Review article
Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: A systematic review and meta-analysis

https://doi.org/10.1016/j.pnpbp.2014.02.004Get rights and content

Highlights

  • ECT seemed more effective than and at least as acceptable as rTMS in the short term.

  • Especially in the presence of psychotic depression.

  • Less evidence suggested the short term benefits are maintained in the follow-up.

  • Will help clinicians to understand and apply ECT and rTMS better.

Abstract

Electroconvulsive therapy (ECT) is the most effective treatment of depression. During the last decades repetitive transcranial magnetic stimulation (rTMS), an alternative method using electric stimulation of the brain, has revealed possible alternative to ECT in the treatment of depression. There are some clinical trials comparing their efficacies and safeties but without clear conclusions, mainly due to their small sample sizes. In the present study, a meta-analysis had been carried out to gain statistical power. Outcomes were response, remission, acceptability and cognitive effects in depression. Following a comprehensive literature search that included both English and Chinese language databases, we identified all randomized controlled trials that directly compared rTMS and ECT for major depression. 10 articles (9 trials) with a total of 425 patients were identified. Methodological quality, heterogeneity, sensitivity and publication bias were systematically evaluated. ECT was superior to high frequency rTMS in terms of response (64.4% vs. 48.7%, RR = 1.41, p = 0.03), remission (52.9% vs. 33.6%, RR = 1.38, p = 0.006) while discontinuation was not significantly different between the two treatments (8.3% vs. 9.4%, RR = 1.11, p = 0.80). According to the subgroup analysis, the superiority of ECT was more apparent in those with psychotic depression, while high frequency rTMS was as effective as ECT in those with non-psychotic depression. The same results were obtained in the comparison of ECT with low frequency rTMS. ECT had a non-significant advantage over high frequency rTMS on the overall improvement in HAMD scores (p = 0.11). There was insufficient data on medium or long term efficacy. Both rTMS and ECT were well tolerated with only minor side effects reported. Results based on 3 studies suggested that specific cognitive domains such as visual memory and verbal fluency were more impaired in patients receiving ECT. In conclusion, ECT seemed more effective than and at least as acceptable as rTMS in the short term, especially in the presence of psychotic depression. This review identified the lack of good quality trials comparing the long-term outcome and cognitive effects of rTMS and ECT, especially using approaches to optimize stimulus delivery and reduce clinical heterogeneity.

Introduction

Electroconvulsive therapy (ECT), is a well-established and effective option for patients refractory or intolerant to pharmacotherapy (Janicak et al., 2002). It is the most effective short term treatment for severe major depression (MD) (Eranti et al., 2007) and has relatively high response and initial remission rates (Daly et al., 2001, Fink and Taylor, 2007, Husain et al., 2004, Lisanby, 2007, McClintock et al., 2011) especially in the presence of catatonia or psychosis (Bauer et al., 2002). Despite the high antidepressant efficacy of ECT (Eranti et al., 2007, Husain et al., 2004, Janicak et al., 1985, Janicak et al., 1989), a substantial number of depressed patients cannot tolerate ECT (Janicak and Martis, 1999) and the prospect of achieving prolonged remission with ECT is uncertain (McClintock et al., 2011, Sackeim et al., 2001). In some individuals, ECT adversely affects cognitive function, disrupting both new learning and remote memory, limiting its overall acceptability (Eranti et al., 2007). Additionally, the use of ECT is often limited by other issues such as need for anesthesia and seizure induction (Lisanby, 2007, Rose et al., 2003).

In the past decade, rTMS has emerged as an effective, non-invasive physical intervention applied to the left or right dorsolateral prefrontal cortex (DLPFC) for MD (Berlim et al., 2012, Fitzgerald et al., 2003, George et al., 2010, Lingeswaran, 2011, O'Reardon et al., 2007, Pallanti and Bernardi, 2009, Rosa and Lisanby, 2012). rTMS appears to target distributed brain networks that are central to the pathophysiology of depression (George and Post, 2011, Schutter, 2009) and is not followed by epileptic seizure activity. Low frequency rTMS (stimulation frequency usually equal to or less than 1 Hz) is thought to inhibit the targeted brain region, while high-frequency rTMS (usually 5–20 Hz) is considered to increase excitability (Pal et al., 2005, Rodriguez-Martin José et al., 2009, Rossi et al., 2009). Depending on the parameters employed, cortical inhibition or excitation resulting from rTMS can last for up to several hours after stimulation (Di Lazzaro et al., 2005, Pal et al., 2005). Compared to ECT, rTMS does not require general anesthesia, and does not give rise to memorizing difficulties or other serious side effects.

