Project description:Research into therapeutic transcranial magnetic stimulation (TMS) for major depression has dramatically increased in the last decade. Understanding the mechanism of action of TMS is crucial to improve efficacy and develop the next generation of therapeutic stimulation. Early imaging research provided initial data supportive of widely held assumptions about hypothesized inhibitory or excitatory consequences of stimulation. Early work also indicated that while TMS modulated brain activity under the stimulation site, effects at deeper regions, in particular, the subgenual anterior cingulate cortex, were associated with clinical improvement. Concordant with earlier findings, functional connectivity studies also demonstrated that clinical improvements were related to changes distal, rather than proximal, to the site of stimulation. Moreover, recent work suggests that TMS modulates and potentially normalizes functional relationships between neural networks. An important observation that emerged from this review is that similar patterns of connectivity changes are observed across studies regardless of TMS parameters. Though promising, we stress that these imaging findings must be evaluated cautiously given the widespread reliance on modest sample sizes and little implementation of statistical validation. Additional limitations included use of imaging before and after a course of TMS, which provided little insight into changes that might occur during the weeks of stimulation. Furthermore, as studies to date have focused on depression, it is unclear whether our observations were related to mechanisms of action of TMS for depression or represented broader patterns of functional brain changes associated with clinical improvement.
Project description:ObjectivesIt is estimated that 30-40% of adolescents with major depressive disorder (MDD) do not receive full benefit from current antidepressant therapies. Repetitive transcranial magnetic stimulation (rTMS) is a novel therapy approved by the US Food and Drug Administration to treat adults with MDD. Research suggests rTMS is not associated with adverse neurocognitive effects in adult populations; however, there is no documentation of its neurocognitive effects in adolescents. This is a secondary post hoc analysis of neurocognitive outcome in adolescents who were treated with open-label rTMS in two separate studies.MethodsEighteen patients (mean age, 16.2 ± 1.1 years; 11 females, 7 males) with MDD who failed to adequately respond to at least one antidepressant agent were enrolled in the study. Fourteen patients completed all 30 rTMS treatments (5 days/week, 120% of motor threshold, 10 Hz, 3,000 stimulations per session) applied to the left dorsolateral prefrontal cortex. Depression was rated using the Children's Depression Rating Scale-Revised. Neurocognitive evaluation was performed at baseline and after completion of 30 rTMS treatments with the Children's Auditory Verbal Learning Test (CAVLT) and Delis-Kaplan Executive Function System Trail Making Test.ResultsOver the course of 30 rTMS treatments, adolescents showed a substantial decrease in depression severity. Commensurate with improvement in depressive symptoms was a statistically significant improvement in memory and delayed verbal recall. Other learning and memory indices and executive function remained intact. Neither participants nor their family members reported clinically meaningful changes in neurocognitive function.ConclusionThese preliminary findings suggest rTMS does not adversely impact neurocognitive functioning in adolescents and may provide subtle enhancement of verbal memory as measured by the CAVLT. Further controlled investigations with larger sample sizes and rigorous trial designs are warranted to confirm and extend these findings.
Project description:BackgroundThe goal of this study was to examine baseline transcranial magnetic stimulation measures of cortical inhibition and excitability in depressed patients and characterize their longitudinal posttreatment changes.MethodsFifteen adolescents (age 13-17 years) with moderate to severe major depressive disorder and 22 healthy controls (age 9-17) underwent single- and paired-pulse transcranial magnetic stimulation and clinical assessments. Transcranial magnetic stimulation measures included short-interval intracortical inhibition (2 and 4 milliseconds), long-interval intracortical inhibition (100, 150, and 200 milliseconds), cortical silent period, and intracortical facilitation (10, 15, and 20 milliseconds). Ten participants with major depressive disorder initiated antidepressant treatment or had dose adjustments. These participants were reassessed after treatment. Depression symptom severity was measured with the Children's Depression Rating Scale, Revised. Robust regression modeling compared healthy and depressed adolescents at baseline. Relationships between changes in cortical inhibition and changes in depressive symptom severity were assessed in the depressed adolescents receiving antidepressant treatment.ResultsOur results revealed that at baseline, short-interval intracortical inhibition-2 was significantly reduced (Padj = .01) in depressed participants, suggesting impaired cortical inhibition compared with healthy controls. At follow-up, improvement in Children's Depression Rating Scale, Revised scores correlated with improvement in short-interval intracortical inhibition-4 amplitude (greater inhibition) after antidepressant treatment (R2 = 0.63; P = .01).ConclusionsThese results suggest that cortical inhibition measures may have promise as biomarkers in adolescents treated for depression.
