Supplementary Online ContentSupplementary Online Content . Brunoni AR, Chaimani A, Moffa AH, et al. Repetitive transcranial magnetic stimulation for the acute treatment of major depressive

Supplementary Online Content

Brunoni AR, Chaimani A, Moffa AH, et al. Repetitive transcranial magnetic stimulation for the acute treatment of major depressive episodes: a systematic review with network meta-analysis [published online December 28, 2016]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2016.3644

eAppendix 1. Search strategy

eAppendix 2. Risk of bias assessment

eTable 1. Characteristics of the 81 studies included in the meta-analysis.

eTable 2. Relative odds ratios (OR) with 95% confidence intervals (CI) estimated from standard pairwise meta-analysis for every available direct comparison between the 9 interventions with respect to response.

eTable 3. Relative odds ratios (OR) with 95% confidence intervals (CI) estimated from standard pairwise meta-analysis for every available direct comparison between the 9 interventions with respect to acceptability.

eTable 4. Relative odds ratios (OR) with 95% confidence intervals (CI) estimated from standard pairwise meta-analysis for every available direct comparison between the 9 interventions with respect to remission.

eTable 5. Relative odds ratios estimated from the network meta-analysis comparing every pair of the 9 interventions with respect to remission (lower triangle) and acceptability (upper triangle).

eTable 6. Results of the side-splitting approach for inconsistency for all outcomes.

eTable 7. Relative odds ratios estimated from the sensitivity analysis without studies at high risk of overall bias comparing every pair of the 9 interventions with respect to response (lower triangle) and acceptability (upper triangle).

eTable 8. Relative odds ratios estimated from the sensitivity analysis using only studies on primary use of rTMS (i.e. on treatment resistant patients and as an add-on intervention) comparing every pair of the 9 interventions with respect to response (lower triangle) and acceptability (upper triangle).

eTable 9. Relative odds ratios estimated from the sensitivity analysis using only studies with at least 15 sessions comparing every pair of the 9 interventions with respect to response (lower triangle) and acceptability (upper triangle).

eFigure 1. Contribution matrices for (A) response and (B) acceptability.

eFigure 2. (A) network diagram and (B) contribution matrix for remission.

eFigure 3. Boxplots and histograms showing the distribution of four potential effect modifiers (mean age, baseline severity, percentage of females, number of sessions) across the available direct comparisons.

eFigure 4. Rankograms for (A) response and (B) acceptability. The horizontal axes contain the possible ranks and the vertical axes contain the probabilities for each intervention of achieving every rank.

© 2016 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ by a Non-Human Traffic (NHT) User on 04/01/2020

eFigure 5. Relative ranking of the 9 different rTMS strategies for response (horizontal axis) and acceptability (vertical axis) based on the surface under the cumulative ranking curve (SUCRA). Different colours represent different groups of interventions based on their performance on both outcomes jointly.

eFigure 6. (A) Rankograms and (B) cumulative rankograms for remission.

eFigure 7. Forest plots showing the inconsistency factors (IF) and the respective 95% CI (truncated to 0) for every loop of the (A) response, (B) acceptability and (C) remission network

eFigure 8. Comparison-adjusted funnel plots for all comparisons between an active intervention and sham for (A) response, (B) acceptability and (C) remission.

eFigure 9. Bar-graphs showing the percentage of information coming from studies at low (green), unclear (yellow) or high (red) risk of overall bias for (A) response and (B) acceptability for every network estimate and for the entire network.

This supplementary material has been provided by the authors to give readers additional information about their work.



eAppendix 1

SEARCH STRATEGY

• No language restrictions were applied.

• Cochrane Central Register of Controlled Trials (CENTRAL) through October 1st,

2016

#1: transcranial magnetic stimulation:ti,ab,kw or transcranial magnetic:ti,ab,kw in

Trials (Word variations have been searched)

#2: depression:ti,ab,kw or "major depression":ti,ab,kw or "major depressive

disorder":ti,ab,kw or "major depressive episode":ti,ab,kw (Word variations have been

searched)

#3: #1 and #2

• EMBASE through October 1st, 2016 (via OVID)

(random$.tw. or placebo$.mp. or double-blind$.tw. or trial.ti,ab,kw) and (magnetic

stimulation.ti,ab,kw or rtms.ti,ab,kw or transcranial magnetic.ti,ab,kw) and

depress$.ti,ab,kw

• PsycInfo through October 1st, 2016 (via OVID)

(random$.tw. or placebo$.mp. or double-blind$.tw. or trial.ti,ab,kw) and (magnetic

stimulation.ti,ab,kw or rtms.ti,ab,kw or transcranial magnetic.ti,ab,kw) and

depress$.ti,ab,kw

• Pubmed/MEDLINE through October 1st, 2016

("randomized controlled trial"[PT] OR ((randomized[TIAB] OR randomised[TIAB])

AND controlled[TIAB] AND trial[TIAB])) AND (“magnetic stimulation”[TIAB] OR

rTMS[TIAB]) AND depress*[TIAB]



• Web of Science through October 1st, 2016

1: TI=(random* OR placebo OR double-blind OR trial)

2: TS=depress*

3: TI=(rTMS OR repetitive transcranial OR transcranial magnetic)

4: #1 AND #2 AND #3

We also checked reference lists from previous meta-analyses, systematic reviews and

consensus papers 1-7 and electronically contacted experts in the field.



eAppendix 2

RISK OF BIAS ASSESSMENT We adopted the following general rules to decide on risk of bias:

• Randomization (Selection bias)

Low risk: randomization method described.

Unclear risk: randomization method not described.

High risk: wrong randomization method adopted (in this case the study would be excluded as

we only included randomized clinical trials).

• Allocation concealment (Selection bias)

Low risk: allocation method described (e.g., sealed envelopes).

