Frederique Van den Eynde

Clinical utility of transcranial direct current stimulation (tDCS) for treating major depression: A systematic review and meta-analysis of randomized, double-blind and sham-controlled trials

OBJECTIVE tDCS is a promising novel therapeutic intervention for major depression (MD). However, clinical trials to date have reported conflicting results concerning its efficacy, which likely resulted from low statistical power. Thus, we carried out a systematic review and meta-analysis on randomized, double-blind and controlled trials of tDCS in MD with a focus on clinically relevant outcomes, namely response and remission rates. METHOD We searched the literature for English language randomized, double-blind and sham-controlled trials (RCTs) on tDCS for treating MD from 1998 through July 2012 using MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials and SCOPUS. We also consulted the Web of Sciences Citations Index Expanded for the selected RCTs up to July 2012. The main outcome measures were response and remission rates. We used a random-effects model and Odds Ratios (OR). RESULTS Data were obtained from 6 RCTs that included a total of 200 subjects with MD. After an average of 10.8 ± 3.76 tDCS sessions, no significant difference was found between active and sham tDCS in terms of both response (23.3% [24/103] vs. 12.4% [12/97], respectively; OR = 1.97; 95% CI = 0.85-4.57; p = 0.11) and remission (12.2% [12/98] vs. 5.4% [5/92], respectively; OR = 2.13; 95% CI = 0.64-7.06; p = 0.22). Also, no differences between mean baseline depression scores and dropout rates in the active and sham tDCS groups were found. Furthermore, sensitivity analyses excluding RCTs that involved less than 10 treatment sessions or stimulus intensity of less than 2 mA did not alter the findings. However, tDCS used as monotherapy was associated with higher response rates when compared to sham tDCS (p = 0.043). Finally, the risk of publication bias in this meta-analysis was found to be low. CONCLUSIONS The clinical utility of tDCS as a treatment for MD remains unclear when clinically relevant outcomes such as response and remission rates are considered. Future studies should include larger and more representative samples, investigate how tDCS compares to other therapeutic neuromodulation techniques, as well as identify optimal stimulation parameters.

Structural magnetic resonance imaging in eating disorders: a systematic review of voxel-based morphometry studies.

This systematic review summarises and critically appraises the literature on structural magnetic resonance imaging in people with a current or past eating disorder. Studies using voxel-based morphometry image analysis were included. Ten studies reported on a total of 236 people with a current or past eating disorder and 257 healthy controls. Sample heterogeneity prohibited a meta-analytic approach. The findings do not unequivocally indicate grey or white matter volume abnormalities in people with an eating disorder. Nevertheless, these preliminary data suggest that, compared with healthy controls, people with anorexia nervosa have decreased grey matter in a range of brain regions and that those with bulimia nervosa have increased grey matter volumes in frontal and ventral striatal areas. Research in the recovery phase and longitudinal studies suggest that potential brain tissue abnormalities may recover with clinical improvement. Overall, as the available data are inconclusive, further efforts in this field are warranted.

Neuroimaging in Eating Disorders and Obesity: Implications for Research

Medicine and psychiatry have benefited from developments in investigational techniques. Neuroimaging is one such domain that has technically progressed enormously in recent years, resulting in, for example, higher temporal and spatial resolution. Neuroimaging techniques have been widely used in a range of psychiatric disorders, providing new insights into neural brain circuits and neuroreceptor functions in vivo. These imaging techniques allow researchers to study not only the configuration of brain structures but also aspects of normal and anomalous human behavior more accurately.

EFFICACY AND ACCEPTABILITY OF HIGH FREQUENCY REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION (rTMS) VERSUS ELECTROCONVULSIVE THERAPY (ECT) FOR MAJOR DEPRESSION: A SYSTEMATIC REVIEW AND META‐ANALYSIS OF RANDOMIZED TRIALS

Clinical trials comparing the efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (HF‐rTMS) and electroconvulsive therapy (ECT) for treating major depression (MD) have yielded conflicting results. As this may have been the result of limited statistical power, we have carried out this meta‐analysis to examine this issue. We searched the literature for randomized trials on head‐to‐head comparisons between HF‐rTMS and ECT from January 1995 through September 2012 using MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, and SCOPUS. The main outcome measures were remission rates, pre‐post changes in depression ratings, as well as overall dropout rates at study end. We used a random‐effects model, Odds Ratios (OR), Number Needed to Treat (NNT), and Hedges’ g effect sizes. Data were obtained from 7 randomized trials, totalling 294 subjects with MD. After an average of 15.2 HF‐rTMS and 8.2 ECT sessions, 33.6% (38/113) and 52% (53/102) of subjects were classified as remitters (OR = 0.46; p = 0.04), respectively. The associated NNT for remission was 6 and favoured ECT. Also, reduction of depressive symptomatology was significantly more pronounced in the ECT group (Hedges’ g = −0.93; p = 0.007). No differences on dropout rates for HF‐rTMS and ECT groups were found. In conclusion, ECT seems to be more effective than HF‐rTMS for treating MD, although they did not differ in terms of dropout rates. Nevertheless, future comparative trials with larger sample sizes and better matching at baseline, longer follow‐ups and more intense stimulation protocols are warranted.