Project description:BACKGROUND:Major depressive disorder (MDD) affects 10% of pregnancies. Because transcranial magnetic stimulation (TMS) is a nonmedication option, psychiatric patients who do not tolerate or prefer to avoid antidepressants are good candidates for TMS. METHOD:In a randomized controlled trial of twenty-two women with MDD in the second or third trimester of pregnancy, subjects were randomized to active TMS (n=11) or sham TMS (n=11). This study took place at a single academic center. Subjects received 20 sessions of TMS to the right dorsolateral prefrontal cortex at 1 Hz as a single train of 900 pulses per session at 100% motor threshold. Estradiol and progesterone and were measured before session 1 and after session 20. RESULTS:Results demonstrated significantly decreased Hamilton Depression Rating Scale (HDRS-17) scores for the active compared to the sham group (p=0.003). Response rates were 81.82% for the active and 45.45% for the sham coil (p=0.088). Remission rates were 27.27% for the active 18.18% for the sham coil (p=0.613). Late preterm birth (PTB) occurred in three women receiving active TMS. All other maternal and delivery outcomes were normal. CONCLUSIONS:Right-sided, low frequency TMS was effective in reducing depressive symptoms in this sample of pregnant women. There may be a possibility that TMS is associated with late PTB although a larger sample size would be needed for adequate power to detect a true difference between groups. This study demonstrated that TMS is low risk during pregnancy although larger trials would provide more information about the efficacy and safety of TMS in this population. This trial shows that an RCT of a biologic intervention in pregnant women with psychiatric illness can be conducted.
Project description:BackgroundStandard clinical protocols for repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder (MDD) apply 10 Hz pulses over left prefrontal cortex, yet little is known about the effects of rTMS in more diagnostically complex depressed patients.Objective/hypothesisPosttraumatic stress disorder (PTSD) is commonly comorbid with MDD, and while rTMS has been shown to alleviate PTSD symptoms in preliminary studies, ideal parameters remain unclear. We conducted a prospective, open-label study of 5 Hz rTMS for patients with comorbid PTSD + MDD and hypothesized stimulation would reduce symptoms of both disorders.MethodsOutpatients (N = 40) with PTSD + MDD and at least moderate global severity were enrolled. 5 Hz rTMS included up to 40 daily sessions followed by a 5-session taper. Symptoms were measured using the PTSD Checklist (PCL-5) and Inventory of Depressive Symptomatology, Self-Report (IDS-SR). Baseline-to-endpoint changes were analyzed.ResultsThe intent-to-treat population included 35 participants. Stimulation significantly reduced PTSD symptoms (PCL-5 baseline mean ± SD score 52.2 ± 13.1 versus endpoint 34.0 ± 21.6; p < .001); 23 patients (48.6%) met a pre-defined categorical PTSD response criteria. MDD symptoms also improved significantly (IDS-SR, baseline 47.8 ± 11.9 to endpoint 30.9 ± 18.9; p < .001); 15 patients (42.9%) demonstrated categorical response and 12 (34.3%) remitted. PTSD and MDD symptom change was highly correlated (r = 0.91, p < .001).LimitationsUnblinded single-arm study, with modest sample size.ConclusionSignificant and clinically meaningful reductions in both MDD and PTSD symptoms were observed following stimulation. The preliminary efficacy of 5 Hz rTMS for both symptom domains in patients with comorbid disorders supports future controlled studies.