Unclear risk: allocation method not described.

High risk: allocation was not concealed.

• Blinding of participants and personnel (Performance bias)

Low risk: If using sham coil: blinding should be described. If using angled coil or two active

interventions: blinding integrity of participants should be successful and; for it should be

described that the rTMS applier did not communicate with the staff.

Unclear risk: For sham coil: blinding is not properly described. If using angled coil or two

active interventions: blinding integrity not tested, communication between rTMS applier and

staff not described.

High risk: for angled coil/two active interventions: rTMS appliers also evaluated patients or

communicated with the staff.

• Blinding of outcome assessment (Detection bias)

Low risk: study describes that evaluator was blinded. Unclear risk: study does not describe whether evaluator was blinded.



High risk: evaluator was not blinded to the assigned intervention. (in this case the study will

be excluded)

• Incomplete outcome data (Attrition bias)

Low risk: no attrition or attrition was properly described with reasonable reasons for missing

data.

Unclear risk: attrition was not sufficiently described. High risk: attrition was unbalanced; analyses were carried out only or primarily in patients

who complied to the protocol (i.e., “good adherers”).

• Selective outcome reporting (Reporting bias)

Low risk: all outcomes are reported. Unclear risk: not all outcomes are reported; however the primary outcomes are reported.

High risk: at least one primary outcome is not reported.

• Overall risk of bias Low risk: low risk in all domains or low risk in all domains except for unclear risk in

allocation bias.

Unclear risk: at least one unclear risk of bias domain, except for allocation bias.

High risk: at least one high risk of bias in any domain

QUALITY ASSESSMENT OF THE INCLUDED ARTICLES

Aut

hor

Sequ

ence

gen

erat

ion

Allo

catio

n C

once

alm

ent

Blin

ding

par

ticip

ants

an

d pe

rson

nel

Blin

ding

of o

utco

me

asse

ssm

ent

Inco

mpl

ete

outc

ome

data

Sele

ctiv

e ou

tcom

e re

porti

ng

Ove

rall

risk

of b

ias

Aguirre 2011 Unclear Unclear Unclear Low Low Low Unclear Anderson 2007 Unclear Low Unclear Low Low Low Unclear Avery 2006 Low Unclear Low Low Low Low Low Baeken 2013 Low Unclear Unclear Low Low Low Unclear



Bakim 2012 Low Unclear Unclear Low Low Low Unclear Berman 2000 Unclear Unclear Low Low High Low High Blumberger 2012 Low Low Low Low Low Low Low Blumberger 2016 Low Unclear Low Low Low Low Low Boutros 2002 Low Unclear Low Low Low Low Low Bretlau 2008 Unclear Unclear Unclear Unclear Low Low Unclear Brunelin 2014 Low Low Unclear Low Low Low Unclear Chen 2013 Unclear Unclear Low Low Low Low Unclear Chistyakov 2015 Unclear Unclear Low Low Low Low Unclear Concerto 2015 Unclear Unclear Unclear Unclear Low Low Unclear DellOsso 2015 Unclear Unclear High Unclear High Low High Duprat 2016 Unclear Unclear Unclear Low Low Low Unclear Eche 2012 Unclear Unclear Unclear Low Low Low Unclear Eschweiler 2000 Unclear Unclear Low Low Low Low Unclear Fitzgerald 2003 Unclear Low Low Low Low Low Unclear Fitzgerald 2006 Low Low Low Low Low Low Low Fitzgerald 2008 Low Unclear Unclear Low Low Low Unclear Fitzgerald 2009 Low Low Low Low Low Low Low Fitzgerald 2011 Low Unclear Low Low Low Low Low Fitzgerald 2012 Low Low Low Low Low Low Low Fitzgerald 2013 Low Unclear High Unclear Low Low High Fitzgerald 2016 Low Unclear Low Low Low Low Low Garcia-Anaya 2011 Unclear Unclear Low Low Unclear Low Unclear Garcia-Toro 2001a Unclear Unclear Unclear Low Unclear Low Unclear Garcia-Toro 2001b Unclear High Unclear Low Unclear Low High Garcia-Toro 2006 Unclear High Unclear Low Low Low High George 1997 Unclear Unclear Unclear Low Low Unclear Unclear George 2000 Unclear Unclear Low Low Low Low Unclear George 2010 Low Unclear Low Low Low Low Low Hansen 2004 Low Unclear Low Low Unclear Low Unclear Hausmann 2004 Unclear Unclear Unclear Low Low Low Unclear Hernandez-Ribas 2013

Unclear Unclear Unclear Low Unclear Low Unclear

Herwig 2003 Unclear Unclear Unclear Low Unclear Low Unclear Herwig 2007 Low Unclear Unclear Low Low Low Unclear Holtzheimer 2004 Unclear Unclear Unclear Low Low Low Unclear Hoppner 2003 Low Unclear Unclear Unclear Unclear Low Unclear Hu 2016 Unclear Unclear Unclear Unclear Low Low Unclear Huang 2012 Low Unclear Unclear Low Low Low Unclear Isenberg 2005 Unclear Unclear High Unclear Unclear Low High Jakob 2008 Unclear Unclear Low Low Low Low Unclear Januel 2006 Low Unclear Unclear Low High Low High Karamustafalioglu 2010

Unclear Unclear Unclear Unclear Unclear Unclear Unclear

Kauffmann 2004 Unclear Unclear Unclear Low Low Low Unclear Kazemi 2016 Low Unclear Low Low Low Low Low Klein 1999 Low Unclear Unclear Low Low Low Unclear Koerselman 2004 Unclear Unclear Low Low Low Low Unclear



