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Interventional effects of low-frequency repetitive transcranial magnetic stimulation on patients with depression after traumatic brain injury

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Abstract

Aim: To study the therapeutic effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on patients with depression after traumatic brain injury (TBI), and explore its mechanism. Methods: Depressive patients after TBI were evaluated by using the Hamilton rating scale for depression (HAMD), and then the positive results were randomly divided into study group (n = 32) and control group (n = 32). All the patients received routine antidepression drug treatment, besides, patients in the study group were treated with rTMS, and they were stimulated with 60% of the maximum stimulus intensity at the bilateral frontal lobes, 30 times to each side with the frequency of 0.5 Hz, once a day. All the patients were evaluated with HAMD and mini-mental state examination (MMSE) and the concentrations of monoamine neurotransmitters in plasma were examined before and after treatment. Results: The scores of HAMD and MMSE after treatment in the study group were (6 ± 6) and (23 ± 5) points, and those in the control group were (12 ± 8) and (18 ± 5) points. The concentration of 5-hydroxytryptamine(5-HT) after treatment was (1.42 ± 0.37) μmol/L in the treatment group and (1.35 ± 0.36) μmol/L in the control group. The concentrations of noradrenaline (NA) in the study group and control group were (0.41 ± 0.04) μmol/L and (0.35 ± 0.05) μmol/L respectively, and there were significant differences between the two groups (t = 2.316, P = 0.034 8, t = 2.177 4, P = 0.035 6, t = 5.743 6, P = 0.008, t = 6.473 2, P = 0.009). The recent effective rate was 90%, while the long-term effective rate needed further observation. Conclusion: Low-frequency rTMS relieves the depressive symptoms and improves the quality of life in patients with depression after TBI.

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... There are limited published studies in the literature on the use of rTMS for treating TBI depression. Three studies have been identified: a case report by Fitzgerald et al. (25), a case report by Nielson et al. (26), and a randomized trial by He et al. (27) comparing rTMS and a tricyclic antidepressant with a tricyclic antidepressant alone. All three studies reported positive effects of rTMS on depressive symptoms. ...
Article
Objective: Major depression is the most common psychiatric sequela of traumatic brain injury (TBI), but effective treatment continues to be a challenge, with few studies providing guidance. Methods: In a pilot study, the authors evaluated the effect size of low-frequency right-sided (LFR) repetitive transcranial magnetic stimulation (rTMS), compared with sham treatment, over the right dorsolateral prefrontal cortex (DLPFC) in patients (N=30) with TBI depression and co-occurring neuropsychiatric symptoms, including suicidal thoughts, anxiety, posttraumatic stress disorder, sleep disturbance, behavioral problems, and cognitive dysfunction. Exploratory analyses of diffusion tensor imaging pre- and postintervention were performed to determine the effect size of LFR rTMS on white matter integrity. Results: Small (Hedge's g=0.19) and highly variable effects of LRF rTMS over right DLPFC in TBI depression were observed. Similarly, the effect of LFR rTMS for treatment of comorbid neuropsychiatric symptoms varied from small to moderate. Conclusions: These findings suggest that the observed effects of LFR rTMS over the right DLPFC in TBI depression and co-occurring neuropsychiatric symptoms are small, at best, and, preliminarily, that low-frequency right DLPFC stimulation has limited potential in this patient population. However, studies employing different rTMS parameters (e.g., type, location, frequency, duration) or other participant characteristics (e.g., TBI severity, chronicity, comorbidity, concurrent treatment) may potentially yield different responses.
