A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression

Preliminary findings suggest that transcranial direct current stimulation (tDCS) can have antidepressant effects. We sought to test this further in a parallel-group, double-blind clinical trial with 40 patients with major depression, medication-free randomized into three groups of treatment: anodal tDCS of the left dorsolateral prefrontal cortex (active group - 'DLPFC'); anodal tDCS of the occipital cortex (active control group - 'occipital') and sham tDCS (placebo control group - 'sham'). tDCS was applied for 10 sessions during a 2-wk period. Mood was evaluated by a blinded rater using the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). The treatment was well tolerated with minimal side-effects that were distributed equally across all treatment groups. We found significantly larger reductions in depression scores after DLPFC tDCS [HDRS reduction of 40.4% (+/-25.8%)] compared to occipital [HDRS reduction of 21.3% (+/-12.9%)] and sham tDCS [HDRS reduction of 10.4% (+/-36.6%)]. The beneficial effects of tDCS in the DLPFC group persisted for 1 month after the end of treatment. Our findings support further investigation on the effects of this novel potential therapeutic approach - tDCS - for the treatment of major depression.     

Antidepressant effects of different schedules of repetitive transcranial magnetic stimulation vs. clomipramine in patients with major depression: relationship to changes in cortical excitability

The antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) that have been demonstrated in recent studies could be related to its ability to modulate cortical excitability. Yet, the relationship between stimulus location and frequency and treatment outcome has not been established. The aim of the present study was to compare efficacy of rTMS in various configurations and clomipramine treatment in patients with major depression (MD) and to evaluate the relationship between clinical outcome and changes in cortical excitability. Fifty-nine MD patients were randomized to receive (1) left (n = 12) or right (n = 12) 3 Hz rTMS with placebo medication; (2) left (n = 10) or right (n = 9) 10 Hz rTMS with placebo medication; (3) active medication (clomipramine) with sham rTMS (n = 16). Both 3 Hz and 10 Hz rTMS were administered to the prefrontal cortex by a circular coil at an intensity of 110% and 100% of the resting motor threshold (rMT) respectively. Measurements of cortical excitability were performed prior to and 24 h after completion of 2 wk of daily rTMS or pharmacological treatments. These included the rMT, silent period threshold (SPT), inter-threshold difference (ITD), MEP/M-wave amplitude ratio and silent period duration (SPD). Severity of depression was blindly assessed by the Hamilton Depression Rating Scale (HDRS). The best improvement scores were seen in patients who received left 3 Hz rTMS. The 10 Hz rTMS treatment was less tolerated resulting in a significantly higher dropout rate. A significant increase of the MEP/M wave amplitude ratio accompanied by a shortening of the SPD was evidenced in patients who showed marked clinical improvement (reduction in HDRS by 50% or more) following left rTMS regardless of stimulation frequency. Our results suggest that 3 Hz left rTMS has a higher therapeutic efficacy and tolerability in patients with MD. The enhancement of cortical excitability may be related to the antidepressant action of rTMS.     

Low frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex transiently increases cue-induced craving for methamphetamine: A preliminary study

Background

Repetitive transcranial magnetic stimulation (rTMS) can temporarily interrupt or facilitate activity in a focal brain region. Several lines of evidence suggest that rTMS of the dorsolateral prefrontal cortex (DLPFC) can affect processes involved in drug addiction. We hypothesized that a single session of low-frequency rTMS of the left DLPFC would modulate cue-induced craving for methamphetamine (MA) when compared to a sham rTMS session.

Methods

In this single-blind, sham-controlled crossover study, 10 non-treatment seeking MA-dependent users and 8 healthy controls were randomized to receive 15 min of sham and real (1 Hz) DLPFC rTMS in two experimental sessions separated by 1 h. During each rTMS session, participants were exposed to blocks of neutral cues and MA-associated cues. Participants rated their craving after each cue block.

