Efficacy and acceptability of non-invasive brain stimulation for the treatment of adult unipolar and bipolar depression: A systematic review and meta-analysis of randomised sham-controlled trials

Abstract

26We examined the efficacy and acceptability of non-invasive brain stimulation in adult 27 unipolar and bipolar depression. Randomised sham-controlled trials of transcranial direct 28 current stimulation (tDCS), transcranial magnetic stimulation (TMS) and theta-burst 29 stimulation (TBS), without co-initiation of another treatment, were included. We analysed 30 response, remission and all-cause discontinuation rates, and depression severity scores. Fifty-31 four studies were included (N = 2,959, mean age = 44.94 years, 61.98% female). Response 32 rates demonstrated efficacy of high-frequency rTMS over the left DLPFC (OR = 3.94, 95% 33 CI [2.52; 6.15]), right-sided low-frequency rTMS (OR = 7.44, 95% CI [2.06; 26.83]) bilateral 34 rTMS (OR = 3.68, 95% CI [1.66; 8.13]), deep TMS (OR = 1.69, 95% CI [1.003; 2.85]), 35 intermittent TBS (OR = 4.70, 95% CI [1.14; 19.38]) and tDCS (OR = 4.32, 95% CI [2.02; 36 9.29]); but not for continuous TBS, bilateral TBS or synchronised TMS. There were no 37 differences in all-cause discontinuation rates. The strongest evidence was for high-frequency 38 rTMS over the left DLPFC. Intermittent TBS provides an advance in terms of reduced 39 treatment duration. tDCS is a potential treatment for non-resistant depression. 40 41 Keywords: transcranial magnetic stimulation, theta burst stimulation, transcranial direct 42 current stimulation, major depression, meta-analysis 43 BRAIN STIMULATION DEPRESSION META-ANALYSIS (≤ 1 Hz) stimulation inhibits neural firingRosa and Lisanby 7 . 62 63The rationale for using rTMS to treat depressive illness comes from clinical symptomatology 64 and neuroanatomy as well as neuroimaging studies indicating functional impairments in 65 prefrontal cortical and limbic regions 8 . In 2008, the US Food and Drug Administration (FDA) 66 approved the first rTMS device for the treatment major depressive disorder (MDD) in which 67 there was poor response to at least one pharmacological agent in the current episode 9 , and its 68 clinical utilisation has increased since 10 . 69 BRAIN STIMULATION DEPRESSION META-ANALYSIS 70As stimulation at high frequencies can be uncomfortable during the initial stimulation period, 71 low-frequency rTMS may minimise the occurrence of undesired side effects, namely 72 headaches and scalp discomfort, and may be associated with fewer adverse events, for 73 instance by lowering the risk for seizures 11 . 74 75 Bilateral applications of rTMS have also been developed: simultaneous stimulation over the 76 left and right DLPFC (rDLPFC) or stimulation over one side followed by stimulation of the 77 other side. These applications were hypothesised to be potentially additive or synergistic to 78 reinstate any imbalance in prefrontal neural activity 12 . Moreover, there may be a selective 79 unilateral response and the likelihood for a clinical response may increase by providing both 80 types of stimulation 13 . 81 82 Technical and methodological efforts to improve the antidepressant efficacy of TMS have led 83 to several alternative treatment pro...

Transcranial random noise stimulation for the acute treatment of depression: a randomized controlled trial

“…Interestingly, the present tRNS trial and Colleen K Loo et al (2018) have used the highest total number of sessions and strongest stimulation parameters, including current intensity, compared to other investigations of the antidepressant effects of transcranial electrical stimulation (Blumberger et al, 2012;Colleen K Loo et al, 2012;U Palm et al, 2012;Andre R Brunoni et al, 2013a;Bennabi et al, 2015), with both studies reporting no advantage of active stimulation over sham. Overall, studies show tDCS has antidepressant efficacy (Mutz et al, 2018), though one study suggested this may be less than escitalopram (Andre R Brunoni et al, 2017).…”

“…Applying a direct current between the electrodes, referred to as transcranial direct current stimulation (tDCS), has been demonstrated to have antidepressant effects in clinical trials (Colleen K Loo et al, 2012;Andre R Brunoni et al, 2013a;Andre R Brunoni et al, 2017). Recent meta-analyses of randomised, sham-controlled trials have found tDCS to be more effective than sham stimulation, with significantly higher remission and response rates as well as a greater reduction in depressive symptoms (André R. Brunoni et al, 2016;Mutz et al, 2018). As depression has increasingly been conceptualised as a disorder underpinned by disrupted neuroplasticity (Pittenger and Duman, 2008;Liu et al, 2017), cumulative changes to synaptic functioning may underlie the therapeutic effects observed in clinical trials of tDCS (Szymkowicz et al, 2016).…”

Association of BDNF, HTR2A, TPH1, SLC6A4, and COMT polymorphisms with tDCS and escitalopram efficacy: ancillary analysis of a double-blind, placebo-controlled trial

“…8 Nonetheless, tDCS has produced mixed outcomes in terms of antidepressant efficacy. [9][10][11][12] This may reflect a heterogeneous likelihood of response across participants. Therefore, identifying predictors of response may provide useful insights into tDCS, such as clarifying its mechanisms of action, predicting treatment outcomes, and designing better-tailored trials within the framework of precision psychiatry.…”

Time to remission analysis for major depressive disorder after repetitive transcranial magnetic stimulation (rTMS)

“…[3][4][5] Transcranial Magnetic Stimulation has proven to be efficacious at alleviating depression symptoms over a wide range of settings particularly for treatment-resistant cases of MDD. [6][7][8][9][10][11][12] The technology is widely utilized in clinical practice but the practical application to ethnically, financially, and geographically diverse patient groups with complex comorbidities require further characterization. [13][14][15] We recently examined the effectiveness of rTMS in combination with cognitive behavioral therapy (CBT) in the treatment of MDD using data derived from a retrospective review of medical records from patients with MDD undergoing rTMS therapy at a suburban tertiary psychiatric clinic, AwakeningsKC Clinical Neuroscience Institute (CNI).…”