Kreuzer 2015 Low Unclear Low Low High Low High Krstic 2014 Unclear Unclear Unclear Low Low Low Unclear Leuchter 2015 Low Unclear Low Low Low Low Low Levkovitz 2015 Low Low Low Low Low Low Low Li 2014 Unclear Unclear Unclear Low Low Low Unclear Lingeswaran 2011 Low Unclear Low Low Unclear Low Unclear Loo 1999 Unclear Unclear Low Low Low Low Unclear Loo 2003 Unclear Unclear Unclear Low Low Low Unclear Loo 2007 Low Unclear Unclear Low Low Low Unclear Martinot 2010 Low Low Low Low Low Low Low McDonald 2006 Unclear Unclear Unclear Low Low Low Unclear Mogg 2008 Low Low Low Low Low Low Low Mosimann 2004 Unclear Unclear Unclear Low Low Low Unclear Nahas 2003 Low Unclear Low Low Low Low Low O’Reardon 2007 Unclear Unclear Low Low Low Low Unclear Padberg 2002 Unclear Unclear Unclear Low Low Low Unclear Pallanti 2010 Low Low Unclear Low Low Low Unclear Plewnia 2014 Low Unclear Unclear Low Unclear Low Unclear Prasser 2014 Unclear Unclear Unclear Low Low Low Unclear Rossini 2005a Low Unclear Low Low Low Low Low Rossini 2005b Low Unclear Unclear Low Low Low Unclear Rossini 2010 Unclear Unclear High Unclear Low Low High Rumi 2005 Unclear Unclear Unclear Low Unclear Low Unclear Speer 2014 Unclear Unclear Unclear Low Low Low Unclear Stern 2007 Unclear Unclear Unclear Low Low Low Unclear Su 2005 Unclear Unclear Unclear Low Low Low Unclear Szuba 2001 Unclear Unclear Low Low Low Low Unclear Triggs 2010 Unclear Unclear Low Low Low Low Unclear Zhang 2011 Low Unclear Unclear Low Low Low Unclear Zheng 2010 Unclear Unclear Unclear Unclear Unclear Low Unclear Zheng 2015 Unclear Unclear Unclear Low Low Low Unclear

Random sequence generation Low risk Thirty-five studies adequately described the method of sequence generation (Avery 2006, Baeken 2013, Bakim 2012, Blumberger 2012, Blumberger 2016, Boutros 2002, Brunelin 2014, Fitzgerald 2006, Fitzgerald 2008, Fitzgerald 2009, Fitzgerald 2011, Fitzgerald 2012, Fitzgerald 2013, Fitzgerald 2016, George 2010, Hansen 2004, Herwig 2007, Hoppner 2003, Huang 2012, Januel 2006, Kazemi 2016, Klein 1999, Kreuzer 2015, Leuchter 2015, Levkovitz 2015, Lingeswaran 2011, Loo 2007, Martinot 2010, Mogg 2008, Nahas 2003, Pallanti 2010, Plewnia 2014, Rossini 2005a, Rossini 2005b, Zhang 2011).

Unclear risk The remainder (46 studies) did not provide details and were at unclear risk of selection bias.

Allocation concealment Low risk



Eleven studies were rated at low risk of bias as they had adequate allocation concealment (Anderson 2007, Blumberger 2012, Brunelin 2014, Fitzgerald 2003, Fitzgerald 2006, Fitzgerald 2009, Fitzgerald 2012, Levkovitz 2015, Martinot 2010, Mogg 2008, Pallanti 2010)

High risk of bias Two studies (Garcia -Toro 2006, Garcia-Toro-JNP 2001) allocated deliberately the left- handed participants to the sham rTMS and were rated at high risk of bias.

Unclear risk of bias The remainder (68 studies) had unclear allocation concealment.

Blinding participants and personnel Low risk of bias Thirty-three studies adequately described the blinding of participants and personnel (Avery 2006, Berman 2000, Blumberg 2012, Blumberg 2016, Boutros 2002, Chen 2013, Chistyakov 2015, Eschweiler 2000, Fitzgerald 2003, Fitzgerald 2006, Fitzgerald 2009, Fitzgerald 2011, Fitzgerald 2012, Fitzgerald 2016, Garcia-Anaya 2011, George 2000, George 2010, Hansen 2004, Jakob 2008, Kazemi 2016, Koerselman 2004, Kreuzer 2015, Leuchter 2015, Levkovitz 2015, Lingeswaran 2011, Loo 1999, Martinot 2010, Mogg 2008, Nahas 2003, O’Reardon 2007, Rossini 2005a, Szuba 2001, Triggs 2010) and had a low risk of performance bias.

High risk of bias These studies had a high risk of bias for the following reasons: Fitzgerald 2013 (priming + rTMS vs. no sham-priming) and Rossini 2010, Isenberg 2005, Dell’Osso 2015 (compared HF-left vs. LF-right without sham on the opposite hemisphere to keep personnel blinded).

Unclear risk of bias The other 44 studies had unclear risk of performance bias as the method of blinding participants and personnel was not adequately described

Blinding of outcome assessment Low risk of bias Seventy-one studies had a low risk of detection bias as the raters were adequately blinded.

Unclear risk of bias Bretlau 2008, Concerto 2015, Hoppner 2003, Zheng 2010 did not adequately describe blinding of outcome assessment. Dell’Osso 2015, Fitzgerald 2013, Hu 2016, Isenberg 2005, Karamustafalioglu 2010, Rossini 2010 also did not describe methods to maintain the outcome assessment blinded.