To date, several RCTs have compared the antidepressant efficacy and safety of rTMS and ECT (Eranti et al., 2007, Grunhaus et al., 2000, Grunhaus et al., 2003, Hansen et al., 2011, Janicak et al., 2002, Keshtkar et al., 2011, Pridmore et al., 2000, Rosa et al., 2006, Wang et al., 2004). While the antidepressant effects of rTMS are well established, its advantage over ECT continues to be controversial. Secondly, while it is generally accepted that rTMS protocols used for depression do not produce enduring cognitive disruption, it is unclear if this is a specific advantage when compared to ECT in severe depression. Further, sustaining short-term efficacy to achieve long-term remission is a crucial therapeutic goal in MD that is closely linked to social, occupational and economic outcomes (Kelsey, 2004). Given the enduring nature and severity of depression in patients who are referred to receive somatic interventions such as rTMS and ECT, comparing the utility of these interventions with regard to long-term clinical efficacy will potentially aid in complex treatment decisions. To this end we undertook a systematic review and meta-analysis of RCTs that compare rTMS and ECT for depression, with or without psychotic symptoms. We specifically focused on clinically meaningful outcomes namely response, remission and acceptability. We also investigated the differences in self-rated mood improvement, general mental state, cognitive function and adverse effects between the two interventions.

Section snippets

Search strategy

Relevant randomized controlled trials of rTMS and ECT in patients with depression that were published or made available electronically before November 26, 2013, were identified via Pubmed, Embase, Ovid (all database including Medline, the Cochrane library, PsycInfo and so on) EBSCO host, and major Chinese databases — Chongqing VIP Database (VIP), Wan Fang Database and Chinese National Knowledge Infrastructure (CNKI). The search strategies combined free-text searching with key words probing. Our

Results of literature search and characteristics of included studies

Of 658 articles obtained from the search, 10 articles (Dannon et al., 2002, Eranti et al., 2007, Grunhaus et al., 2000, Grunhaus et al., 2003, Hansen et al., 2011, Janicak et al., 2002, Keshtkar et al., 2011, Pridmore et al., 2000, Rosa et al., 2006, Wang et al., 2004) met the selection criteria and were thus included in further analysis. The study selection process is shown in Fig. 1. Two of the included articles (Dannon et al., 2002, Grunhaus et al., 2000) reported on the short-term and

Cognitive function

Five studies (Eranti et al., 2007, Grunhaus et al., 2000, Grunhaus et al., 2003, Hansen et al., 2011, Rosa et al., 2006) reported on cognitive performance. Of these, three (Eranti et al., 2007, Grunhaus et al., 2000, Grunhaus et al., 2003) reported on global cognitive performance as measured by Mini-Mental State Examination (MMSE). Pooled estimate from these studies revealed no difference in MMSE between rTMS and ECT (MD = 0.65; 95% CI =  0.51–1.82; p = 0.27, Supplementary Fig. 5). The heterogeneity

Side effects

Most of the studies reported the side effect profile of rTMS and ECT except Dannon et al. (2002) and Rosa et al. (2006). There were no significant adverse events (e.g., seizures) and generally only mild side effects were reported in the rTMS group. Four studies reported the numerical data about adverse events (Grunhaus et al., 2000, Grunhaus et al., 2003, Hansen et al., 2011, Janicak et al., 2002) of rTMS. Altogether, in rTMS froup, 17.0% (9/53, data from Grunhaus et al., 2000, Grunhaus et al.,

Psychotic symptoms

We also examined whether the RR for response and remission differed in trials that included patients with psychotic depression (Supplementary Figs. 6 and 7). Of the ten studies included in this meta-analysis, six included mixed samples of subjects with psychotic depression (Dannon et al., 2002, Eranti et al., 2007, Grunhaus et al., 2000, Hansen et al., 2011, Janicak et al., 2002, Pridmore et al., 2000), and two with only non-psychotic depression (Grunhaus et al., 2003, Rosa et al., 2006). Two

Discussion

In this systematic review and meta-analysis, 10 reports of 9 trials involving 425 participants were pooled. Our quantitative analysis found that ECT was more effective than rTMS for major depression, especially in short-term, particularly for patients with psychotic depression. There was less randomized evidence that the benefits are maintained in the long term. Furthermore, we found no significant between-group difference in all-cause discontinuation rates between the two treatments,

Acknowledgments

We would like to thank Stephanie Sampson for her helpful comments on a previous version of the manuscript.