Effectiveness and acceptability of deep brain stimulation (DBS) of the subgenual cingulate cortex for treatment-resistant depression: A systematic review and exploratory meta-analysis

BACKGROUND Deep brain stimulation (DBS) applied to the subgenual cingulate cortex (SCC) has been recently investigated as a potential treatment for severe and chronic treatment-resistant depression (TRD). Given its invasive and experimental nature, a comprehensive evaluation of its effectiveness and acceptability is of paramount importance. Therefore, we conducted the present systematic review and exploratory meta-analysis. METHODS We searched the literature for English language prospective clinical trials on DBS of the SCC for TRD from 1999 through December 2012 using MEDLINE, EMBASE, PsycINFO, CENTRAL and SCOPUS, and performed a random effects exploratory meta-analysis using Event Rates and Hedges׳ g effect sizes. RESULTS Data from 4 observational studies were included, totaling 66 subjects with severe and chronic TRD. Twelve-month response and remission rates following DBS treatment were 39.9% (95% CI=28.4% to 52.8%) and 26.3% (95% CI=13% to 45.9%), respectively. Also, depression scores at 12 months post-DBS were significantly reduced (i.e., pooled Hedges׳ g effect size=-1.89 [95% CI=-2.64 to -1.15, p<0.0001]). Also, there was a significant decrease in depression scores between 3 and 6 months (Hedges׳ g=-0.27, p=0.003), but no significant changes from months 6 to 12. Finally, dropout rates at 12 months were 10.8% (95% CI=4.3% to 24.4%). LIMITATIONS Small number of included studies (most of which were open label), and limited long-term effectiveness data. CONCLUSIONS DBS applied to the SCC seems to be associated with relatively large response and remission rates in the short- and medium- to long-term in patients with severe TRD. Also, its maximal antidepressant effects are mostly observed within the first 6 months after device implantation. Nevertheless, these findings are clearly preliminary and future controlled trials should include larger and more representative samples, and focus on the identification of optimal neuroanatomical sites and stimulation parameters.

Theory of mind in bulimia nervosa

OBJECTIVE This study aimed to investigate theory of mind (ToM) in individuals with bulimia nervosa (BN), an area neglected by empirical research despite social functioning difficulties in this disorder and evidence of ToM deficits in people with anorexia nervosa (AN). METHOD ToM was assessed in 48 BN and 34 Eating Disorder Not Otherwise Specified BN-type (EDNOS-BN) outpatients and 57 healthy controls (HCs) using the Reading the Mind in the Eyes and the Reading the Mind in the Films (RMF), an ecologically valid task novel to BN research. RESULTS Overall performance in BN and EDNOS-BN groups was equivalent to HCs on both tasks. Individuals with BN had enhanced negative emotion recognition on the RMF. DISCUSSION Individuals with AN and BN have distinct socio-cognitive profiles. Further research into social cognition is required to establish the link between interpersonal difficulties and psychopathology in people with BN.

Evaluation of Enhanced Attention to Local Detail in Anorexia Nervosa Using the Embedded Figures Test; an fMRI Study

The behavioural literature in anorexia nervosa and autism spectrum disorders has indicated an overlap in cognitive profiles. One such domain is the enhancement of local processing over global processing. While functional imaging studies of autism spectrum disorder have revealed differential neural patterns compared to controls in response to tests of local versus global processing, no studies have explored such effects in anorexia nervosa. This study uses functional magnetic resonance imaging in conjunction with the embedded figures test, to explore the neural correlates of this enhanced attention to detail in the largest anorexia nervosa cohort to date. On the embedded figures tests participants are required to indicate which of two complex figures contains a simple geometrical shape. The findings indicate that whilst healthy controls showed greater accuracy on the task than people with anorexia nervosa, different brain regions were recruited. Healthy controls showed greater activation in the precuneus whilst people with anorexia nervosa showed greater activation in the fusiform gyrus. This suggests that different cognitive strategies were used to perform the task, i.e. healthy controls demonstrated greater emphasis on visuospatial searching and people with anorexia nervosa employed a more object recognition-based approach. This is in accordance with previous findings in autism spectrum disorder using a similar methodology and has implications for therapies addressing the appropriate adjustment of cognitive strategies in anorexia nervosa.