Results

In MA users, real rTMS over the left DLPFC increased self-reported craving as compared to sham stimulation (17.86 ± 1.46 vs. 24.85 ± 1.57, p = 0.001). rTMS had no effect on craving in healthy controls. One Hertz rTMS of the left DLPFC was safe and tolerable for all participants.

Conclusions

Low frequency rTMS of the left DLPFC transiently increased cue-induced craving in MA participants. These preliminary results suggest that 1 Hz rTMS of the left DLPFC may increase craving by inhibiting the prefrontal cortex or indirectly activating subcortical regions involved in craving.     

Repetitive transcranial magnetic stimulation (rTMS) in major depression: relation between efficacy and stimulation intensity.

Repetitive transcranial magnetic stimulation (rTMS) has been found to exert modest to substantial antidepressant effects in the majority of prior clinical studies. As effect sizes and stimulation conditions have varied greatly, controversy persists regarding effective stimulation parameters (e.g. intensity, frequency, localization). In the present controlled study, we investigated whether the antidepressant efficacy of rTMS may be related to the stimulation intensity applied. Thirty-one patients suffering from a pharmacotherapy-resistant major depressive episode were randomly assigned to three treatment groups receiving rTMS at different stimulation intensities: (1) intensity at the individual motor threshold (MT); (2) 90% subthreshold intensity; and (3) low intensity of standard sham rTMS. Each patient underwent 10 sessions of 10 Hz rTMS with 1500 stimuli/day over the left dorsolateral prefrontal cortex. Improvement of depressive symptoms after rTMS significantly increased with stimulation intensity across the three groups. A 30% to 33% reduction of baseline depression scores was observed after rTMS at MT intensity. Similarly, groups differed significantly regarding the clinical course after rTMS with the lowest number of antidepressant interventions and the shortest hospital stay in the MT intensity group. These findings support the hypothesis of a relationship between stimulation intensity of rTMS and its antidepressant efficacy.     

The efficacy of selective serotonin re-uptake inhibitors in depression: a meta-analysis of studies against tricyclic antidepressants

A meta-analysis of the efficacy of five selective serotonin re-uptake inhibitors (SSRIs) against non-selective and noradrenergic re-uptake inhibitors (mainly tricyclic antidepressants, TCAs) is presented. Fifty five double- blind studies were identified after excluding those multiply reported or with methodological problems likely to bias the outcome in favour of SSRIs. Standardised effect sizes and 95% confidence intervals were calculated based on the difference in the reduction in mean Hamilton depression rating scale (HDRS) scores for the two antidepressants. For studies not reporting standard deviations, the pooled variance from complete studies was used and a variance-weighted mean effect size calculated. There were no differences in efficacy between SSRIs and comparator antidepressants for SSRIs taken together or individually. If studies were classified into high and low depression scores based on a median split of initial HDRS scores, there was a slight advantage to TCAs in the high HDRS group. In addition, SSRIs were slightly less effective than TCAs in in-patients and against combined serotonin and noradrenaline re-uptake inhibitors (clomipramine and amitriptyline). These findings were accounted for by a clinically significant lower efficacy of paroxetine in these subgroups. In contrast, SSRIs as a group were marginally more effective than noradrenergic antidepressants, a finding accounted for by two studies with sertraline. Fluvoxamine was the only SSRI to have been tested adequately in in-patients, where it displayed equal efficacy to TCAs. This meta-analysis confirms that SSRIs and TCAs are in general equally effective, but suggests that paroxetine's efficacy in in-patients and against clomipramine and amitriptyline is not proven.     

rTMS treatment for depression in Parkinson's disease increases BOLD responses in the left prefrontal cortex

