tDCS in MDE. METHODS The outcome measures were Hedges' g for continuous depression ratings, and categorical response and remission rates. RESULTS A random effects model indicated that tDCS was superior to sham tDCS (k=11, N=393, g=0.30, 95% CI=[0.04, 0.57], p=0.027). Adjunctive antidepressant medication and cognitive control training negatively impacted on the treatment effect. The pooled log odds ratios (LOR) for response and remission were positive, but statistically non-significant (response: k=9, LOR=0.36, 95% CI[-0.16, 0.88], p=0.176, remission: k=9, LOR=0.25, 95% CI [-0.42, 0.91], p=0.468). We estimated that for a study to detect the pooled continuous effect (g=0.30) at 80% power (alpha=0.05), a total N of at least 346 would be required (with the total N required to detect the upper and lower bound being 49 and 12,693, respectively). CONCLUSIONS tDCS may be efficacious for treatment of MDE. The data do not support the use of tDCS in treatment-resistant depression, or as an add-on augmentation treatment. Larger studies over longer treatment periods are needed

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

Beyond the DSM: trends in psychiatry diagnoses

Background: Although widely used in clinical practice and research, Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses have low validity: patients with different mental disorders can share similar symptoms, while those with the same diagnosis might have different symptoms. In fact, the DSM diagnostic system has been considered one of the main obstacles for further development of psychiatric research. Recently, it has been proposed that psychiatry nosology should be reframed according to a biologically-based etiology. Objectives: To review present and past endeavors of establishing an etiology-based nosology. Methods: Comprehensive review of articles on the topic. Results: From Hippocrates onwards, multiple attempts have been undertaken aiming to move etiology and nosology closer. The most recent efforts are represented by Developmental Psychopathology (DP) and the Research Domain Criteria (RDoC), which presents an operational matrix recommended to be used in clinical research instead of the DSM diagnoses. Discussion: The DSM-based nosology is faulty. RDoC and DP might be interesting alternatives for an etiology-based nosology. However, while DP has already brought promising results, RDoC is a novel proposal, whose advantages and disadvantages should gradually be identified in the upcoming years

Genetic hearing loss: a study of 228 Brazilian patients

We studied 228 patients, with suspected or confirmed genetic hearing loss, in order to determine the clinical and genetic diagnoses and etiology of each case. Deafness with no associated abnormalities was found in 146 patients (64%) belonging to 112 families. Syndromic deafness was diagnosed in 82 patients (36%) belonging to 76 families. The genetic etiology was as follows: autosomal recessive inheritance in 40.8% of syndromics and non-syndromics, autosomal dominant inheritance in 13.2% and X-linked recessive in 1.3%. In 44.7% of the cases, the etiology of the hearing loss could not be determined. Monogenic causes are the most possible etiology in the latter cases. Parental consanguinity was found in 22.4% of the cases, and deafness was bilateral, profound and neurosensorial in 47.4% of the patients. An early onset of hearing loss (< 2 years of age) occurred in 46.5% of the cases. These results are similar to previous literature reports.Estudamos 228 pacientes, pertencentes a 188 famílias, com deficiência auditiva genética, suspeita ou confirmada, já excluídas causas ambientais, no sentido de determinar o diagnóstico clínico e genético e a etiologia em cada caso, já que estudos deste tipo são escassos em pacientes brasileiros. A surdez sem anomalias associadas compreendeu 146 pacientes (64%) pertencentes a 112 famílias. Deficiência auditiva sindrômica foi diagnosticada em 82 pacientes (36%) pertencentes a 76 famílias. Em 44,7% deles, não foi possível determinar a etiologia da deficiência auditiva e a origem monogênica foi suposta baseada em dados de freqüência. Com relação ao padrão de herança, 40,8%, entre sindrômicos e não-sindrômicos, foram recessivos, 13,2% foram dominantes e 1,3%, ligados ao X. Algumas variáveis foram analisadas: consangüinidade parental foi encontrada em 22,4% dos casos, surdez neurosensorial profunda bilateral em 47,4%, e o início precoce da perda auditiva (até 2 anos) em 46,5%. O estudo clínico e a história familiar revelaram-se como os principais métodos para a definição diagnóstica. As causas genéticas de surdez em pacientes brasileiros são similares aos estudos referidos na literatura.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo (UNIFESP) Departamento de Morfologia Disciplina de GenéticaUNIFESP, Depto. de Morfologia Disciplina de GenéticaSciEL

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