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Background: Depression is an important morbidity associated with stroke that impacts on recovery yet often undetected or inadequately treated. This is an update and expansion of a Cochrane Review first published in 2004 and updated in 2008. Objectives: Primary objective • To determine whether pharmacological therapy, non-invasive brain stimulation, psychological therapy, or combinations of these interventions reduce the prevalence of diagnosable depression after stroke Secondary objectives • To determine whether pharmacological therapy, non-invasive brain stimulation, psychological therapy, or combinations of these interventions reduce levels of depressive symptoms, improve physical and neurological function and health-related quality of life, and reduce dependency after stroke • To assess the safety of and adherence to such treatments SEARCH METHODS: We searched the Specialised Registers of Cochrane Stroke and Cochrane Depression Anxiety and Neurosis (last searched August 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1), in the Cochrane Library, MEDLINE (1966 to August 2018), Embase (1980 to August 2018), the Cumulative Index to Nursing and Alllied Health Literature (CINAHL) (1982 to August 2018), PsycINFO (1967 to August 2018), and Web of Science (2002 to August 2018). We also searched reference lists, clinical trial registers (World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) to August 2018; ClinicalTrials.gov to August 2018), and conference proceedings, and we contacted study authors. Selection criteria: Randomised controlled trials comparing (1) pharmacological interventions with placebo; (2) one of various forms of non-invasive brain stimulation with sham stimulation or usual care; (3) one of various forms of psychological therapy with usual care and/or attention control; (4) pharmacological intervention and various forms of psychological therapy with pharmacological intervention and usual care and/or attention control; (5) non-invasive brain stimulation and pharmacological intervention with pharmacological intervention and sham stimulation or usual care; (6) pharmacological intervention and one of various forms of psychological therapy with placebo and psychological therapy; (7) pharmacological intervention and non-invasive brain stimulation with placebo plus non-invasive brain stimulation; (8) non-invasive brain stimulation and one of various forms of psychological therapy versus non-invasive brain stimulation plus usual care and/or attention control; and (9) non-invasive brain stimulation and one of various forms of psychological therapy versus sham brain stimulation or usual care plus psychological therapy, with the intention of treating depression after stroke. Data collection and analysis: Two review authors independently selected studies, assessed risk of bias, and extracted data from all included studies. We calculated mean difference (MD) or standardised mean difference (SMD) for continuous data, and risk ratio (RR) for dichotomous data, with 95% confidence intervals (CIs). We assessed heterogeneity using the I² statistic and certainty of the evidence according to GRADE. Main results: We included 49 trials (56 comparisons) with 3342 participants. Data were available for: (1) pharmacological interventions with placebo (with 20 pharmacological comparisons); (2) one of various forms of non-invasive brain stimulation with sham stimulation or usual care (with eight non-invasive brain stimulation comparisons); (3) one of various forms of psychological therapy with usual care and/or attention control (with 16 psychological therapy comparisons); (4) pharmacological intervention and various forms of psychological therapy with pharmacological intervention and usual care and/or attention control (with two comparisons); and (5) non-invasive brain stimulation and pharmacological intervention with pharmacological intervention and sham stimulation or usual care (with 10 comparisons). We found no trials for the following comparisons: (6) pharmacological intervention and various forms of psychological therapy interventions versus placebo and psychological therapy; (7) pharmacological intervention and non-invasive brain stimulation versus placebo plus non-invasive brain stimulation; (8) non-invasive brain stimulation and one of various forms of psychological therapy versus non-invasive brain stimulation plus usual care and/or attention control; and (9) non-invasive brain stimulation and one of various forms of psychological therapy versus sham brain stimulation or usual care plus psychological therapy. Treatment effects observed: very low-certainty evidence from eight trials suggests that pharmacological interventions decreased the number of people meeting study criteria for depression (RR 0.70, 95% CI 0.55 to 0.88; 1025 participants) at end of treatment, and very low-certainty evidence from six trials suggests that pharmacological interventions decreased the number of people with less than 50% reduction in depression scale scores at end of treatment (RR 0.47, 95% CI 0.32 to 0.69; 511 participants) compared to placebo. No trials of non-invasive brain stimulation reported on meeting study criteria for depression at end of treatment. Only one trial of non-invasive brain stimulation reported on the outcome <50% reduction in depression scale scores; thus, we were unable to perform a meta-analysis for this outcome. Very low-certainty evidence from six trials suggests that psychological therapy decreased the number of people meeting the study criteria for depression at end of treatment (RR 0.77, 95% CI 0.62 to 0.95; 521 participants) compared to usual care/attention control. No trials of combination therapies reported on the number of people meeting the study criteria for depression at end of treatment. Only one trial of combination (non-invasive brain stimulation and pharmacological intervention) therapy reported <50% reduction in depression scale scores at end of treatment. Thus, we were unable to perform a meta-analysis for this outcome. Five trials reported adverse events related to the central nervous system (CNS) and noted significant harm in the pharmacological interventions group (RR 1.55, 95% CI 1.12 to 2.15; 488 participants; very low-certainty evidence). Four trials found significant gastrointestinal adverse events in the pharmacological interventions group (RR 1.62, 95% CI 1.19 to 2.19; 473 participants; very low-certainty evidence) compared to the placebo group. No significant deaths or adverse events were found in the psychological therapy group compared to the usual care/attention control group. Non-invasive brain stimulation interventions and combination therapies resulted in no deaths. Authors' conclusions: Very low-certainty evidence suggests that pharmacological or psychological therapies can reduce the prevalence of depression. This very low-certainty evidence suggests that pharmacological therapy, psychological therapy, non-invasive brain stimulation, and combined interventions can reduce depressive symptoms. Pharmacological intervention was associated with adverse events related to the CNS and the gastrointestinal tract. More research is required before recommendations can be made about the routine use of such treatments.