Incomplete outcome data Low risk of bias

Sixty-four studies had a low risk of attrition bias, because: • 13 studies were analysed on an intention-to-treat basis (Anderson 2007, Avery 2006,

Blumberger 2012, Brunelin 2014, Duprat 2016, Fitzgerald 2009, Fitzgerald 2006, George 2010, Herwig 2007, Huang 2012, Loo 2007, Mogg 2008, Rossini 2005b)



• 31 studies adequately reported and dealt with attrition (Aguirre 2011, Baeken 2013, Bakim 2012, Blumberger 2016, Boutros 2002, Bretlau 2008, Chen 2013, Chistyakov 2015, Fitzgerald 2008, Fitzgerald 2013, Fitzgerald 2003, Fitzgerald 2011, Fitzgerald 2012, Fitzgerald 2016, George 2000, Haussman 2004, Holtzheimer 2004, Hu 2016, Klein 1999, Koerselman 2004, Loo 2003, Martinot 2010, McDonald 2006, Leuchter 2015, Levkovitz 2015, O’Reardon 2007, Padberg 2002, Prasser 2014, Rossini 2005a, Speer 2014, Zhang 2011).

• 20 studies reported no losses to follow-up (Concerto 2015, Eche 2012, Eschweiler 2000, Garcia-Toro 2006, George 1997, Jakob 2008, Kauffmann 2004, Kazemi 2016, Krstic 2014, Li 2014, Loo 1999, Mosimann 2004, Nahas 2003, Pallanti 2010, Rossini 2010, Stern 2007, Su 2005, Szuba 2001, Triggs 2010, Zheng 2015).

High risk of bias Two studies had a very high attrition rate (Berman 2000, Januel 2006), and two studies excluded the dropouts participants from analysis (Kreuzer 2015, Dell’Osso 2015).

Unclear risk of bias

Thirteen studies had an unclear risk of attrition bias because reasons for loss to

follow-up or the handling of missing data were not consistently indicated or were unreported (Garcia-Anaya 2011, Garcia-Toro-JNNP 2001, Garcia-Toro-JAD 2001, Hansen 2004, Hernandez-Ribas 2013, Herwig 2003, Hoppner 2003, Isenberg 2005, Karamustafalioglu 2010, Lingerswaran 2011, Plewnia 2014, Rumi 2005, Zheng 2010).

Selective reporting

Low risk of bias Seventy-nine studies had a low risk of reporting bias as they fully reported all the primary clinical outcomes.

Unclear risk of bias Two studies (George 1997, Karamustafalioglu 2010) had an unclear risk ok bias.

Overall risk of bias Low risk of bias Seventeen studies had low overall risk of bias (Avery 2006, Blumberger 2012, Blumberger 2016, Boutros 2002, Fitzgerald 2006, Fitzgerald 2009, Fitzgerald 2011, Fitzgerald 2012, Fitzgerald 2016, George 2010, Kazemi 2016, Leuchter 2015, Levkovitz 2015, Martinot 2010, Mogg 2008, Nahas 2003 and Rossini 2005a).

High risk of bias



9 studies had high overall risk of bias (Berman 2000, Dell’Osso 2015, Fitzgerald 2013, Garcia -Toro 2006, Garcia-Toro-JNP 2001, Isenberg 2005, Januel 2006, Kreuzer 2015, Rossini 2010).

The remainder (55 studies) had unclear overall risk of bias.



eTable 1. Characteristics of the 81 included studies in the network meta-analysis.

Author

Group 1

Group 2

Group 3

Sample size

Interventi on

%

Fem ales

Mean Age

Only TRD/fa

iled trials

DLPF C

positio n

Group 1

Group 2

Group 3

Sessi ons

Hz

% MT

Total pulses

Hz

% MT

Total pulses

Sham method

Aguirre et al., 20118

LF

Sham

34

Add-on

67

47.5

Yes/1

5 cm

20

1

110

24000

Sham

Anderson et al., 20079

HF

Sham

25

Add-on

64

47

Yes/nd

5 cm

12

10

110

12000

Sham

Avery et al., 200610

HF

Sham

68

Mono

56

44.2

Yes/2

5 cm

15

10

110

24000

Angled

Baeken et al., 201311

aTMS

Sham

21

Add-on

61

49

Yes/2

NN

20

20

110

31200

Angled

Bakim et al., 201212

HF

Sham

23

Add-on

88

42.5

Yes/2

5 cm

30

20

110

24000

Angled

Berman et al., 2000 13

HF

Sham

20

Add-on

30

42.3

Yes/1

5 cm

10

20

80

8000

Angled

Blumberger et al., 2012 14

HF

Bi

Sham

68

Add-on

58

51

Yes/2

5 cm

15

10

110

21750

1/10

100/120

6300/15000

Angled

Blumberger et al., 201615

HF

Bi

Sham

121

Add-on

64

47

Yes/2

NN

15

10

120

31500

1/10

120 / 120

9000/22500

Angled

Boutros et al., 200216

HF

Sham

21

Add-on

24

50.6

Yes/2

5 cm

10

20

80

8000

Angled

Bretlau et al., 2008 17 HF Sham 49 Aug 62 55.4 Yes/1

5 cm

15

8

90

19200

Others

Brunelin et al., 201418

LF

Sham

101

Aug

60

54

Yes/1

6 cm

10-30

1

120

3600-10800

Sham

Chen et al., 2013 19 HF Sham 21 Add-on 54 45.8 Yes/2 5 cm 10

20

90

8000

Angled

Chistyakov et al., 201520

TBS

Sham

29

Add-on

62

51.8

No

5 cm

10

@

100*

@

Sham

Concerto et al., 2015 21 HF Sham 30 Add-on 43 52 Yes/3

5 cm

20

10

120

60000

Angled

Dell’Osso et al., 2015 22

HF

LF

33

Add-on

49

50.9

Yes/1

5 cm

20

10

80

15000

1

110

16500

.

Duprat et al., 2016 23 TBS Sham 50 Mono . . Yes/1 NN 20

!!!!

110

32400

Others

Eche et al., 2012 24 LF HF 14 Aug 57 48.1 Yes/1 5 cm 20

1

100

2400

10

100

40000

.

