Depressive Disorders

Experimental neurology, 2009

Brain Stimulation, 2015

Journal of psychiatry & neuroscience : JPN, 2003

Background: Studies suggest that the dorsolateral prefrontal cortex (DLPFC) participates in neural circuitry that is dysregulated in Panic Disorder (PD) and Major Depressive Disorder (MDD). We tested whether low-frequency repetitive Transcranial Magnetic Stimulation (rTMS) could normalize the overactivity of right frontal regions and thereby improve symptoms. Methods: Six patients with PD and comorbid MDD were treated with daily active 1-Hz rTMS to the right DLPFC for 2 weeks in this open-label trial. Results: Clinical improvements were apparent as early as the first week of treatment. After the second week, 5/6 of patients showed improvements in panic and anxiety, and 4/6 showed a decrease in depression, with sustained improvement at 6 months of followup. Right hemisphere resting motor threshold increased significantly after rTMS. Limitations: Limitations of this study are the open design and the small sample size. Conclusions: Slow rTMS to the right DLPFC resulted in significant clinical improvement and reduction of ipsilateral motor cortex excitability. Replications in larger sample will help to clarify the relevance of this preliminary data and to define the potential role of right DLPFC rTMS in panic with major depression.

Indian Journal of Psychological Medicine, 2011

Transcranial magnetic stimulation (TMS) is a noninvasive application of pulsed magnetic field near an area of scalp, which causes depolarization of neurons in underlying part of cerebral cortex. At cellular level, mechanisms of electroconvulsive therapy (ECT) and TMS are the same. [1] In psychiatry, the application of rTMS was tested including major depressive disorder (MDD) [2,3] which was based on observation that a single pulse of magnetic stimulation elevated the mood for some period, though it was transient. Current challenges in the field include determining how to enhance the efficacy of rTMS in the psychiatric disorders and how to identify patients for whom rTMS can be a useful method of treatment. Depression is a common disorder with serious personal, interpersonal, and societal consequences, affecting about 15% of the general population and accounting for approximately 10% of consultations in primary care. [4] The World Health Organization has ranked MDD as the fourth most disabling disorder. [5] Despite New Horizon About 30 to 46% of patients with major depressive disorder (MDD) fail to fully respond to initial antidepressants. Treatmentresistant depression (TRD) is a severely disabling disorder with no proven treatment options; novel treatment methods like rTMS can be used as augmentation to ongoing pharmacotherapy or as a solitary method of treatment. To evaluate the utility of repetitive transcranial magnetic stimulation as an augmenting method in TRD. In an open-label study, 21 patients with DSM-IV MDD without psychotic features who had failed to respond to an adequate trial of at least 2 antidepressants were given rTMS therapy for 4 weeks, keeping the dose of pre-existing antidepressants unchanged. High-frequency (10 Hz) stimulations were delivered over left dorsolateral prefrontal cortex at intensity of 110% of patient's motor threshold. Treatment response was defined as a reduction in score on the Hamilton Rating Scale for Depression (HAM-D) from baseline to end of treatment. Secondary efficacy measures included scores on the Clinical Global Impressions-Change and-Severity scales. At the end of 4 weeks, 19 patients completed the 4-week study and were assessed. In ITT analysis, the mean HAM-D17 scores were reduced from 30.80±5.00 to 19.00±6.37 (t=8.27, P<0.001). Only four patients reported headache, but there was no discontinuation due to adverse effects. The study indicates the potential utility of rTMS as an augmenting agent in TRD. Adequately powered, randomized controlled trials are necessary to evaluate the role of rTMS in TRD.

