Effectiveness of Standard Sequential Bilateral Repetitive Transcranial Magnetic Stimulation vs Bilateral Theta Burst Stimulation in Older Adults With Depression

Abstract

ImportanceTreatment-resistant depression (TRD) is common in older adults. Bilateral repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex for 48 minutes has demonstrated efficacy in TRD. Theta burst stimulation (TBS), a newer form of rTMS, can also be delivered bilaterally using left intermittent TBS and right continuous TBS for only 4 minutes.ObjectiveTo establish the effectiveness and tolerability of TBS compared with standard rTMS in older adults with TRD.Design, Setting, and ParticipantsIn this randomized noninferiority trial with open treatment and blinded assessors, recruitment occurred between December 2016 and March 2020. The trial was conducted at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada and included outpatients 60 years and older with a diagnosis of depression, moderate severity, and nonresponse to 1 or more antidepressant trial of adequate dosage and duration or intolerance of 2 or more trials.InterventionsParticipants were randomized to receive a course of 4 to 6 weeks of either bilateral standard rTMS or TBS.Main Outcomes and MeasuresThe primary outcome measure was change in Montgomery-Åsberg Depression Rating Scale; secondary outcome measures included the 17-item Hamilton Rating Scale for Depression, Quick Inventory of Depressive Symptomatology (16-item) (self-report), and dropout rates. A noninferiority margin of 2.75 points was used for the primary outcome. All participants who attained the primary completion point of 4 weeks were analyzed.ResultsA total of 87 participants (mean [SD] age, 67.1 [6.7] years; 47 [54.0%] female) were randomized to standard bilateral rTMS and 85 (mean [SD] age, 66.3 [5.3] years; 45 [52.9%] female) to TBS, of whom 85 (98%) and 79 (93%) were assessed for the primary outcome, respectively, whereas tolerability was assessed in all randomized participants. In the rTMS group, 4 (4.6%) were American Indian, reported other, or preferred not to answer; 5 (5.8%) were Asian; and 78 (89.7%) were White. In the TBS group, 6 (7.1%) were Asian, 2 (2.4%) were Black or reported other, and 77 (90.3%) were White. Mean (SD) Montgomery-Åsberg Depression Rating Scale total scores improved from 25.6 (4.0) to 17.3 (8.9) for rTMS and 25.7 (4.7) to 15.8 (9.1) for TBS (adjusted difference, 1.55; lower 95% CI −0.67), establishing noninferiority for TBS. The all-cause dropout rates were relatively similar between groups (rTMS: 2 of 87 [2.3%]; TBS: 6 of 85 [7.1%]; P = .14; χ2 = 2.2).Conclusions and RelevanceIn older adults with TRD, bilateral TBS compared with standard bilateral rTMS achieved noninferior reduction in depression symptoms. Both treatments had low and similar dropout rates. Using TBS rather than rTMS could increase access to treatment several-fold for older adults with TRD.Trial RegistrationClinicalTrials.gov Identifier: NCT02998580

A pilot randomized sham controlled trial of bilateral iTBS for depression and executive function in older adults

“…In contrast, the sequential bilateral approach of inhibitory stimulation (1 Hz) to the right DLPFC and excitatory stimulation (10 Hz) to the left DLPFC has demonstrated efficacy with standard rTMS 54,55 and theta burst (continuous TBS right and iTBS left) 56 and has recently shown efficacy in older adults. 57,58 Notwithstanding the large effect in the sham group, the lower than expected depression response to active stimulation may reflect an unintended suppression of the antidepressant effects related to the excitatory stimulation of the right DLPFC.…”

Efficacy and safety of theta burst versus repetitive transcranial magnetic stimulation for major depressive disorder: a meta- analysis of randomized controlled trials

“…Notably, although three articles compared the e cacy of TBS and rTMS, they were not included because of their retrospective design [25,39,40]. After the selection procedure, nine eligible RCTs comparing the e cacy of TBS to rTMS for treating MDD were nally selected [17,23,[41][42][43][44][45][46][47]. Among them, Chen et al (2021) included two sets of comparable trials [43], namely, 10 Hz rTMS vs. low-intensity (80% RMT) TBS and 10 Hz rTMS vs. high-intensity (120% RMT) TBS.…”

“…Among the eight eligible RCTs, two were conducted in Canada [17,41], two in Australia [43,45], two in China [23,44], and one each in France [42], Britain [46],…”

Accelerated theta-burst transcranial magnetic stimulation of the bilateral dorsolateral prefrontal cortex in a patient with post-traumatic stress disorder and major depressive disorder: Case report

“…However, the effect of accelerated thetaburst stimulation (TBS) in patients with PTSD and depression remains unclear. Previous studies have demonstrated antidepressant effects of bilateral TBS (left sided iTBS + right sided cTBS) in the treatment of major depression (18)(19)(20). However, due to that patient's urgent clinical status, we needed to improve her condition rapidly.…”

“…Previous studies have demonstrated antidepressant effects of bilateral TBS (left sided iTBS + right sided cTBS) in the treatment of major depression ( 18 – 20 ). However, due to that patient's urgent clinical status, we needed to improve her condition rapidly.…”