Eschweiler et al., 2000 25 HF Sham 12 Add-on . . Yes/1

5 cm

10

10

90

20000

Angled

Fitzgerald et al., 2011 26

LF

Bi

142

Add-on

67

47.2

Yes/2

6 cm

20

1

110

18000

1 / 10

110

18000

.

Fitzgerald et al., 200327

HF

LF

Sham

60

Add-on

47

45

Yes/2

5 cm

10

10

100

10000

1

100

3000

Angled




Bi

Sham

50

Add-on

62

45.5

Yes/2

5 cm

10

1 / 10

110 / 100

4200 / 7500

Angled


pTMS

LF

60

Add-on

58

45.2

Yes/2

5 cm

10

%

%

%

1

110

9000

Angled

Fitzgerald et al., 2009 30

HF

LF

27

Add-on

40

44

Yes/2

5 cm

15

10

100

22500

1

110

10800

.


HF

Bi

Sham

66

Add-on

56

42.9

Yes/2

NN

15

10

120

22500

1/10

120

13500/ 22500

Angled


Bi

pTMS

179

Add-on

69

47.3

Yes/2

6 cm

20

1/10

110/110

18000/15000

%

%

%

.


Bi

Sham

46

Add-on

59

47.9

Yes/2

NN

20

1/10

110/110

20000/20000

Angled

García-Anaya et al., 2011 34

HF LF 20 . 70 31.8 No 5 cm 15

5

100

22500

1

100

13500

.

Garcia-Toro et al, 200635

Bi

Sham

30

Add-on

50

49

Yes/2

EEG

10

1 / 20

110

18000 / 12000

Angled

Garcia-Toro et al., 2001 36

HF

Sham

40

Add-on

43

50.7

Yes/2

5 cm

10

20

90

12000

Angled

Garcia-Toro et al., 2001 37

HF

Sham

28

Aug

54

44.1

No

5 cm

10

20

90

12000

Angled

George et al., 199738 HF Sham 12 . 92 41.8 . 5 cm 10

20

80

8000

Angled

George et al., 2000 39

HF

Sham

30

Mono

63

44.5

No

5 cm

10

5/20

100

16000

Angled

George et al., 2010 40

HF

Sham

199

Mono

57

47.1

Yes/1

MRI

15

10

120

45000

Sham

Hansen et al., 2004 41 HF Sham 13 Add-on 31 44.4 No 5 cm 15

10

90

30000

Angled

Hausmann et al., 2004 42 HF Bi Sham 41 Aug 61 46.5 No MRI 10

20

100

20000

1/20

120/100

26000/ 20000

Others

Hernandez-Ribas et al., 2013 43

HF

Sham

21

Add-on

76

46

Yes/1

5 cm

15

15

100

22500

Angled

Herwig et al., 200344

HF

Sham

25

Add-on

60

44.7

No

NN

10

15

110

30000

Others

Herwig et al., 200745

HF

Sham

127

Aug

60

49.5

Yes/2

EEG

15

10

110

30000

Angled

Holtzheimer et. al.,200446

HF Sham 15 Mono 49 43.7 Yes/2 5 cm 10

10

110

16000

Angled

Hoppner et al., 200347

LF

Sham

20

Add-on

75

54

No

5 cm

10

1

110

1200

Angled

Hu et al., 2016 48 LF HF Sham 38 Aug 51 26.4 No 5 cm 20

1

80

24000

10

80

24000

Angled

Huang et al., 201249

HF

Sham

60

Aug

70

32

No

5 cm

10

10

90

8000

Angled

Isenberg et al., 2005 50

HF

LF

28

Add-on

73

49.4

Yes/2

5 cm

20

20

80

40000

1

110

2400

.



Jakob et al., 2008 51 HF HF Sham 36 Add-on 50 . No . 10

20

100

20000

50

100

20000

Sham

Januel et al., 2006 52

LF

Sham

27

Mono

78

37.8

Yes/2

5 cm

16

1

80

1920

Sham

Karamustafalioglu et al., 2010 53

HF HF Sham 35 Add-on . . Yes/nd . 30

20

80

24000

20

110

24000

.

Kauffmann et.al., 2004 54 LF Sham 12 Add-on . . Yes/2 5 cm 10

1

110

1200

Angled

Kazemi et al., 2016 55 LF Bi 30 Add-on 56 35.4 No 5 cm 20

1

120

50000

1/10

120/100

30000/ 75000

.