The mechanisms underlying the effects of antidepressant treatment in patients with Parkinson's disease (PD) are unclear. The neural changes after successful therapy investigated by neuroimaging methods can give insights into the mechanisms of action related to a specific treatment choice. To study the mechanisms of neural modulation of repetitive transcranial magnetic stimulation (rTMS) and fluoxetine, 21 PD depressed patients were randomized into only two active treatment groups for 4 wk: active rTMS over left dorsolateral prefrontal cortex (DLPFC) (5 Hz rTMS; 120% motor threshold) with placebo pill and sham rTMS with fluoxetine 20 mg/d. Event-related functional magnetic resonance imaging (fMRI) with emotional stimuli was performed before and after treatment - in two sessions (test and re-test) at each time-point. The two groups of treatment had a significant, similar mood improvement. After rTMS treatment, there were brain activity decreases in left fusiform gyrus, cerebellum and right DLPFC and brain activity increases in left DLPFC and anterior cingulate gyrus compared to baseline. In contrast, after fluoxetine treatment, there were brain activity increases in right premotor and right medial prefrontal cortex. There was a significant interaction effect between groups vs. time in the left medial prefrontal cortex, suggesting that the activity in this area changed differently in the two treatment groups. Our findings show that antidepressant effects of rTMS and fluoxetine in PD are associated with changes in different areas of the depression-related neural network.     

Comparison of unlimited numbers of rapid transcranial magnetic stimulation (rTMS) and ECT treatment sessions in major depressive episode

Repetitive transcranial magnetic stimulation (rTMS) is a new technology which holds promise as a treatment of psychiatric disorders. Most work to date has been on depression. Superiority to placebo has been indicated in three small blind studies. We compared the antidepressant effects of rTMS and ECT in 32 patients suffering major depressive episode (MDE) who had failed to respond to at least one course of medication. There was no limit to the number of treatment sessions which could be given and treatment was continued until remission occurred or response plateaued. A significant main effect for treatment type was found [Pillai trace = 0.248, F(3,28) = 3.076, p = 0.044; power = 0.656], reflecting an advantage for ECT patients on measures of depression overall, however, rTMS produced comparable results on a number of measures. Blind raters using the 17-item Hamilton Depression Rating Scale (HDRS) found the rate of remission (HDRS = ? 8) was the same (68.8%), and the percentage improvement over the course of treatment of 55.6% (rTMS) and 66.4% (ECT), while favouring ECT, was not significantly different. Significant differences were shown (p & 0.03) in percentage improvement on Beck Depression Inventory ratings (rTMS, 45.5%; ECT, 69.1%), but not for improvement in Visual Analogue ratings of mood (rTMS 42.3%; ECT, 57%). rTMS has antidepressant effects of useful proportions and further studies are indicated.     

Partial clinical response to 2 weeks of 2 Hz repetitive transcranial magnetic stimulation to the right parietal cortex in depression

The aim of this treatment study was to evaluate the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) over the right parietal cortex in depression. In a double-blind, sham-controlled design ten consecutive sessions of 2 Hz rTMS (inter-pulse interval 0.5 s) at 90% motor threshold to the right parietal cortex (2400 pulses per session) were applied to 34 patients with the primary diagnosis of DSM-IV depression and a score of > or =15 on the 17-item Hamilton Rating Scale for Depression (HAMD). The primary outcome measures were the percentage change from baseline on the 17-item HAMD scores after ten sessions, and the percentage of clinical (defined as > or =50% reduction in HAMD score) and partial clinical (defined as > or =30% reduction in HAMD score) responders. Reduction of HAMD scores in the real rTMS treatment (mean real+/-S.D., -19.9+/-32.5%) was not statistically different from the sham rTMS treatment (mean sham+/-S.D., -5.6+/-28.4%), and the number of clinical responders did not differ between treatments. However, a significant greater number of partial clinical responders were observed in the real (43.8%) compared to the sham rTMS treatment (6.3%). This study provides the first evidence showing that 2 Hz rTMS over the right parietal cortex may have antidepressant properties, and warrants further research.     

