Transcranial direct current stimulation for major depression: an updated systematic review and meta-analysis.

Transcranial direct cranial stimulation (tDCS) is a promising non-pharmacological intervention for treating major depressive disorder (MDD). However, results from randomized controlled trials (RCTs) and meta-analyses are mixed. Our aim was to assess the efficacy of tDCS as a treatment for MDD. We performed a systematic review in Medline and other databases from the first RCT available until January 2014. The main outcome was the Hedges' g for continuous scores; secondary outcomes were the odds ratio (ORs) to achieve response and remission. We used a random-effects model. Seven RCTs (n = 259) were included, most with small sample sizes that assessed tDCS as either a monotherapy or as an add-on therapy. Active vs. sham tDCS was significantly superior for all outcomes (g = 0.37; 95% CI 0.04-0.7; ORs for response and remission were, respectively, 1.63; 95% CI = 1.26-2.12 and 2.50; 95% CI = 1.26-2.49). Risk of publication bias was low. No predictors of response were identified, possibly owing to low statistical power. In summary, active tDCS was statistically superior to sham tDCS for the acute depression treatment, although its role as a clinical intervention is still unclear owing to the mixed findings and heterogeneity of the reviewed studies. Further RCTs with larger sample sizes and assessing tDCS efficacy beyond the acute depressive episode are warranted.

Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: A Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial.

(Appeared originally in American Journal of Psychiatry 2019; 176:931-938) Reprinted with permission from American Psychiatric Association Publishing.

Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines.

This article is based on a consensus conference, promoted and supported by the International Federation of Clinical Neurophysiology (IFCN), which took place in Siena (Italy) in October 2018. The meeting intended to update the ten-year-old safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings (Rossi et al., 2009). Therefore, only emerging and new issues are covered in detail, leaving still valid the 2009 recommendations regarding the description of conventional or patterned TMS protocols, the screening of subjects/patients, the need of neurophysiological monitoring for new protocols, the utilization of reference thresholds of stimulation, the managing of seizures and the list of minor side effects. New issues discussed in detail from the meeting up to April 2020 are safety issues of recently developed stimulation devices and pulse configurations; duties and responsibility of device makers; novel scenarios of TMS applications such as in the neuroimaging context or imaging-guided and robot-guided TMS; TMS interleaved with transcranial electrical stimulation; safety during paired associative stimulation interventions; and risks of using TMS to induce therapeutic seizures (magnetic seizure therapy). An update on the possible induction of seizures, theoretically the most serious risk of TMS, is provided. It has become apparent that such a risk is low, even in patients taking drugs acting on the central nervous system, at least with the use of traditional stimulation parameters and focal coils for which large data sets are available. Finally, new operational guidelines are provided for safety in planning future trials based on traditional and patterned TMS protocols, as well as a summary of the minimal training requirements for operators, and a note on ethics of neuroenhancement.

Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: A Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a chronic and disabling condition that often responds unsatisfactorily to pharmacological and psychological treatments. Converging evidence suggests a dysfunction of the cortical-striatal-thalamic-cortical circuit in OCD, and a previous feasibility study indicated beneficial effects of deep transcranial magnetic stimulation (dTMS) targeting the medial prefrontal cortex and the anterior cingulate cortex. The authors examined the therapeutic effect of dTMS in a multicenter double-blind sham-controlled study. METHODS: At 11 centers, 99 OCD patients were randomly allocated to treatment with either high-frequency (20 Hz) or sham dTMS and received daily treatments following individualized symptom provocation, for 6 weeks. Clinical response to treatment was determined using the Yale-Brown Obsessive Compulsive Scale (YBOCS), and the primary efficacy endpoint was the change in score from baseline to posttreatment assessment. Additional measures were response rates (defined as a reduction of ≥30% in YBOCS score) at the posttreatment assessment and after another month of follow-up. RESULTS: Eighty-nine percent of the active treatment group and 96% of the sham treatment group completed the study. The reduction in YBOCS score among patients who received active dTMS treatment was significantly greater than among patients who received sham treatment (reductions of 6.0 points and 3.3 points, respectively), with response rates of 38.1% and 11.1%, respectively. At the 1-month follow-up, the response rates were 45.2% in the active treatment group and 17.8% in the sham treatment group. Significant differences between the groups were maintained at follow-up. CONCLUSIONS: High-frequency dTMS over the medial prefrontal cortex and anterior cingulate cortex significantly improved OCD symptoms and may be considered as a potential intervention for patients who do not respond adequately to pharmacological and psychological interventions.

The treatment of recurring auditory hallucinations in schizophrenia with rTMS.

BACKGROUND: Auditory hallucinations are a common and disabling problem for many patients with schizophrenia and often fail to respond to optimal antipsychotic therapy. Repetitive transcranial magnetic stimulation (rTMS) has recently been trialled as an alternative treatment option for these patients. These studies have generally been positive, but treatment has only been provided for short periods of time and little is known about the longer-term impact of TMS on the course of hallucinations. METHOD: We describe two cases in which rTMS was provided to patients upon relapse of hallucinations following initial successful rTMS treatment in a clinical trial. RESULTS: A repeat course of rTMS resulted in a marked improvement in the symptoms experienced by these two patients. CONCLUSIONS: rTMS appears to have potential as a long-term treatment for patients with auditory hallucinations, but requires ongoing systematic investigation.

A study of the effects of lorazepam and dextromethorphan on the response to cortical 1 Hz repetitive transcranial magnetic stimulation.

We studied the effects of lorazepam and dextromethorphan on the responses to 1 Hz repetitive transcranial magnetic stimulation applied to the left human motor cortex. Lorazepam, dextromethorphan or placebo was administered to 45 normal controls in a double-blind fashion 2.5 h before the repetitive transcranial magnetic stimulation procedure. Motor cortical excitability was measured with single transcranial magnetic stimulation pulses before and after 15 min of 1 Hz repetitive transcranial magnetic stimulation applied at supra-threshold intensity. 1 Hz repetitive transcranial magnetic stimulation resulted in a decrease in motor cortical excitability in the placebo group but not in the groups taking lorazepam or dextromethorphan. These results suggest that cortical responses to 1 Hz repetitive transcranial magnetic stimulation are dependent on activity at both gamma-aminobutyric acid and N-methyl-D-asparate receptor systems.

A double-blind sham-controlled trial of repetitive transcranial magnetic stimulation in the treatment of refractory auditory hallucinations.

BACKGROUND: Previous research suggests that repetitive transcranial magnetic stimulation (rTMS) applied to the temporoparietal cortex may have therapeutic benefits for patients with schizophrenia and treatment-resistant auditory hallucinations. We aimed to test this hypothesis in a randomized double-blind trial. METHODS: Thirty-three patients with treatment-resistant auditory hallucinations entered a randomized sham-controlled, double-blind trial. rTMS was applied for 10 consecutive weekdays, for 15 minutes at 1 Hz and 90% of the resting motor threshold. We assessed clinical symptoms and cognitive function. RESULTS: rTMS was safe with no adverse effects on memory and cognitive parameters assessed. Active treatment did not result in a greater therapeutic effect than sham on any measure except for the loudness of hallucinations where there was a significant reduction in the active versus the sham group over time. CONCLUSIONS: The study does not support the effectiveness of rTMS using the stimulation parameters provided. However, it does suggest that rTMS methods may have a therapeutic role and indicates the need for further exploration of alternative and more effective stimulation methods.