CLINICAL INVESTIGATION OF THE EFFICACY OF PREFRONTAL RTMS ON THE REFRACTORY DEPRESSED PATIENTS IN TAIWAN

Abstract Background Repetitive transcranil magnetic stimulation (rTMS) has been developed as a novel tool for improving depression by delivering magnetic stimulation to the brain. rTMS has been approved to use for depression by Taiwan FDA since 2018. Over the past four years, we treated the patients with refractory depression (TRD) to investigate its clinical efficacy, response and remission rate and to search for the outcome predictors from clinical variables. Methods Using the Magstim machine as a stimulation tool, we applied it onto left prefrontal area of the brain in TRD patients, who included female 221 and male 115, aged 48.2 (+18.0) year; major depression 276 subjects (82%) and bipolar depression 60 subjects (18%). Their age-onset was 37.2 (+21.3) years and duration of illness was 13.2 (+11.2) years. Among them, 36% (n=120) and 64 (n=216) received standard TMS and theta burst stimulation (TBS) respectively. MARDRS mood scale rating was assessed at D0, D5, D10, D15, and D20. One-way ANOVA with repeated measures as well as pair t-test comparisons was performed for statistical analysis. Results All 218 subjects had completed one treatment course (10 times of stimulation), while 118 subjects of them received 2 treatment courses (20 times of stimulation). Primary outcome revealed a significant reduction of MADRS score from D0 (29.2 + 7.2), D5 (17.5 + 8.1) to D10 (14.1 + 9.5) with all significant mutual paired comparisons (all p<0.01). For the 2-course treatment group (n=118), similar results were observed with reduction of MADRS score from D0 (27.6 + 8.1) to D5 (17.2 + 8.9), D10 (13.6 + 9.6), D15 (9.1 + 6.2) to D20 (10.3 + 1.2) with all significant mutual paired t-test (all p<0.05), indicating that continuation stimulation for another 10 times may be more beneficial. Response rate (decreased MADRS score >=50% from D0) was found 55.2% on D10, while remission rate (MADRS <=11) was 46%. On D20, response rate was 74.5% while remission rate was 66.6%, Indicating that after 10 times stimulation, Pt still has room to improve mood symptoms during another 10 times of treatment. There were no differences between age (<50 vs.>=50) age onset (<50 vs.>=50), duration of illness (<5 years vs.>=5 years), gender, standard TMS and TBS, and diagnosis (MDD vs. BD). Furthermore, response on D5 &MINI social phobia may predict for D10 response of rTMS (OR: 8.8 and 2.3 higher than nonresponse). And comorbid with MINI GAD and Lower BL MADRS score may predict late response at D20 (OR: 8.56 &1.56 higher than with no GAD or more severe depressed subjects). Finally, depressed patients with early onset might have worse outcome than late onset for TMS treatment. Conclusion Either standard TMS or TBS showed equal efficacy on TRD patients with responder rate around 55% and remission rate of 46%. Treatment with a 2-course of rTMS is better than with one-course in the improvement of refractory depression. These patients with response on day 5 and comorbid GAD may be beneficial to TMS as greater as those without.