Repetitive transcranial magnetic stimulation (rTMS) has been mainly studied as adjunctive treatment for drug-resistant patients. We assessed the effectiveness of rTMS started concomitantly with antidepressant medications in non-drug-resistant major depressive disorder patients. We also evaluated if, among the 3 antidepressants administered, one had a better synergy with rTMS.
In this 5-week, double-blind, randomized, sham-controlled study, we recruited 99 inpatients suffering from a major depressive episode (DSM-IV criteria). They were randomly assigned to receive venlafaxine, sertraline, or escitalopram in combination with a 2-week period of sham or active 15-Hz rTMS on the left dorso-lateral prefrontal cortex. Data were gathered from February 2004 to June 2005.
The active rTMS group showed a significantly faster reduction in Hamilton Rating Scale for Depression (HAM-D) scores compared with the sham group (p = .0029). The response and remission rates were significantly greater in the active rTMS group after the stimulation period (p = .002 and p = .003, respectively), but not at the endpoint. We found no significant difference in HAM-D score reduction among the 3 drugs administered, either in the active or in the sham group.
These findings support the efficacy of rTMS in hastening the response to antidepressant drugs in patients with major depressive disorder. The effect of rTMS seems to be unaffected by the specific concomitantly administered drug.
"Venlafaxine enhances cortical activation , whereas SSRIs depress paired-pulse facilitation , as revealed by TMS studies. Previous studies had investigated the combination of HF rTMS and venlafaxine; however, the results were mixed  . The mechanisms of action of intermittent or continuous HF and LF rTMS applied over the DLFPC are unclear, which limits the comparison of these approaches. "
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The aim of this study was to assess whether the combination of low frequency repetitive transcranial magnetic stimulation (rTMS) and venlafaxine (150-225 mg/day) is effective and safe for treatment-resistant unipolar depression (TRD).
In a multicenter (18 centers) randomized double blind controlled trial with three arms, 170 patients were allocated to receive active rTMS combined with active venlafaxine (n= 55), active rTMS combined with placebo venlafaxine (n= 60) or sham rTMS combined with active venlafaxine (n= 55). The patients received once daily sessions of active or sham 1Hz rTMS applied over the right dorsolateral prefrontal cortex (360 pulses/day delivered at 120% of the resting motor threshold) for two to six weeks; rTMS was combined with active or sham venlafaxine (mean dose: 179.0 ± 36.6 mg/day). The primary outcome was the number of patients who achieved remission, which was defined as an HDRS-17 score < 8.
We reported a similar significant antidepressant effect in the 3 groups (p< 10-6), with a comparable delay of action and a comparable number of remitters at the endpoint (28% in the combination group, 41% in the rTMS group and 43% in the venlafaxine group; p= 0.59).
Low frequency rTMS appears to be as effective as venlafaxine and as effective as the combination of both treatments for TRD. Because of its short session duration (the duration of one session was 8.5 minutes) and its safety, slow rTMS might be a useful alternative treatment for patients with TRD.
"Prefrontal repetitive transcranial magnetic stimulation (TMS) is a non-invasive well-tolerated alternative technique to pharmacological treatment, proposed in major depressive episodes (George and Post, 2011; Rumi et al., 2005), both in unipolar (Lam et al., 2008; Richieri et al., 2010; Schutter, 2010; Slotema et al., 2010) and in bipolar patients (Dell'Osso et al., 2009; Richieri et al., 2010; Tamas et al., 2007). TMS of either left or right dorsolateral prefrontal cortex (DLPFC) has in particular shown significant great overall response rates ( 450% decrease in symptom severity), in 30–64% patients in controlled studies (Anderson et al., 2007; Avery et al., 2006; Fitzgerald et al., 2006, 2009; George et al., 2010; Holtzheimer et al., 2010; Januel et al., 2006; Klein et al., 1999; Rossini et al., 2005). Recently, a large multisite trial reported effectiveness up to 58% in patients who had failed to an average of 2.5 previous antidepressant treatment trials (Carpenter et al., 2012). "
[Show abstract][Hide abstract] ABSTRACT: The effectiveness of repetitive transcranial magnetic stimulation (TMS) is well established while studies of maintenance TMS are lacking. We aim here to determine whether maintenance is associated to a decrease in the relapse rate of depression, following successful acute treatment.
We enrolled 59 consecutive patients with pharmacoresistant depression who have responded (>50% decrease in symptom severity) up to 6 weeks of acute TMS treatment. These patients received either 20 weeks of maintenance TMS (n=37) or no additional TMS treatment (n=22). We performed propensity adjusted-analysis to examine the association between the relapse rate over this 20-week period and maintenance TMS. Propensity analysis eliminated differences in baseline characteristics between patient with and without maintenance TMS and approximated the conditions of random site-of-treatment assignment.
At 20 weeks, relapse rate was significantly different between the two groups (p=0.004, propensity analysis): 14 patients in the maintenance TMS group (37.8%) vs. 18 in the non-maintenance TMS group (81.8%), with an adjusted Hazard Ratio (HR)=0.288 (0.124-0.669).
Maintenance TMS was associated with a significantly lower relapse rate in patients with pharmacoresistant depression in routine practice among responders.
"The number of patients was 274, mean age 44.7 years, and female to male ratio 183:91. Of note, authors found a larger antidepressant effect of TMS when compared with previous studies, both in low-frequency right-sided  and in high-frequency left-sided TMS [41, 42]. Of clinical interest, in relation to high-frequency, left-sided rTMS, there were significant differences between previous metanalytic studies and this meta-analysis, particularly when considering the number of sessions (10 vs 15). "
[Show abstract][Hide abstract] ABSTRACT: Major Depression (MD) and treatment-resistant depression (TRD) are worldwide leading causes of disability and therapeutic strategies for these impairing and prevalent conditions include pharmacological augmentation strategies and brain stimulation techniques. In this perspective, repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique with a favorable profile of tolerability which, despite being recently approved by the Food and Drug Administration (FDA) for the treatment of patients with medication-refractory unipolar depression, still raises some doubts about most effective parameters of stimulation.
A literature search was performed using PubMed for the years 2001 through February 2011 in order to review meta-analytic studies assessing efficacy and safety issues for rTMS in depressive disorders. Fifteen meta-analyses were identified and critically discussed in order to provide an updated and comprehensive overview of the topic with specific emphasis on potentially optimal parameters of stimulation.
First meta-analyses on the efficacy of rTMS for the treatment of MD and TRD have shown mixed results. On the other hand, more recent meta-analytic studies seem to support the antidepressant efficacy of the technique to a greater extent, also in light of longer periods of stimulation (e.g. > 2 weeks).
rTMS seems to be an effective and safe brain stimulation technique for the treatment of medication refractory depression. Nevertheless, further studies are needed to better define specific stimulation-related issues, such as duration of treatment as well as durability of effects and predictors of response.
Clinical Practice and Epidemiology in Mental Health 10/2011; 7:167-77. DOI:10.2174/1745017901107010167
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