Klein et al., 199956

LF

Sham

67

Add-on

75

60

Yes/2

6 cm

10

1

110

1200

Angled

Koerselman et al., 2004 57 HF Sham 52 Add-on . 48.3 . 5 cm

10

20

80

8000

Angled

Kreuzer et al., 201558

HF

Sham

30

Add-on

59

45.1

No

6 cm

15

10

110

30000

Sham

Krstic et al., 2014 59 LF Sham 19 Add-on 100 48.8 Yes/2 5 cm 10

1

110

3000

Angled

Leuchter et al., 201560 sTMS Sham 202 Mono 60 45.9 No IAF+ 30 IAF + Sham

Levkovitz et al., 2015 61

dTMS

Sham

212

Mono

52

46.4

Yes/1

6 cm

25

18

120

49500

Sham

Li et al., 201462

TBS

Sham

60

Add-on

66

47.1

Yes/2

NN

10

#

80*

#

Angled

Lingeswaran et al., 2011 63 HF Sham 29 Add-on 61 35.9 No 5 cm

12

10

100

6000

Angled

Loo et al., 1999 64 HF Sham 18 . . 48.3 Yes/nd 5 cm 10

10

110

15000

Angled

Loo et al., 2003 65 Bi Sham 19 Add-on 63 51.2 Yes/1 5 cm 15

15/15

90/90

27000/27000

Others

Loo et al., 200766

HF

Sham

38

Add-on

47

47

Yes/2

5 cm

20

10

110

30000

Others

Martinot et al., 201067

HF

Sham

33

Add-on

64

47.1

Yes/2

5 cm

10

10

90

16000

Sham

McDonald et al., 2006 68

Bi

Sham

62

Add-on

51

51

Yes/3

5 cm

10

1/10

110

6000 / 10000

Angled

Mogg et al., 200869

HF

Sham

59

Add-on

62

53.5

Yes/nd

5 cm

10

10

110

10000

Sham

Mosimann et al. 2004 70 HF Sham 24 Add-on 42 61.6 Yes/2 5 cm 10

20

100

16000

Angled

Nahas et al., 200371

HF

Sham

23

Add-on

61

43

No

5 cm

10

5

110

16000

Angled

O’Reardon et al., 2007 72

HF

Sham

301

Mono

53

48.3

Yes/1

5 cm

20

10

120

60000

Sham

Padberg et al., 2002 73

HF

Sham

20

Add-on

65

55

Yes/2

5 cm

10

10

100

15000

Angled

Pallanti et al., 201074

LF

Bi

Sham

60

Add-on

58

48

Yes/2

5 cm

15

1

110

6300

1/10

110/100

6300/15000

Sham



Plewia et al., 2014 75

TBS

Sham

32

Add-on

62.5

47.5

No

EEG

30

$

80

$

Angled

Prasser et al., 2014 76

Bi

Sham

34

Add-on

50

46.5

Yes/nd

6 cm

15

1/10

110

15000

Sham

Rossini et al., 2005 77

HF

Sham

35

Add-on

65

57

Yes/2

5 cm

10

15

100

6000

Angled


HF

Sham

99

Aug

79

47.4

No

5 cm

10

15

100

9000

Angled


HF

LF

74

Add-on

71

53.5

Yes/1

5 cm

10

15

100

6000

1

100

9000

.

Rumi et al., 2005 80

HF

Sham

48

Aug

81

39

Yes/2

5 cm

20

5

120

25000

Sham

Speer et al., 2014 81 LF HF Sham 24 Mono 54 41.8 Yes/2 5 cm 15

1

110

24000

20

110

24000

Angled

Stern et al., 200782

HF

LF

Sham

35

Mono

73

53

Yes/1

5 cm

10

10

110

16000

1

110

16000

Angled

Su et al., 200583

HF

Sham

30

Add-on

73

43

Yes/2

5 cm

10

5/20

100

16000

Angled

Szuba et al., 2001 84 HF Sham 14 Mono 57 37.4 No . 10

10

100

10000

Angled

Triggs et al., 2010 85

HF

Sham

32

Add-on

62

45

Yes/2

5 cm

10

5

100

20000

Sham

Zhang et al., 2011 86

HF

Sham

28

Add-on

28

46

Yes/2

.

20

10

110

30000

Angled

Zheng et al., 2010 87

HF

Sham

34

Add-on

36

27.2

Yes/2

5 cm

20

15

110

60000

Angled

Zheng et al., 2015 88 HF Sham 32 Add-on 34 26.9 Yes/2 5 cm 20

15

110

60000

Angled

DLPFC: dorsolateral prefrontal córtex; MT: motor threshold; LF: low frequency; HF: high frequency; Bi: bilateral; TRD: treatment resistant depression; nd: not defined; Mono: monotherapy; Aug: augmentation; aTMS: accelerated

HF-transcranial magnetic stimulation; NN neuronavigation; TBS: theta burst stimulation; pTMS priming transcranial magnetic stimulation; EEG: electroencephalography; MRI: magnetic resonance imaging; @ Right-sided cTBS:

3600 stimuli delivered in 4 consecutive trains of 900 stimuli. * active motor threshold (aMT). !!! 1620 pulses per session in 54 triplet bursts with train duration of 2 seconds and an intertrain interval of 8 seconds. % LF protocol

primed with 20 trains of 5 s duration at 6 Hz and 90% of the RMT. + Please check the original study for more details regarding the IAF protocol. # Left-sided iTBS: 2s train every 10s for 570s (1800 pulses). Right-sided cTBS:

continuously for 120s (1800 pulses). $ Left-sided iTBS: 2 trains of 600 stimuli, 20 times for 2s, every 10s. Right-sided cTBS: continuously for 40s. For all studies, TBS consisted of 3-pulse 50Hz bursts every 200ms at 5



eTable 2. Relative odds ratios (OR) with 95% confidence intervals (CI) estimated from standard pairwise meta-analysis for every available direct comparison between the 9 interventions with respect to response. Heterogeneity standard deviation (𝜏𝜏) has been estimated using the methods of moments and is reported only for comparisons for which is estimable and larger than 0.

Comparison Study OR (95% CI) Comparison Study OR (95% CI) LF vs pTMS Fitzgerald (2008) 3.25 (0.89 - 11.9)

Bilateral vs HF

Blumberger (2012) 0.08 (0.01 - 0.67)

Bilateral vs pTMS Fitzgerald (2013) 0.93 (0.51 - 1.67) Fitzgerald (2012) 0.29 (0.01 - 7.56)

Sham vs TBS

Plewnia (2014) 3.86 (0.86 - 17.32) Blumberger (2016) 0.61 (0.19 - 1.90)

Li (2014) 5.20 (1.05 - 25.77) Hausmann (2004) 1.56 (0.34 - 7.11)

Chistyakov (2015) 1.25 (0.26 - 6.07) Summary 0.5 (0.15 - 1.6) Prasser (2014) 1.67 (0.34 - 8.26) 𝜏𝜏 = 0.58, 𝛪𝛪2 = 42% (0%, 80%) Summary 2.57 ( 1.17 - 5.62)