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Concussion and Traumatic Encephalopathy - edited by Jeff Victoroff February 2019
Article
OBJECTIVE: To evaluate the effects of transcranial magnetic stimulation (TMS) on post-stroke dysfunction. DATA SOURCES: A computer-based online search of the VIP and PubMed databases was performed to identify TMS studies published between January 1989 and December 2010 using the key words "transcranial magnetic stimulation, stroke" in Chinese and English. A total of 61 articles were collected. STUDY SELECTION: Repetitive articles were excluded. Articles published recently in the authoritative journals of the same domain were selected. The full-text of selected articles was searched. A total of seven articles were randomized controlled experiments regarding the application of TMS in the treatment of post-stroke dysfunction. The methodology quality of included articles was evaluated according to standards of Cochrane Reviewer's Handbook system and analyzed using RevMand4.2 software. MAIN OUTCOME MEASURES: Therapeutic effects and difference evaluation indices were represented by odds ratios, weighted mean difference (WMD) and 95% confidence interval (CI). Potential publication bias was described using a funnel plot. RESULTS: A total of seven randomized, controlled studies were included involving 281 patients. Following TMS treatment, meta-analysis results revealed that scores in the Mini-Mental State Examination were higher in the TMS group compared with the control group [WMD = 3.96, 95% CI (2.44, 5.49), P = 0.08]; scores in the Hamilton Rating Scale for Depression were significantly lower in the TMS group compared with the control group [WMD = -6.21, 95% CI (-7.55, -4.87), P = 0.92]; scores in National Institutes of Health Stroke Scale were lower following TMS treatment compared with the control group [WMD = -0.89, 95% CI (-1.98, 0.19), P = 0.04]. Performance of patients undergoing TMS treatment was better than the controls in the line bisection test [WMD = -0.78, 95% CI (-1.43, -0.12), P = 0.005] and line cancellation test [WMD = -0.47, 95% CI (-0.78, -0.15), P < 0.000 01]. Sensitivity analysis produced identical results after eliminating articles with unknown diagnostic standards or statistical methods. CONCLUSION: TMS effectively improved post-stroke dysfunction, manifested by improved cognitive function and memory performance compared with controls.
Article
Background: Following traumatic brain injury (TBI) there is an increased prevalence of depression compared to the general population. It is unknown whether non-pharmacological interventions for depression are effective for people with TBI. Objectives: To investigate the effectiveness of non-pharmacological interventions for depression in adults and children with TBI at reducing the diagnosis and severity of symptoms of depression. Search methods: We ran the most recent search on 11 February 2015. We searched the Cochrane Injuries Group Specialised Register, The Cochrane Library, MEDLINE (OvidSP), Embase (OvidSP), three other databases and clinical trials registers. Relevant conference proceedings and journals were handsearched, as were the reference lists of identified studies. Selection criteria: Randomised controlled trials (RCTs) of non-pharmacological interventions for depression in adults and children who had a TBI. Data collection and analysis: Two authors independently selected trials from the search results, then assessed risk of bias and extracted data from the included trials. The authors contacted trial investigators to obtain missing information. We rated the overall quality of the evidence of the primary outcomes using the GRADE approach. Main results: Six studies met the inclusion criteria, with a total of 334 adult participants. We identified no studies that included children as participants. All studies were affected by high risk of bias due to a lack of blinding of participants and personnel; five studies were affected by high risk of bias for lack of blinding of outcome assessors. There was high or unclear risk of biases affecting some studies across all the Cochrane risk of bias measures.Three studies compared a psychological intervention (either cognitive behaviour therapy or mindfulness-based cognitive therapy) with a control intervention. Data regarding depression symptom outcome measures were combined in a meta-analysis, but did not find an effect in favour of treatment (SMD -0.14; 95% CI -0.47 to 0.19; Z = 0.83; P = 0.41). The other comparisons comprised of single studies of depression symptoms and compared; cognitive behaviour therapy versus supportive psychotherapy (SMD -0.09; 95% CI -0.65 to 0.48; Z = 0.30; P = 0.77); repetitive transcranial magnetic stimulation plus tricyclic antidepressant (rTMS + TCA) versus tricyclic antidepressant alone (SMD -0.84; 95% CI -1.36 to -0.32; Z = 3;19, P = 0.001); and a supervised exercise program versus exercise as usual (SMD -0.43; 95% CI -0.88 to 0.03; Z = 1.84; P = 0.07). There was very-low quality evidence, small effect sizes and wide variability of results, suggesting that no comparisons showed a reliable effect for any intervention.Only one study mentioned minor, transient adverse events from repetitive transcranial magnetic stimulation. Authors' conclusions: The review did not find compelling evidence in favour of any intervention. Future studies should focus on participants with a diagnosed TBI and include only participants who have a diagnosis of depression, or who record scores above a clinical cutoff on a depression measure. There is a need for additional RCTs that include a comparison between an intervention and a control that replicates the effect of the attention given to participants during an active treatment.