Project description:ObjectivePreliminary studies suggest that repetitive transcranial magnetic stimulation (rTMS) may be an effective and tolerable intervention for adolescents with treatment-resistant depression. There is limited rationale to inform coil placement for rTMS dosing in this population. We sought to examine and compare three localization techniques for coil placement in the context of an open-label trial of high-frequency rTMS for adolescents with treatment-resistant depression.MethodsTen adolescents with treatment-resistant depression were enrolled in an open-label trial of high-frequency rTMS. Participants were offered 30 rTMS sessions (10 Hz, 120% motor threshold, left 3000 pulses applied to the dorsolateral prefrontal cortex) over 6-8 weeks. Coil placement for treatment was MRI guided. The scalp location for treatment was compared with the locations identified with standard 5 cm rule and Beam F3 methods.ResultsSeven adolescents completed 30 rTMS sessions. No safety or tolerability concerns were identified. Depression severity as assessed with the Children's Depression Rating Scale Revised improved from baseline to treatment 10, treatment 20, and treatment 30. Gains in depressive symptom improvement were maintained at 6 month follow-up visits. An MRI-guided approach for coil localization was feasible and efficient. Our results suggest that the 5 cm rule, Beam F3, and the MRI-guided localization approaches provided variable scalp targets for rTMS treatment.ConclusionsOpen-label, high-frequency rTMS was feasible, tolerable, and effective for adolescents with treatment-resistant depression. Larger, blinded, sham-controlled trials are needed for definitive safety and efficacy data. Further efforts to understand optimal delivery, dosing, and biomarker development for rTMS treatments of adolescent depression are warranted.
Project description:PurposeRepetitive Transcranial Magnetic Stimulation (rTMS) has been demonstrated to be effective in body weight control in individuals with obesity. Most clinical trials on rTMS provided a reassuring safety profile. In the present work, we present an extensive analysis on both severe and mild Adverse Events (AEs) in obese individuals treated with rTMS.MethodsWe examined the intensity, duration, correlation with the treatment, up to 1 year after the end of rTMS treatment.ResultsDescriptive analysis included a total of 63 subjects undergoing a 5-week deep rTMS experimental treatment for obesity (age 48.3 ± 10.4 years; BMI 36.3 ± 4.4 kg/m2): 31 patients were treated with high-frequency rTMS (HF), 13 with low-frequency rTMS (LF), and 19 were sham treated (Sham). Thirty-two subjects (50.8%) reported a total of 52 AEs, including mainly moderate (51.9%) events. The most frequently reported side effects were headaches of moderate intensity (40.4%) and local pain/discomfort (19.2%) and resulted significantly more frequent in HF group compared to other groups (p < 0.05). No significant differences among groups were found for the other reported AEs: drowsiness, insomnia, paresthesia, vasovagal reactions, hypertensive crisis. No AEs potentially related to the rTMS arised up to 1 year from the end of the treatment.ConclusionsThis is the first comprehensive safety analysis in obese patients treated with rTMS. The analysis did not reveal any unexpected safety concerns. Only headaches and local pain/discomfort have been significantly more frequent in the HF group, confirming the good tolerability of rTMS even in the obese population potentially more susceptible to side effects of brain stimulation.
Project description:Suicidal ideation increases precipitously in patients with depression, contributing to the risk of suicidal attempts. Despite the recent advancement in transcranial magnetic stimulation, its effectiveness in depression disorder and its wide acceptance, the network mechanisms of the clinical response to suicidal ideation in major depressive disorder remain unclear. Independent component analysis for neuroimaging data allows the identification of functional network connectivity which may help to explore the neural basis of suicidal ideation in major depressive disorder. Resting-state functional magnetic resonance imaging data and clinical scales were collected from 30 participants (15 major depressive patients with suicidal ideation and 15 healthy subjects). Individual target-transcranial magnetic stimulation (IT-TMS) was then used to decrease the subgenual anterior cingulate cortex activity through the left dorsolateral prefrontal cortex. Thirty days post IT-TMS therapy, seven of 15 patients (46.67%) met suicidal remission criteria, and 12 patients (80.00%) met depression remission criteria. We found that IT-TMS could restore the abnormal functional network connectivity between default mode network and precuneus network, left executive control network and sensory-motor network. Furthermore, the changes in functional network connectivity between the default mode network and precuneus network were associated with suicidal ideation, and depressive symptoms were related to connectivity between left executive control network and sensory-motor network. These findings illustrate that IT-TMS is an effective protocol for the accurate restoration of impaired brain networks, which is consistent with clinical symptoms.