Brain Stimulation, 2018

Background: Evidence suggests that transcranial Direct Current Stimulation (tDCS) has antidepressant effects in unipolar depression, but there is limited information for patients with bipolar depression. Additionally, prior research suggests that brain derived neurotrophic factor (BDNF) Val66Met genotype may moderate response to tDCS. Objective: To examine tDCS efficacy in unipolar and bipolar depression and assess if BDNF genotype is associated with antidepressant response to tDCS. Methods: 130 participants diagnosed with a major depressive episode were randomized to receive active (2.5 milliamps (mA), 30 min) or sham (0.034 mA and two 60-second current ramps up to 1 and 0.5 mA) tDCS to the left prefrontal cortex, administered in 20 sessions over 4 weeks, in a double-blinded, international multisite study. Mixed effects repeated measures analyses assessed change in mood and neuropsychological scores in participants with at least one post-baseline rating in the unipolar (N ¼ 84) and bipolar (N ¼ 36) samples. Results: Mood improved significantly over the 4-week treatment period in both unipolar (p ¼ 0.001) and bipolar groups (p < 0.001). Among participants with unipolar depression, there were more remitters in the sham treatment group (p ¼ 0.03). There was no difference between active and sham stimulation in the bipolar sample. BDNF genotype was unrelated to antidepressant outcome. Conclusions: Overall, this study found no antidepressant difference between active and sham stimulation for unipolar or bipolar depression. However, the possibility that the low current delivered in the sham tDCS condition was biologically active cannot be discounted. Moreover, BDNF genotype did not moderate antidepressant outcome. Clinical Trials Registration: www.clinicaltrials.gov, NCT01562184.

Journal of Affective Disorders, 2009

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that applies mild (typically 1-2 mA) direct currents via the scalp to enhance or diminish neuronal excitability. The technique has a dual function: on the one hand, it has been used to investigate the functions of various cortical regions; on the other, it has been used as an experimental treatment modality, most notably for Major Depressive Disorder (MDD). With the growing utility of tDCS in psychiatry, it is important from the vantage of safety and effectiveness to understand its underlying neurobiological mechanisms. In this respect, researchers have made significant progress in recent years, highlighting changes in resting membrane potential, spontaneous neuronal firing rates, synaptic strength, cerebral blood flow and metabolism subsequent to tDCS. We briefly review tDCS clinical trials for MDD, and then consider its mechanisms of action, identifying potential avenues for future research.

Journal of Affective Disorders, 2011

Biological Psychiatry, 2006

Rapid transcranial magnetic stimulation (rTMS) applied to the left dorsal lateral frontal cortex has been shown to produce antidepressant effects. Older depressed patients, however, in one study showed a lower response rate than younger patients. The current study examined treatment response in 20 depressed, treatment-refractory patients (mean age 60.7 * 9.8 years) given five sessions of rTh4S at 20 Hz for 2 seconds over 20 trains at 80% of motor threshold or identical placebo stimulation, after patients had been withdrawn from their antidepressants. There were no significant differences in Hamilton Depression Scale scores either before or after treatment at 7 days' follow-up. There were three responders to active treatment and three to sham treatment and responders had significantly greater frontal lobe volume than nonresponders (p = .03). These findings suggest that the stimulation parameters used in this study were probably insufficient to produce treatment response and that frontal atrophy may interfere with the effectiveness of rTMS. Transcranial magnetic stimulators capable of discharging repetitively in trains have provided a technology that allows modulating human cortical excitability noninvasively, safely, and practically painlessly (Pascual-Leone et al., 1996).

Australian and New Zealand Journal of Psychiatry, 2006

Objective: To review the accumulated literature on the efficacy, safety and predictors of response for repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression. Methods: A descriptive review of the more than 25 published sham-controlled rTMS studies in depression was undertaken, focusing on reported meta-analyses as well as individual trial reports. Potential determinants of efficacy were examined, including the form of shams employed, stimulation parameters and clinical features. Results: There is now clear evidence for the statistical superiority of left-prefrontal high frequency rTMS compared with sham therapy. However, the clinical benefits are marginal in the majority of reports. There is also still considerable uncertainty concerning the optimal stimulation parameters. Those clinical features which appear to be associated with greater response include younger age, lack of refractoriness to antidepressants and no psychotic features. Conclusions: Curren...

Journal of psychiatric …, 2007