Does rTMS hasten the response to escitalopram, sertraline, or venlafaxine in patients with major depressive disorder? A double-blind, randomized, sham-controlled trial.

Department of Psychiatry, School of Medicine, Vita-Salute University, San Raffaele Hospital, Via Stamina d'Ancona 20, 20127 Milan, Italy.
The Journal of Clinical Psychiatry (Impact Factor: 5.14). 01/2006; 66(12):1569-75. DOI: 10.4088/JCP.v66n1212
Source: PubMed

ABSTRACT 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.

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    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: Context 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). Method 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. Results 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). Conclusion 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.
    Brain Stimulation 11/2014; 7(6). DOI:10.1016/j.brs.2014.07.040 · 5.43 Impact Factor
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    ABSTRACT: Background The aim of the current meta-analysis was to investigate predictors of the durability of the antidepressant effect of high-frequency (>1 Hz) repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex in the absence of active maintenance treatment.Methods Following a systematic literature search of Medline and PsycInfo, N = 16 double-blind, parallel-design, randomized-controlled trials (RCTs) with high-frequency rTMS and inactive sham were included in the current meta-analysis. The effect size (Cohen's d) was the standardized mean difference in depression scores between sham and rTMS groups (baseline –follow-up). Meta-analysis was conducted according to a random-effects model with inverse-variance weights.ResultsMost RCTs reported only short follow-up phases of 2 weeks (range of 1–16 weeks). The antidepressant effect was observed during follow-up (in the absence of maintenance treatment) compared to baseline (overall mean weighted d = –.48, 95% confidence interval: –.70, –.25, P < .001, N = 16 RCTs with 495 patients). Such an antidepressant effect during follow-up was higher in RCTs with patients who were less severely ill, unipolar, nonpsychotic, treatment-resistant, and on antidepressants (either started with rTMS or continued at stable doses during acute treatment phases). The effect sizes were lower in RCTs with longer (8–16 weeks) compared to shorter (1–4 weeks) follow-up periods. The risk of publication bias was low.Conclusions High-frequency rTMS has only a small antidepressant effect during follow-up after short acute treatment (5–15 sessions) in the absence of active maintenance treatment. This effect depends on illness severity, decreases over time, and appears to be enhanced by antidepressants.
    Depression and Anxiety 02/2015; DOI:10.1002/da.22339 · 4.29 Impact Factor

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