Project description:Objective This meta-analysis of randomized clinical trials (RCTs) was conducted to explore the therapeutic effects, tolerability and safety of repetitive transcranial magnetic stimulation (rTMS) as an adjunct treatment in adolescents with first-episode major depressive disorder (FE-MDD). Methods RCTs examining the efficacy, tolerability and safety of adjunctive rTMS for adolescents with FE-MDD were included. Data were extracted by three independent authors and synthesized using RevMan 5.3 software with a random effects model. Results A total of six RCTs involving 562 adolescents with FE-MDD were included. Adjunctive rTMS was superior in improving depressive symptoms over the control group [standardized mean difference (SMD) = −1.50, 95% confidence interval (CI): −2.16, −0.84; I2 = 89%, p < 0.00001] in adolescents with FE-MDD. A sensitivity analysis and two subgroup analyses also confirmed the significant findings. Adolescents with FE-MDD treated with rTMS had significantly greater response [risk ratio (RR) = 1.35, 95% CI: 1.04, 1.76; I2 = 56%, p = 0.03] and remission (RR = 1.35, 95% CI: 1.03, 1.77; I2 = 0%, p = 0.03) over the control group. All-cause discontinuations were similar between the two groups (RR = 0.79, 95% CI: 0.32, 1.93; I2 = 0%, p = 0.60). No significant differences were found regarding adverse events, including headache, loss of appetite, dizziness and nausea (p = 0.14–0.82). Four out of six RCTs (66.7%), showed that adjunctive rTMS was more efficacious over the control group in improving neurocognitive function (all p < 0.05). Conclusion Adjunctive rTMS appears to be a beneficial strategy in improving depressive symptoms and neurocognitive function in adolescents with FE-MDD. Higher quality RCTs with larger sample sizes and longer follow-up periods are warranted in the future.
Project description:Major depressive disorder (MDD) is a mental illness with high socio-economic burden, but its pathophysiology has not been fully elucidated. Recently, the cortical excitatory and inhibitory imbalance hypothesis and neuroplasticity hypothesis have been proposed for MDD. Although several studies have examined the neurophysiological profiles in MDD using transcranial magnetic stimulation (TMS), a meta-analysis of TMS neurophysiology has not been performed. The objective of this study was to compare TMS-electromyogram (TMS-EMG) findings between patients with MDD and healthy controls (HCs). To this end, we examined whether patients with MDD have lower short-interval cortical inhibition (SICI) which reflects gamma-aminobutyric acid (GABA)A receptor-mediated activity, lower cortical silent period (CSP) which represents GABAB receptor-mediated activity, higher intracortical facilitation (ICF) which reflects glutamate N-methyl-D-aspartate receptor-mediated activity, and the lower result of paired associative stimulation (PAS) paradigm which shows the level of neuroplasticity in comparison with HC. Further, we explored the effect of clinical and demographic factors that may influence TMS neurophysiological indices. We first searched and identified research articles that conducted single- or paired-pulse TMS-EMG on patients with MDD and HC. Subsequently, we extracted the data from the included studies and meta-analyzed the data with the comprehensive meta-analysis software. Patients with MDD were associated with lower SICI, lower CSP, potentially higher ICF, and lower PAS compared with HC. Our results confirmed the proposed hypotheses, suggesting the usefulness of TMS neurophysiology as potential diagnostic markers of MDD.