One session of high frequency repetitive transcranial magnetic stimulation (rTMS) to the right prefrontal cortex transiently reduces cocaine craving

BACKGROUND: Cocaine dependence is a public health problem affecting 2 million individuals in USA. Craving is a predictor of subsequent cocaine use and is related to changes in brain activity in networks involving the prefrontal cortex. METHODS: We investigated the efficacy of one session of high frequency repetitive transcranial magnetic stimulation (rTMS) to reduce craving in cocaine addicted subjects. Six patients underwent two sessions of 10Hz rTMS over left or right dorsolateral prefrontal cortex (DLPFC). Before, immediately after and 4h after rTMS we measured craving using visual analogue scales. RESULTS: Right, but not left, DLPFC stimulation significantly reduced craving over time (F(2,10)=11.07, p=0.0029). The reduction was 19% (13.4-24.6%) from baseline and disappeared after 4h. The interaction of time by site of stimulation for craving was also significant (F(2,25)=6.13, p=0.0068). CONCLUSION: One session of 10Hz rTMS over right, but not left, DLPFC transiently reduces craving in cocaine dependent individuals. These results highlight the potential of non-invasive neuromodulation as a therapeutic tool for cocaine addiction.     

Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: a double-blind, sham-controlled study

BACKGROUND: Functional neuroimaging studies have shown that specific brain areas are associated with alcohol craving including the dorsolateral prefrontal cortex (DLPFC). We tested whether modulation of DLPFC using transcranial direct current stimulation (tDCS) could alter alcohol craving in patients with alcohol dependence while being exposed to alcohol cues. METHODS: We performed a randomized sham-controlled study in which 13 subjects received sham and active bilateral tDCS delivered to DLPFC (anodal left/cathodal right and anodal right/cathodal left). For sham stimulation, the electrodes were placed at the same positions as in active stimulation; however, the stimulator was turned off after 30s of stimulation. Subjects were presented videos depicting alcohol consumption to increase alcohol craving. RESULTS: Our results showed that both anodal left/cathodal right and anodal right/cathodal left significantly decreased alcohol craving compared to sham stimulation (p<0.0001). In addition, we found that following treatment, craving could not be further increased by alcohol cues. CONCLUSIONS: Our findings showed that tDCS treatment to DLPFC can reduce alcohol craving. These findings extend the results of previous studies using noninvasive brain stimulation to reduce craving in humans. Given the relatively rapid suppressive effect of tDCS and the highly fluctuating nature of alcohol craving, this technique may prove to be a valuable treatment strategy within the clinical setting.     

Neuromodulation of delay discounting,the reflection effect,and cigarette consumption

Cigarette smokers and substance users discount the value of delayed outcomes more steeply than non-users. Higher discounting rates are associated with relapse and poorer treatment outcomes. The left dorsolateral prefontal cortex (DLPFC) exerts an inhibitory influence on impulsive or seductive choices. Greater activity in the prefrontal cortex is associated with lower discounting rates. We hypothesized that increasing activity in the left DLPFC with high frequency repetitive transcranial magnetic stimulation (HF rTMS) would decrease delay discounting and decrease impulsive decision-making in a gambling task as well as decrease cigarette consumption, similar to other studies. In this single-blind, within-subjects design, smokers with no intention to quit (n = 47) and nonsmokers (n = 19) underwent three counterbalanced sessions of HF rTMS (20 Hz, 10 Hz, sham) delivered over the left DLPFC. Tasks were administered at baseline and after each stimulation session. Stimulation decreased discounting of monetary gains (F_[3,250] = 4.46, p < .01), but increased discounting of monetary losses (F_[3,246] = 4.30, p < .01), producing a reflection effect, normally absent in delay discounting. Stimulation had no effect on cigarette consumption. These findings provide new insights into cognitive processes involved with decision-making and cigarette consumption and suggest that like all medications for substance dependence, HF rTMS is likely to be most effective when paired with cognitive–behavioral interventions.     

