Patterns of response to repetitive transcranial magnetic stimulation (rTMS) in major depression: replication study in drug-free patients.
ABSTRACT Repetitive transcranial magnetic stimulation (rTMS) has been found to exert modest to moderate therapeutic effects in major depression, but mechanism of action and its clinical relevance have not been clarified yet. Previous trials have reported patterns of symptomatology predicting response to rTMS. As most patients also received concomitant antidepressant medication these response patterns may rather refer to combined treatment than rTMS alone. Thus, this study aims to replicate previous findings and explore patterns of response in drug-free patients.
In the Munich-Berlin Predictor Study data of 79 patients from two open clinical trials evaluating effects of high-frequency rTMS of the left dorsolateral prefrontal cortex were pooled. Previous models predicting the response to rTMS [Fregni, F., Marcolin, M.A., Myczkowski, M., Amiaz, R., Hasey, G., Rumi, D.O., Rosa, M., Rigonatti, S.P., Camprodon, J., Walpoth, M., Heaslip, J., Grunhaus, L., Hausmann, A., Pascual-Leone, A., 2006. Predictors of antidepressant response in clinical trials of transcranial magnetic stimulation. Int. J. Neuropsychopharmacol. 9, 641-654; Brakemeier, E.L., Luborzewski, A., Danker-Hopfe, H., Kathmann, N., Bajbouj, M., 2007. Positive predictors for antidepressive response to prefrontal repetitive transcranial magnetic stimulation (rTMS). J. Psychiatr. Res. 41, 395-403.] were systematically tested and new explorative regression analyses were conducted.
Of the 79 patients, 34.2% showed an antidepressant response. Previous models could not be validated. Explorative regression analysis revealed a significant model with therapy resistance, HAMD items 1 (depressed mood), and 2 (feelings of guilt) as negative and retardation as positive predictors.
No controlled study; specific statistical issues; sample size; differences concerning patient population and stimulation parameters between study sites.
In sum, this study does not confirm clinical valid and robust patterns being predictive for a response to rTMS in depression. The only exception is a high level of therapy resistance being associated with poor outcome. Future predictor studies should focus on large and homogenous samples of rTMS multicenter trials and include neurobiological variables.
SourceAvailable from: Karina Karolina Kedzior[Show abstract] [Hide abstract]
ABSTRACT: According to a narrative review of 13 meta-analyses (published up to 2010), repetitive transcranial magnetic stimulation (rTMS) has a moderate, short-term antidepressant effect in the treatment of major depression. The aim of the current study was to reanalyse the data from these 13 meta-analyses with a uniform meta-analytical procedure and to investigate predictors of such an antidepressant response. A total of 40 double-blind, randomised, sham-controlled trials with parallel designs, utilising rTMS of the dorsolateral prefrontal cortex in the treatment of major depression, was included in the current meta-analysis. The studies were conducted in 15 countries on 1583 patients and published between 1997-2008. Depression severity was measured using the Hamilton Depression Rating Scale, Beck Depression Inventory, or Montgomery Åsberg Depression Rating Scale at baseline and after the last rTMS. A random-effects model with the inverse-variance weights was used to compute the overall mean weighted effect size, Cohen's d. There was a significant and moderate reduction in depression scores from baseline to final, favouring rTMS over sham (overall d = -.54, 95% CI: -.68, -.41, N = 40 studies). Predictors of such a response were investigated in the largest group of studies (N = 32) with high-frequency (>1 Hz) left (HFL) rTMS. The antidepressant effect of HFL rTMS was present univariately in studies with patients receiving antidepressants (at stable doses or started concurrently with rTMS), with treatment-resistance, and with unipolar (or bipolar) depression without psychotic features. Univariate meta-regressions showed that depression scores were significantly lower after HFL rTMS in studies with higher proportion of female patients. There was little evidence for publication bias in the current analysis. Daily rTMS (with any parameters) has a moderate, short-term antidepressant effect in studies published up to 2008. The clinical efficacy of HFL rTMS may be better in female patients not controlling for any other study parameters.10/2014; 2(1):39. DOI:10.1186/s40359-014-0039-y
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ABSTRACT: One out of four patients with a psychiatric disorder does not tolerate or sufficiently respond to standard treatments, leading to impaired quality of life, significant morbidity and mortality, as well as high socioeconomic costs. There is increasing evidence that-apart from psychopharmacologic and psychotherapeutic interventions-targeted modulation of neural networks by brain stimulation techniques might serve as a third treatment modality. In the whole spectrum of treatment modalities, combined approaches are often used for difficult-to-treat patients. They may be superior strategies compared to monotherapy and could possible also include brain stimulation interventions. However, systematic research is lacking for the latter issue. Particularly, noninvasive brain stimulation (NIBS), e.g., transcranial direct current stimulation (tDCS) can be easily combined with psychotherapy approaches. Here, we introduce NIBS techniques for priming and augmenting psychotherapy, review preliminary data and propose a future research strategy. Interestingly, this strategy parallels the promising development in neurology and neurorehabilitation where tDCS is currently combined with functional training tasks to enhance motor or cognitive performance.European Archives of Psychiatry and Clinical Neuroscience 09/2014; DOI:10.1007/s00406-014-0540-6 · 3.36 Impact Factor
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ABSTRACT: -This chart review examined clinical, treatment parameter, and outcome data from 185 outpatients with medication-resistant major depression who received either 10 Hz (30 min) or intermittent theta burst (6 min) rTMS of the bilateral dorsomedial prefrontal cortex, under MRI guidance, at 120% resting motor threshold, in a single Canadian clinic (the Toronto Western Hospital) from April, 2011 to February, 2014.-There were no seizures or other serious adverse events over 7912 total runs of stimulation in 185 unique patients (10 Hz: 4274 runs, 2137 sessions, 98 patients; iTBS: 3638 runs, 1819 sessions, 87 patients). There were no significant differences between 10 Hz and iTBS patients in the rates of discontinuation for lack of response, adverse symptoms, or unspecified reasons.-Dichotomous outcomes did not differ significantly between groups (Response/remission rates: BDI-II: 10 Hz, 40.6%/29.2%; iTBS, 43.0%/31.0%. HamD17: 10 Hz, 50.6%/38.5%; iTBS, 48.5%/27.9%). On continuous outcomes, there was no significant difference between groups in pre-treatment or post-treatment scores, or percent improvement on either BDI-II of HamD17. Mixed-effects modelling revealed no significant group-by-time interaction on either measure.-Outcomes were non-normally distributed in both groups, with a trimodal distribution into non-responders, partial responders, and strong responders apparent on kernel density estimates of the distribution of outcomes in both groups on BDI-II and HamD17 measures.-Non-parametric comparisons of the cumulative distribution functions for the 10 Hz and iTBS groups also revealed no significant differences in outcomes on either BDI-II or HamD17 measures.-In terms of pace of improvement, mixed-effects models found no significant group by time interaction over the course of treatment, on either the BDI-II or HamD17 measures.-The results suggest that iTBS may be as safe and well-tolerated as 10 Hz stimulations requiring 5 times as many pulses and 5 times as much time to administer, while achieving equivalent outcomes. The implications of this finding for rTMS treatment costs and clinic capacities could be substantial. A randomized controlled trial comparing conventional 10 Hz stimulation to briefer iTBS protocols, at the conventional target in the left DLPFC, may be warranted.Brain Stimulation 11/2014; DOI:10.1016/j.brs.2014.11.002 · 5.43 Impact Factor