More female patients and fewer stimuli per session are associated with the short-term antidepressant properties of repetitive transcranial magnetic stimulation (rTMS): a meta-analysis of 54 sham-controlled studies published between 1997-2013

Background: Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) appears to have short-term antidepressant properties. The aim of the current study was to update our previous meta-analysis and to investigate factors associated with the antidepressant properties of rTMS. Method: Following a systematic literature search conducted in Medline and PsycInfo, N=14 sham-controlled, parallel design studies (published after 2008 to August 2013) that had utilized rTMS of the DLPFC in major depression were included in the current meta-analysis. The sensitivity and moderator analyses also included data from N=40 studies (published in 1997-2008) from our previous meta-analysis. The effect size (Cohen's d) in each study was the standardized difference in mean depression scores (on Hamilton Depression Rating Scale, Beck Depression Inventory, Montgomery Asberg Depression Rating Scale) from baseline to final (after last -session) in rTMS compared to sham groups. Results: According to a random-effects model with inverse-variance weights, depression scores were significantly reduced after rTMS compared to sham in studies published from 2008-2013 based on N=659 patients (overall mean weighted d=-0.42, 95% confidence interval: -0.66, -0.18, P=0.001). Combining studies from our past and current meta-analyses (published in 1997-2013; N=54) revealed that depression was significantly reduced after left-fast (>1 Hz), right-slow (<= 1 Hz), and bilateral (or sequential) rTMS of DLPFC compared to sham. Significant antidepressant properties of rTMS were observed in studies with patients who were treatment resistant, unipolar (or bipolar), non-psychotic, medication-free (or started on antidepressants concurrently with rTMS). According to univariate meta-regressions, depression scores were significantly lower in studies with more female patients and fewer stimuli per session. There was little evidence that publication bias occurred in the analysis. Conclusion: According to this study, the largest meta-analysis to date, short-term antidepressant properties of rTMS are independent of concurrent antidepressants and might depend on sex and the number of stimuli per session.