Blinding success of rTMS applied to the dorsolateral prefrontal cortex in randomised sham-controlled trials: A systematic review

Abstract Objectives. The lack of a suitable sham condition for repetitive transcranial magnetic stimulation (rTMS) research may compromise the success of blinding procedures. The aim of this systematic review was to examine the reporting of blinding success in randomised sham-controlled trials (RCTs) of rTMS applied to the dorsolateral prefrontal cortex. Methods. A literature search using Pubmed and Web of Science was conducted to identify RCTs of rTMS. Regression analyses were used to investigate whether participants in the real and sham rTMS groups differed in (1) their ability to correctly guess to which intervention they had been randomised, and (2) how likely they were to think they had received real rTMS. Results. Thirteen out of 96 (13.5%) RCTs reported blinding success. Available data from 9/13 studies showed that participants in real and sham rTMS groups were not significantly different in their ability to correctly guess their intervention allocation, but with a trend for participants in the real group to more often guess correctly. However, people in the real rTMS groups were significantly more likely to think they had received real rTMS compared with those in sham rTMS groups. Conclusions. Few RCTs in rTMS report on blinding success. As current sham methods may inadequately mimic real rTMS, this could result in only partial success of blinding and bias estimations of treatment effects.

Repetitive Transcranial Magnetic Stimulation over the Dorsolateral Prefrontal Cortex for Treating Posttraumatic Stress Disorder: An Exploratory Meta-Analysis of Randomized, Double-Blind and Sham-Controlled Trials:

Objective: Repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex (DLPFC) has yielded promising results as a treatment for posttraumatic stress disorder (PTSD). However, to date, no quantitative review of its clinical utility has been published. Method: We searched for randomized and sham-controlled trials from 1995 to March 2013 using MEDLINE, Embase, PsycINFO, CENTRAL, and SCOPUS. We then performed an exploratory random effects meta-analysis. Results: Studies on rTMS applied to the right DLPFC included 64 adults with PTSD. The pooled Hedges g effect size for pre and post changes in clinician-rated and self-reported PTSD symptoms were, respectively, 1.65 (P < 0.001) and 1.91 (P < 0.001), indicating significant and large-sized differences in outcome favouring active rTMS. Also, there were significant pre and post decreases with active rTMS in overall anxiety (Hedges g = 1.24; P = 0.02) and depressive (Hedges g = 0.85; P < 0.001) symptoms. Dropout rates at study end did not differ between active and sham rTMS groups. Regarding rTMS applied to the left DLPFC, there is only one study published to date (using a high frequency protocol), and its results showed that active rTMS seems to be superior overall to sham rTMS. Conclusions: Our exploratory meta-analysis shows that active rTMS applied to the DLPFC seems to be effective and acceptable for treating PTSD. However, the small number of subjects included in the analyses limits the generalizability of these findings. Future studies should include larger samples and deliver optimized stimulation parameters.

Effectiveness and acceptability of accelerated repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depressive disorder: An open label trial

BACKGROUND Major depressive disorder (MDD) is a significant cause of worldwide disability and treatment resistance is common. High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has emerged as a treatment for MDD, and while efficacious, the daily commitment for typical 4-6 weeks of treatment poses a significant challenge. We aimed to determine the effectiveness and acceptability of an accelerated rTMS protocol for MDD. METHODS In this naturalistic trial, 27 patients with moderate to severe chronic and treatment-resistant MDD were treated with twice-daily HF-rTMS (10 Hz) applied over the left dorsolateral prefrontal cortex for 2 consecutive weeks (60,000 pulses). The primary outcomes were rates of clinical remission and response (16-item Quick Inventory of Depressive Symptomatology post-treatment score ≤ 6, and ≥ 50% reduction, respectively). Secondary outcomes were self-reported anxious symptoms, depressive symptoms and quality of life, and dropout rates as a proxy for acceptability. RESULTS Ten (37.0%) patients met criteria for clinical remission and 15 (55.6%) were classified as responders, with comparable outcomes for both moderate and severe MDD. Clinician-rated improvements in depressive symptoms were paralleled in self-reported depressive and anxious symptoms, as well as quality of life. No patient discontinued treatment. LIMITATIONS This study is limited by short treatment duration that might be lengthened with corresponding improvements in effectiveness, limited duration of follow-up, small sample size, and an open-label design requiring randomized controlled replication. CONCLUSION An accelerated protocol involving twice-daily sessions of HF-rTMS over the left DLPFC for 2 weeks was effective in treatment-resistant MDD, and had excellent acceptability. Additional research is required to optimize accelerated rTMS treatment protocols and determine efficacy using sham-controlled trials.