Effectiveness of high‐frequency left prefrontal repetitive transcranial magnetic stimulation in patients with treatment‐resistant depression: A randomized clinical trial of 37.5‐minute vs 18.75‐minute protocol

Abstract

Aim Clinical trials and meta‐analyses have demonstrated the efficacy of high‐frequency repetitive transcranial magnetic stimulation (rTMS) over the left prefrontal cortex in treatment‐resistant depression. The aim of this study was to prospectively evaluate the effectiveness of the conventional 37.5‐minute vs 18.75‐minute rTMS protocol over the left prefrontal cortex in patients with treatment‐resistant depressive episode. Methods Thirty patients with treatment‐resistant depression or bipolar disorder depressive episode were randomized 1:1 to either 37.5‐minute or 18.75‐minute rTMS protocol groups. rTMS treatment was applied at 120% resting motor threshold with 10 Hz over the left prefrontal cortex. Treatment sessions were delivered for a total of 3000 pulses/d, 5 days a week, for 4‐6 weeks. Patients received a 75 trains with “4 sec on and 26 sec off” for 37.5 minutes or a 75 trains with “4 sec on and 11 sec off” for 18.75 minutes. Severity of depression was rated with the Quick Inventory of Depressive Symptomatology (QIDS) and Patient Health Questionnaire (PHQ‐9). Remission was defined as a total score of 5 or less on the QIDS. The primary outcome measure was to compare the remission rate between the both groups. Results Thirteen of 30 patients (43.3%) showed remission at week 6. There were no significant differences in the remission rate between the conventional 37.5‐ and 18.75‐minute protocol groups (46.7% and 40.0%, respectively). No seizures or treatment‐emergent mania/hypomania were occurred. Conclusion These findings suggest that, compared with the conventional one, rTMS with 18.75‐minute protocol might be equally effective and clinically beneficial in saving the treatment session length. Further well‐designed studies are needed.

Repetitive transcranial magnetic stimulation (rTMS) in bipolar disorder: A systematic review

“…Of the 10 sham‐controlled studies of rTMS for bipolar depression reported, 9 contained a sample of less than 20 subjects or had failed to find a statistically significant difference between active and sham rTMS at the end of the treatment course. Only one study showed a significant difference, and this was only for treatment response and not remission 36 . These findings appear to be in contrast with those of McGirr et al in a previous systematic review, which suggested the superiority for rTMS over sham 62 .…”

“…Twenty‐four of the included studies examined the efficacy of rTMS treatment in bipolar depressive episodes 28–39,43–54 …”

“…Notably, an upwards trend in response was found for rTMS treatment, suggesting that additional clinical benefit can be derived with more sessions. Kito et al evaluated the effectiveness of the conventional 37.5‐min high‐frequency (10 Hz) rTMS protocol ( n = 5) versus a shorter 18.75‐min ( n = 6) protocol in 11 treatment‐resistant bipolar depressive patients 36 . Similar rates of remission and response were found in both groups, suggesting that rTMS with the 18.75‐min protocol may be equally effective in treating depressive symptoms while reducing overall treatment session length.…”

“…All included trials reported random allocation, but only eight studies described the method used to generate the random sequence in detail and were thus rated “low risk” 29–31,44,45,52–54 . In seven studies, either the participants or researchers were not blinded, thus performance bias was rated as “high risk” 30,32,36,50,54–56 . The risk of attrition bias in one studies was rated as “high risk” because the research data were incomplete 46 .…”

“…However, their meta‐analysis only assessed anti‐depressive outcomes and did not explore the efficacy of rTMS in mania, mixed episodes, or as maintenance therapy. Furthermore, since its publication in 2016, several additional clinical trials ( n = 12) have explored the therapeutic benefits of rTMS in bipolar depression using new treatment protocols 28–39 . Although a recent review by Gold et al 40 discusses the application of rTMS across different stages of the bipolar disorder, we also sought to determine evidence for the use of rTMS in preventing recurrent mood episodes.…”