Bilateral vs Sham

Blumberger (2012) 0.18 (0.04 - 0.93) HF vs Sham

Anderson (2007) 0.08 (0.01 - 0.78) Fitzgerald (2012) 0.35 (0.01 - 9.08)

Avery (2006) 0.14 (0.03 - 0.7) Fitzgerald (2006) 0.11 (0.02 - 0.57)

Bakim (2012) 0.08 (0.01 - 0.56) Garcia-Toro (2006) 0.18 (0.01 - 3.59)

Blumberger (2012) 2.30 (0.19 - 27.30) McDonald (2006) 0.36 (0.04 - 3.16)

Fitzgerald (2003) 1.0 (0.02 - 52.85) Pallanti (2010) 0.44 (0.07 - 2.76)

Fitzgerald (2012) 1.2 (0.02 - 62.92) Prasser (2014) 0.31 (0.07 - 1.5)

George (2000) 0.06 (0.00 - 1.18) Fitzgerald (2016) 0.30 (0.03 - 3.16)

George (2010) 0.3 (0.1 - 0.87) Blumberger (2016) 0.18 (0.04 - 0.88) Hernandez-Ribas (2013) 0.16 (0.02 - 1.07) Hausmann (2004) 1.00 (0.22 - 4.47)

Herwig (2003) 0.08 (0.00 - 1.77) Loo (2003) 0.39 (0.3 - 5.21)

Herwig (2007) 1.01 (0.47 - 2.14) Summary 0.3 (0.17 - 0.52)

Loo (2007) 0.36 (0.08 - 1.72)

HF vs LF

Fitzgerald (2003) 3.15 (0.12 - 82.17)

Mogg (2008) 0.25 (0.06 - 1.03) Fitzgerald (2009) 1.07 (0.23 - 5.02)

Nahas (2003) 0.88 (0.16 - 4.87) Rossini (2010) 0.7 (0.27 - 1.81)

O' Reardon (2007) 0.49 (0.27 - 0.89) Stern (2007) 1.00 (0.18 - 5.47)

Padberg (2002) 0.10 (0.01 - 2.28) Isenberg (2005) 0.72 (0.15 - 3.54)

Rossini (a) (2005) 0.04 (0.00 - 0.37) DellOsso (2015) 0.69 (0.16 - 2.99)

Rossini (b) (2005) 0.73 (0.31 - 1.72) Eche (2012) 0.50 (0.06 - 4.47)

Rumi (2005) 0.04 (0.01 - 0.35) Speer (2014) 1.00 (0.02 - 56.46)

Stern (2007) 0.02 (0.00 - 0.48) Hu (2016) 1.13 (0.21 - 6.05)

Su (2005) 0.07 (0.01 - 0.70) GarcÌa-Anaya (2011) 1.00 (0.02 - 55.27)

Triggs (2010) 1.04 (0.22 - 4.91) Summary 0.83 (0.49 - 1.41) Zhang (2011) 0.42 (0.1 - 1.91) Bilateral vs

LF Fitzgerald (2011) 0.95 (0.49 - 1.83)

Zheng (2010) 0.04 (0.00 - 0.39) Pallanti (2010) 2.15 (0.52 - 9.00)



Kreuzer (2015) 1.00 (0.17 - 5.99) Kazemi (2016) 0.22 (0.04 - 1.11)

Berman (2000) 0.3 (0.01 - 8.33) Summary 0.84 (0.30 - 2.32) Boutros (2002) 1.43 (0.16 - 12.7) 𝜏𝜏 = 0.45, 𝛪𝛪2 = 54% (0%, 87%) Garcia-Toro-JNNP (2001) 0.66 (0.11 - 4.00) Sham vs

aTMS Baeken (2013) 2.25 (0.17 - 29.77)

Garcia-Toro-JAD (2006) 0.11 (0.01 - 1.00) Bilateral vs

TBS Prasser (2014) 0.52 (0.13 - 2.1)

Huang (2012) 0.65 (0.23 - 1.86) sTMS vs Sham Leuchter (2015) 0.92 (0.46 - 1.87)

Martinot (2010) 0.25 (0.05 - 1.17) dTMS vs Sham Levkovitz (2015) 0.67 (0.38 - 1.2)

Blumberger (2016) 0.29 (0.06 - 1.54) LF vs Sham

Aguirre (2011) 0.33 (0.06 - 1.97)

Hausmann (2004) 0.64 (0.14 - 2.94) Brunelin (2014) 1.15 (0.60 - 2.22)

Holtzheimer (2004) 0.88 (0.02 - 50.19) Fitzgerald (2003) 0.32 (0.01 - 8.26)

Mosimann (2004) 0.51 (0.02 - 13.84) Hoppner (2003) 2.33 (0.37 - 14.61)

Speer (2014) 1.00 (0.02 -56.46) Klein (1999) 0.34 (0.12 - 0.96)

Koerselman (2004) 1.00 (0.02 - 52.29) Pallanti (2010) 0.21 (0.04 - 1.16)

George (1997) 0.39 (0.01 - 11.76) Stern (2007) 0.02 (0.00 - 0.48)

Zheng (2015) 0.05 (0.01 - 0.46) Januel (2006) 0.04 (0.00 - 0.41)

Chen (2013) 0.1 (0.01 - 0.74) Kauffmann (2004) 0.5 (0.05 - 5.15)

Hu (2016) 0.8 (0.16 - 4.12) Krstic (2014) 0.1 (0.00 - 2.14) Karamustafalioglu (2010) 0.06 (0.01 - 0.34) Speer (2014) 1.00 (0.02 - 56.46)

Concerto (2015) 0.01 (0.0 - 0.26) Hu (2016) 0.71 (0.14 - 3.61)

Summary 0.31 (0.22 - 0.43) Summary 0.40 (0.2 - 0.82)

𝜏𝜏 = 0.37, 𝛪𝛪2 = 34% (4%, 55%) 𝜏𝜏 = 0.59, 𝛪𝛪2 = 46% (0%, 72%)



eTable 3. Relative odds ratios (OR) with 95% confidence intervals (CI) estimated from standard pairwise meta-analysis for every available direct comparison between the 9 interventions with respect to acceptability. Heterogeneity standard deviation (𝜏𝜏) has been estimated using the methods of moments and is reported only for comparisons for which is estimable and larger than 0.

