Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of adult major depressive episodes: A systematic review and network meta-analysis of 113 randomised clinical trials
Background: Non-surgical brain stimulation techniques have been applied as tertiary treatments in major depression. However, the relative efficacy and acceptability of individual protocols is uncertain. Our aim was to estimate the comparative clinical efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults.\n\nMethods: Embase, PubMed/MEDLINE and PsycINFO were searched up until May 8, 2018, supplemented by manual searches of bibliographies of recent reviews and included trials. We included clinical trials with random allocation to electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), accelerated TMS (aTMS), priming TMS (pTMS), deep TMS (dTMS), theta burst stimulation (TBS), synchronised TMS (sTMS), magnetic seizure therapy (MST) or transcranial direct current stimulation (tDCS) protocols or sham. Data were extracted from published reports and outcomes were synthesised using pairwise and network random-effects meta-analysis. Primary outcomes were response (efficacy) and all-cause discontinuation (acceptability). We computed odds ratios (OR) with 95% confidence intervals (CI). Remission and continuous post-treatment depression severity scores were also examined.\n\nResults: 113 trials (262 treatment arms) randomising 6,750 patients (mean age = 47.9 years; 59% female) with major depressive disorder or bipolar depression met our inclusion criteria. In terms of efficacy, 10 out of 18 treatment protocols were associated with higher response relative to sham in network meta-analysis: bitemporal ECT (OR=8.91, 95%CI 2.57-30.91), high-dose right-unilateral ECT (OR=7.27, 1.90-27.78), pTMS (OR=6.02, 2.21-16.38), MST (OR=5.55, 1.06-28.99), bilateral rTMS (OR=4.92, 2.93-8.25), bilateral TBS (OR=4.44, 1.47-13.41), low-frequency right rTMS (OR=3.65, 2.13-6.24), intermittent TBS (OR=3.20, 1.45-7.08), high-frequency left rTMS (OR=3.17, 2.29-4.37) and tDCS (OR=2.65, 1.55-4.55). Comparing active treatments, bitemporal ECT and high-dose right-unilateral ECT were associated with increased response. All treatment protocols were at least as acceptable as sham treatment.\n\nConclusion: We found that non-surgical brain stimulation techniques constitute viable alternative or add-on treatments for adult patients with major depressive episodes. Our findings also highlight the need to consider other patient and treatment-related factors in addition to antidepressant efficacy and acceptability when making clinical decisions; and emphasize important research priorities in the field of brain stimulation.\n\nO_LSTTreatment abbreviationsC_LSTECT = Electroconvulsive Therapy O_LIBF ECT = bifrontal ECT (1)\nC_LIO_LIBT ECT = bitemporal ECT (2)\nC_LIO_LIRUL ECT= right unilateral ECT O_LIH-RUL = high-dose RUL ECT (3)\nC_LIO_LILM-RUL = low to moderate-dose RUL ECT (4)\nC_LI\nC_LI\nrTMS = repetitive Transcranial Magnetic Stimulation O_LIHF-L rTMS = high-frequency rTMS of the left DLPFC (5)\nC_LIO_LIHF-R rTMS = high-frequency rTMS of the right DLPFC (6)\nC_LIO_LILF-R rTMS = low-frequency rTMS of the right DLPFC (7)\nC_LIO_LILF-L rTMS = low-frequency rTMS of the left DLPFC (8)\nC_LIO_LIBL rTMS = bilateral rTMS of the DLPFC (9)\nC_LI\ndTMS = deep Transcranial Magnetic Stimulation (10)\npTMS = priming Transcranial Magnetic Stimulation (11)\naTMS = accelerated Transcranial Magnetic Stimulation (12)\nsTMS = synchronised Transcranial Magnetic Stimulation (13)\nTBS = Theta Burst Stimulation O_LIiTBS = intermittent TBS of the left DLPFC (14)\nC_LIO_LIcTBS = continuous TBS of the right DLPFC (15)\nC_LIO_LIblTBS = bilateral TBS of the DLPFC (16)\nC_LI\nMST = Magnetic Seizure Therapy (17)\ntDCS = transcranial Direct Current Stimulation (18)\n\n\nKey points\n\nQuestion: What is the clinical efficacy and acceptability of non-surgical brain stimulation protocols for the acute treatment of major depressive episodes in adults?\n\nFindings: In this network meta-analysis, 10 out of 18 treatment protocols were associated with higher response rates relative to sham, most notably bitemporal and high-dose right unilateral electroconvulsive therapy. All treatment protocols were at least as acceptable as sham treatment.\n\nMeaning: Non-surgical brain stimulation techniques constitute viable alternative or add-on treatment strategies for adult patients with major depressive episodes.