This research was supported partly by grants from Research Leadership Development Plan of the City of Shanghai (XBR2011005) and Shanghai Key Laboratory of Psychotic Disorders (13dz2260500) for Chunbo Li, Wellcome Research Fellowship (WT096002/11/Z) for Lena Palaniyappan and Shanghai Health Bureau Youth Project (20124Y053, 2013SY003) for Juanjuan Ren and Jijun Wang.

References (50)

  • M.T. Berlim et al.

    A systematic review and meta-analysis on the efficacy and acceptability of bilateral repetitive transcranial magnetic stimulation (rTMS) for treating major depression

    Psychol Med

    (2012)
  • M.T. Berlim et al.

    Efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (rTMS) versus electroconvulsive therapy (ECT) for major depression: a systematic review and meta-analysis of randomized trials

    Depress Anxiety

    (2013)
  • T. Burt et al.

    Neuropsychiatric applications of transcranial magnetic stimulation: a meta analysis

    Int J Neuropsychopharmacol

    (2002)
  • J.J. Daly et al.

    ECT in bipolar and unipolar depression: differences in speed of response

    Bipolar Disord

    (2001)
  • V. Di Lazzaro et al.

    Theta-burst repetitive transcranial magnetic stimulation suppresses specific excitatory circuits in the human motor cortex

    J Physiol

    (2005)
  • R.A. Dunne et al.

    Systematic review and meta-analysis of bifrontal electroconvulsive therapy versus bilateral and unilateral electroconvulsive therapy in depression

    World J Biol Psychiatry

    (2012)
  • J. Eche et al.

    Low- vs high-frequency repetitive transcranial magnetic stimulation as an add-on treatment for refractory depression

    Front Psychiatry

    (2012)
  • S. Eranti et al.

    A randomized, controlled trial with 6-month follow-up of repetitive transcranial magnetic stimulation and electroconvulsive therapy for severe depression

    Am J Psychiatry

    (2007)
  • M. Fink et al.

    Electroconvulsive therapy: evidence and challenges

    JAMA

    (2007)
  • P.B. Fitzgerald et al.

    Transcranial magnetic stimulation in the treatment of depression: a double-blind, placebo-controlled trial

    Arch Gen Psychiatry

    (2003)
  • P.B. Fitzgerald et al.

    A randomized trial of rTMS targeted with MRI based neuro-navigation in treatment-resistant depression

    Neuropsychopharmacology

    (2009)
  • M.S. George et al.

    Daily left prefrontal repetitive transcranial magnetic stimulation for acute treatment of medication-resistant depression

    Am J Psychiatry

    (2011)
  • M.S. George et al.

    Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial

    Arch Gen Psychiatry

    (2010)
  • P.E. Hansen et al.

    Low-frequency repetitive transcranial magnetic stimulation inferior to electroconvulsive therapy in treating depression

    J ECT

    (2011)
  • L.L. Herrmann et al.

    Factors modifying the efficacy of transcranial magnetic stimulation in the treatment of depression: a review

    J Clin Psychiatry

    (2006)
  • Cited by (136)

    • Brain stimulation and other biological non-pharmacological interventions in mental disorders: An umbrella review

      2022, Neuroscience and Biobehavioral Reviews
      Citation Excerpt :

      Acceptability was significantly higher for ECT compared to AD (OR=2.94, 95 %CI=1.12–16.39), and for B-DLPFC rTMS compared to LF R-DLPFC rTMS (OR=2.43, 95 %CI=1.11–5.30) (Brunoni, Chaimani et al., 2017; UK ECT Review Group, 2003). No other difference in acceptability was found comparing ECT with rTMS (Chen et al., 2017; Ren et al., 2014), among different protocols of ECT (Mutz et al., 2019), and of rTMS (Brunoni, Chaimani et al., 2017; Chen et al., 2014; Mutz et al., 2019). In bipolar depressive episode, compared with inactive interventions, on primary outcome, the largest effect emerged for LT (SMD=0.43, 95%CI=0.04–0.82/GRADE=low) (Lam et al., 2020), followed by rTMS (SMD=0.30, 95 %CI=0.06–0.55/GRADE=low) (Tee and Au, 2020).

    • Affective Disorders

      2022, Comprehensive Clinical Psychology, Second Edition
    • Depression management and pharmacoepigenetics

      2022, Epigenetics of Stress and Stress Disorders
    View all citing articles on Scopus
    View full text