Article
Aim: To study the effects of hypericin on the behavior and expressions of 5-hydroxytryptamine(5-HT), noradrenaline(NA) in the brain of rats with depression. Methods: Totally 72 male Wistar rats were selected in this experiment to establish models of chronic stress-induced depression. Open-field test, step-down avoidance test and immunohistochemistry staining were employed to study the effects of the extract of the fruit of Hypericum perforatum (EFHP) on praxiology and cerebral pathology in the rat models. Results: In open-field test, the number of crossing and rearing was significantly lower in chronic stress-induced depression rats than the control rats (P < 0.01). At the doses of 150.0 and 75.0 mg/kg, EFHP increased the number of crossing and rearing (P < 0.05 and P < 0.01, respectively) in comparison with the model group; at the dose of 37.5 mg/kg, EFHP increased the number of crossings to 27 ± 4, significantly higher than that in the model group (18 ± 5) (P < 0.05). At the doses of 150 and 75 mg/kg, EFHP significantly decreased the staying time of erroneous reaction in step-down avoidance test to 18 ± 30 and 23 ± 43 respectively as compared with the model group (116 ± 129) (P < 0.05); EFHP also increased the expression of 5-HT, NA in rat brain in comparison with the model group (P < 0.01). Conclusion: Hypericin improves depression in rats through increasing the expressions of NA and 5-HT.
Article
This study tries to evaluate the hypothesis of an association between severity of post-stroke depression and reduced cerebral blood flow (SPECT Xenon-133). 37 patients in the fourth week of post-stroke evolution with RDS criteria of major depression (N = 20) and non-depressed patients (N = 17) were compared in regard to following parameters: values of cerebral blood flow (SPECT Xenon-133), localization of brain lesion (CT Scanner) and quantitative measurement of mood (HDRS, MARDS, BDI), functional ability (Barthel, Karnofsky), cognitive function (MMSE, WPT) and neurological function (Orgogozo's Scale). Post-stroke major depression is more frequent (NS) in left and anterior lesions. We also demonstrated a significant association between total brain hypoperfusion and 1) severity of post-stroke depression, 2) severity of neurologic and functional impairments. these results suggest a relationship between mood and cerebral perfusion following stroke.
Article
Recent research indicates that post-stroke depression results from neurobiological changes associated with focal cerebral injury. Family or medical personnel may identify potential depression. An accurate assessment process will determine the extent of depression and indicate treatment options. Treatment approaches using both medication and cognitive therapy can help the individual replace negative thinking patterns with positive patterns. Depression has been accepted as a normal accompaniment of stroke. The area of injury may correlate with the degree of mood disorder. Interventions to reverse depression will serve to improve rehabilitation potential and increase chances of recovering pre-stroke capabilities.
Article
Studies in humans show antidepressant potential for transcranial magnetic stimulation (TMS). We therefore studied TMS in animal models of depression and compared its effects with those of ECS. ECS in rats has several robust behavioral effects, including enhancement of apomorphine-induced stereotypy, reduction of immobility time in the Porsolt swim test, and increases in seizure threshold for subsequent stimulation. Seven or 10 days of daily TMS consistently enhanced apomorphine-induced stereotypy, whereas a single session of TMS did not. Two TMS treatments markedly reduced immobility in the Porsolt swim test, as does ECS. A single TMS treatment markedly reduces the percentage of rats seizing in response to a ECS-like electrical stimulus to the brain 10 s later, as does an ECS treatment itself but not a sub-convulsive electrical stimulus to the brain. Long-term administration of ECS as well as other antidepressant treatments downregulates beta-adrenergic receptors. We found that TMS significantly reduced the density of [3H]CGP-12177 (a radioligand with beta-adrenergic affinity) binding sites in cortical (p < 0.05) but not hippocampal membranes. The role of monoamines in the mechanism of action of antidepressant treatments was investigated in numerous studies. Region-specific changes in the brain steady-state levels, and turnover rates of monoamines were detected 10 s after administration of a single repetitive TMS (rTMS) session. In the striatum and hippocampus, dopamine levels were increased by 25 +/- 1.5% and 18 +/- 0.8%, respectively, but were reduced in frontal cortex and decreased in the striatum and hippocampus in the TMS-treated rats with no change to the midbrain. TMS caused an increase in serotonin and 5-HIAA levels in the hippocampus but not in other brain regions examined in this study. The ability of TMS to induce behavioral and biochemical alterations similar to those of ECS may further support the potential role of TMS as an antidepressant treatment and bring us closer to the understanding of the mechanism of action of TMS.