Priming stimulation enhances the effectiveness of low-frequency right prefrontal cortex transcranial magnetic stimulation in major depression

OBJECTIVES: Low-frequency, right-sided repetitive transcranial magnetic stimulation (rTMS) to the prefrontal cortex has been shown to have antidepressant effects. Recent research has suggested that preceding low-frequency rTMS with a period of low-intensity, 6-Hz stimulation ("priming") enhances the physiological effects of low-frequency stimulation. The aim of this study was to investigate whether priming stimulation would enhance therapeutic response to low-frequency rTMS in patients with depression. METHOD: The study consisted of a 2-arm, double-blind, randomized, controlled trial in 60 patients with treatment-resistant depression. Right 1-Hz rTMS was provided in one continuous, 15-minute train to all subjects. The priming stimulation (twenty 5-second, 6-Hz trains) or an equivalent, sham preceded 1-Hz stimulation. The primary outcome variable was the score on the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: There was a significant overall reduction in MADRS scores across the 4 weeks of the study and a significantly greater reduction in MADRS scores in the active-priming group compared with the sham-priming group. CONCLUSIONS: Low-intensity, high-frequency priming stimulation appears to enhance the response to low-frequency, right-sided rTMS treatment in patients with treatment-resistant depression.     

Low frequency daily left prefrontal rTMS improves mood in bipolar depression: a placebo-controlled case report

Preliminary studies in unipolar depression indicate that daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) reduces symptoms of depression. rTMS treatment of depression occurring in the setting of bipolar disorder has been less well studied. To assess the efficacy and toxicity of rTMS in the depressed phase of bipolar disorder, we treated a man with bipolar disorder who was known to develop hypomania and mania with conventional antidepressants. A 47 year old man with Bipolar Disorder type 1, depressed phase, was entered into a double-blind parallel treatment trial of left prefrontal rTMS. He was randomized to receive left prefrontal rTMS at low frequency (5 Hz) for 2 weeks, which was then followed by an open phase. The patient's Hamilton Depression scores decreased 44 per cent across the first 2 weeks. In an open extension, his mood further improved over another 2 weeks and he was gradually tapered from rTMS treatments. He had no side effects. Importantly, he did not develop mania, as had occurred with all prior antidepressant trials. After several months he experienced a recurrence of depressive symptoms, was retreated, and re-responded. Further studies are warranted to investigate the optimum dose, duration, location and frequency of rTMS treatments for the depressed phase of bipolar disorder. © 1998 John Wiley & Sons, Ltd.     

A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression

Several clinical studies on major depressive disorder (MDD) have shown that blood brain-derived neurotrophic factor (BDNF) - a factor used to index neuroplasticity - is associated with depression response; however, the results are mixed. The purpose of our study was to evaluate whether BDNF levels are correlated with improvement of depression. We performed a systematic review and meta-analysis of the literature, searching Medline, Cochrane Central, SciELO databases and reference lists from retrieved articles for clinical studies comparing mean BDNF blood levels in depressed patients pre- and post-antidepressant treatments or comparing depressed patients with healthy controls. Two reviewers independently searched for eligible studies and extracted outcome data using a structured form previously elaborated. Twenty articles, including 1504 subjects, met our inclusion criteria. The results showed that BDNF levels increased significantly after antidepressant treatment (effect size 0.62, 95% CI 0.36-0.88, random effects model). In addition, there was a significant correlation between changes in BDNF level and depression scores changes (p=0.02). Moreover, the results were robust according to the sensitivity analysis and Begg's funnel plot results did not suggest publication bias. Finally, there was a difference between pre-treatment patients and healthy controls (effect size 0.91, 95% CI 0.70-1.11) and a small but significant difference between treated patients and healthy controls (effect size 0.34, 95% CI 0.02-0.66). Our results show that BDNF levels are associated with clinical changes in depression; supporting the notion that depression improvement is associated with neuroplastic changes.     

Repetitive Transcranial Magnetic Stimulation for Generalized Anxiety Disorder: A Systematic Literature Review and Meta-Analysis

BackgroundAnxiety disorders such as generalized anxiety disorder (GAD) impact 10% of the US population, and many patients do not completely respond to first-line treatments (e.g., selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and psychotherapy). Given the dearth of evidence for non-pharmacologic, non-psychotherapeutic interventions, we performed a systematic review and meta-analysis of repetitive transcranial magnetic stimulation (rTMS) in adults with GAD.MethodsA systematic literature review using the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was conducted. Pre- and post-treatment anxiety scores were extracted, and a random-effects meta-analysis was conducted to determine the magnitude of improvement (standardized mean difference). Standard assessments of heterogeneity (e.g., Q-statistic, I², and τ ²) and publication bias were performed.ResultsThe initial search resulted in 3194 citations, of which 6 studies were included in the meta-analysis. In total, 152 patients were studied, including 97 patients who received active treatment and 55 who received sham treatment, and heterogeneity was modest (I² 13.32, Q = 5.77). In patients with GAD, rTMS produced a standardized mean difference of −1.857 (confidence interval: −2.219 to −1.494; P < .001) with a prediction interval of −2.55 to −1.16.ConclusionsThe results suggest a robust effect of rTMS in GAD in the context of limited, heterogenous studies. Rigorously designed, randomized controlled trials of rTMS for GAD and related anxiety disorders are urgently needed. These studies will provide opportunities for biomarker development and integration of concurrent evidence-based psychotherapy to maximize results.     

综合疗法治疗高血压病伴焦虑及抑郁患者疗效的Meta分析

目的 了解应用综合疗法（降压药联合抗焦虑、抗抑郁心理治疗）治疗高血压病伴焦虑、抑郁患者的疗效. 方法 系统检索Pubmed,中文期刊全文数据库,万方数据库以及Internet公开发表的文献.检索词为高血压、焦虑、抑郁（主题题与自由词组合）.应用Meta分析文献中对于高血压病伴焦虑、抑郁患者,应用综合疗法的有效性进行同质性和异质性检验及合并效应量的估计. 结果 共收集到相关文献76篇,其中符合纳入标准的有20篇;14项研究总有效例数合并OR值为2.85[95% CI2.17～3.73],11项研究的收缩压合并标准化均数差值（SMD）为-1.13[95%CI-1.67～-0.58],舒张压合并SMD为-1.17[95%CI-1.87～-0.46]. 结论 应用综合疗法治疗高血压病伴焦虑、抑郁患者的疗效总体上明显高于单纯降压治疗组.     

Efficacy of statins in combination with interferon therapy in multiple sclerosis: A meta-analysis

Purpose The efficacy of statins in combination with interferon therapy in patients with multiple sclerosis (MS) is reviewed. Methods A systematic literature search was conducted through September 2011 to identify randomized controlled trials that evaluated the effect of combination statin-interferon therapy compared with interferon therapy alone in patients with MS. Trials had to report at least one of the following outcomes of interest: clinical relapse rate, disease progression, or Expanded Disability Status Scale (EDSS) score. A random-effects model was used to pool data. Trial quality was assessed using the Jadad score. Results Four unique trials were included in the analysis (n = 463 subjects; range of follow-up, 9-24 months), all with a Jadad score of ≥3. All trials evaluated patients with relapsing-remitting MS (RRMS). Most trials enrolled patients taking interferon beta therapy either twice or three times weekly. The mean baseline EDSS scores ranged from 1.2 to 3.4. Evaluated statins included simvastatin and atorvastatin. No significant difference was found between the statin and control groups in the incident rate ratio for clinical relapse (0.72; 95% confidence interval [CI], 0.17 to 3.11), risk of relapse (relative risk [RR], 0.99; 95% CI, 0.53 to 1.85], disease progression (RR, 1.31; 95% CI, 0.73 to 2.36), or difference in the change in the EDSS score from baseline (weighted mean difference, -0.06; 95% CI, -0.30 to 0.19). Conclusion A meta-analysis revealed that the addition of statins to interferon therapy did not significantly influence the relapse risk, disease progression, or EDSS scores in patients with RRMS.     

Repetitive transcranial magnetic stimulation : does it have potential in the treatment of depression?

Transcranial magnetic stimulation (TMS) has become a major research tool in experimental clinical neurophysiology as a result of its potential to noninvasively and focally stimulate cortical brain regions. Currently, studies are being conducted to investigate whether repetitive TMS (rTMS)-mediated modulation of cortical function may also provide a therapeutic approach in neurological and psychiatric disorders. Preclinical findings have shown that prefrontal rTMS can modulate the function of fronto-limbic circuits, which is reversibly altered in major depression. rTMS has also been found to exert effects on neurotransmitter systems involved in the pathophysiology of major depression (e.g. stimulates subcortical dopamine release and acts on the hypothalamic pituitary adrenal axis, which is dysregulated in depression). To date, numerous open and controlled clinical trials with widely differing stimulation parameters have explored the antidepressant potential of rTMS. Though conducted with small sample sizes, the majority of the controlled trials demonstrated significant antidepressant effects of active rTMS compared with a sham condition. Effect sizes, however, varied from modest to substantial, and the patient selection focused on therapy-resistant cases. Moreover, the average treatment duration was approximately 2 weeks, which is short compared with other antidepressant interventions. Larger multicentre trials, which would be mandatory to demonstrate the antidepressant effectiveness of rTMS, have not been conducted to date.A putative future application of rTMS may be the treatment of patients who did not tolerate or did not respond to antidepressant pharmacotherapy before trying more invasive strategies such as electroconvulsive therapy and vagus nerve stimulation. Theoretically, rTMS may be also applied early in the course of disease in order to speed up and increase the effects of antidepressant pharmacotherapy. However, this application has not been a focus of clinical trials to date. Research efforts should be intensified to further investigate the effectiveness of rTMS as an antidepressant intervention and to test specific applications of the technique in the treatment of depressive episodes.     

Meta-analysis of the association between ecstasy use and risky sexual behavior

A random-effects meta-analysis was conducted to examine the association between ecstasy use and risky sexual behavior. Analysis of 17 studies revealed a small to moderate sized effect (mean weighted r=0.211, 95% CI: 0.085-0.336). Random-effects homogeneity testing was non-significant, thus formal moderator analyses were not performed. Moreover, numerical and visual diagnostics suggested that publication bias was not a concern. It is hoped that the present meta-analytic findings and recommendations will encourage investigators to broaden their research methodologies and will stimulate new insights into the association between ecstasy use and risky sexual behavior.     

Modulation of risk-taking in marijuana users by transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC)

Cognitive deficits that are reported in heavy marijuana users (attention, memory, affect perception, decision-making) appear to be completely reversible after a prolonged abstinence period of about 28 days. However, it remains unclear whether the reversibility of these cognitive deficits indicates that (1) chronic marijuana use is not associated with long-lasting changes in cortical networks or (2) that such changes occur but the brain adapts to and compensates for the drug-induced changes. Therefore, we examined whether chronic marijuana smokers would demonstrate a differential pattern of response in comparison to healthy volunteers on a decision-making paradigm (Risk Task) while undergoing sham or active transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). Twenty-five chronic marijuana users who were abstinent for at least 24 h were randomly assigned to receive left anodal/right cathodal tDCS of DLPFC (n = 8), right anodal/left cathodal tDCS of DLPFC (n = 9), or sham stimulation (n = 8); results on Risk Task during sham/active tDCS were compared to healthy volunteers from a previously published dataset. Chronic marijuana users demonstrated more conservative (i.e. less risky) decision-making during sham stimulation. While right anodal stimulation of the DLPFC enhanced conservative decision-making in healthy volunteers, both right anodal and left anodal DLPFC stimulation increased the propensity for risk-taking in marijuana users. These findings reveal alterations in the decision-making neural networks among chronic marijuana users. Finally, we also assessed the effects of tDCS on marijuana craving and observed that right anodal/left cathodal tDCS of DLPFC is significantly associated with a diminished craving for marijuana.