Comparison Study OR (95%CI) Comparison Study OR (95%CI) LF vs pTMS Fitzgerald (2008) 0.19 (0.01 - 4.06)

Bilateral vs HF

Blumberger (2012) 3.67 (1.1 - 12.25)

Bilateral vs pTMS Fitzgerald (2013) 0.45 (0.16 - 1.25) Fitzgerald (2012) 0.11 (0.01 - 2.34)

HF vs Sham

Anderson (2007) 0.79 (0.1 - 6.50) Blumberger (2016) 0.52 (0.14 - 1.95)

Avery (2006) 1.07 (0.20 - 5.70) Hausmann (2004) 1.08 (0.1 - 11.79)

Bakim (2012) 0.92 (0.02 - 50.28) Summary 0.937 0.236 3.727 Blumberger (2012) 0.47 (0.14 - 1.55) 𝜏𝜏 = 1.08, 𝛪𝛪2 = 58% (0%, 86%) Fitzgerald (2003) 1.00 (0.02 - 52.85)

Bilateral vs Sham

Blumberger (2012) 1.71 (0.48 - 6.11)

Fitzgerald (2012) 9.80 (0.48 - 202.03) Fitzgerald (2012) 1.11 (0.22 - 5.61)

George (2000) 1.95 (0.04 - 105.52) Fitzgerald (2006) 7.93 (0.39 - 162.07)

George (2010) 0.70 (0.34 - 1.46) Garcia-Toro (2006) 1.95 (0.04 - 105.52) Hernandez-Ribas (2013) 0.91 (0.02 - 0.26) McDonald (2006) 4.04 (0.08 - 213.74)

Herwig (2003) 1.08 (0.02 - 58.66) Pallanti (2010) 1.00 (0.02 - 52.85)

Herwig (2007) 1.18 (0.47 - 2.96) Prasser (2014) 1.00 (0.1 - 10.57)

Loo (2007) 3.00 (0.29 - 31.63) Fitzgerald (2016) 1.00 (0.18 - 5.56)

Mogg (2008) 0.96 (0.18 - 5.21) Blumberger (2016) 0.66 (0.19 - 2.27)

Nahas (2003) 0.92 (0.02 - 50.28) Hausmann (2004) 0.31 (0.01 - 8.29)

O' Reardon (2007) 1.07 (0.46 - 2.46) Loo (2003) 5.59 (0.23 - 133.61)

Padberg (2002) 1.00 (0.02 - 55.27) Summary 1.22 (0.66 - 2.24) Rossini (a) (2005) 3.36 (0.13 - 88.39)

HF vs LF

Fitzgerald (2003) 1.00 (0.02 - 52.85)

Rossini (b) (2005) 1.02 (0.28 - 3.78) Fitzgerald (2009) 1.44 (0.03 - 77.68)

Rumi (2005) 0.92 (0.02 - 48.25) Rossini (2010) 0.77 (0.02 - 39.57)

Stern (2007) 2.17 (0.08 - 58.76) Stern (2007) 1.00 (0.02 - 55.27)

Su (2005) 1.95 (0.04 - 105.52) Isenberg (2005) 1.00 (0.02 - 53.89)

Triggs (2010) 1.28 (0.02 - 68.26) DellOsso (2015) 2.12 (0.2 - 22.9)

Zhang (2011) 1.00 (0.02 - 53.89) Eche (2012) 0.77 (0.01 - 43.93)

Zheng (2010) 1.26 (0.02 - 67.08) Speer (2014) 1.00 (0.02 - 56.46)

Kreuzer (2015) 8.68 (0.41 - 184.28) Hu (2016) 0.92 (0.05 - 16.49)

Berman (2000) 1.00 (0.02 - 55.27) GarcÌa-Anaya (2011) 1.00 (0.02 - 55.27)

Boutros (2002) 3.14 (0.24 - 41.51) Summary 1.15 (0.38 - 3.53) Garcia-Toro-JNNP (2001) 1.00 (0.02 - 54.83) Bilateral vs

LF Fitzgerald (2011) 2.61 (1.16 - 5.89)



Garcia-Toro-JAD (2006) 3.46 (0.82 - 14.59) Pallanti (2010) 1.00 (0.02 - 52.85)

Huang (2012) 1.00 (0.13 - 7.61) Kazemi (2016) 1.00 (0.02 - 53.66)

Martinot (2010) 0.43 (0.02 - 11.23) Summary 2.43 (1.11 - 5.3)

Blumberger (2016) 1.25 (0.31 - 5.04) Bilateral vs TBS Prasser (2014) 0.29 (0.01 - 7.44)

Hausmann (2004) 0.29 (0.01 - 7.70) sTMS vs Sham Leuchter (2015) 0.84 (0.48 - 1.47)

Holtzheimer (2004) 0.36 (0.03 - 5.11) dTMS vs Sham Levkovitz (2015) 1.53 (0.70 - 3.34)

Mosimann (2004) 1.63 (0.03 - 89.28) LF vs Sham

Aguirre (2011) 1.29 (0.08 - 22.42)

Speer (2014) 3.40 (0.12 - 96.70) Brunelin (2014) 1.22 (0.59 - 2.5)

Koerselman (2004) 2.08 (0.18 - 24.51) Fitzgerald (2003) 1.00 (0.02 - 52.85)

George (1997) 1.36 (0.02 - 79.96) Hoppner (2003) 1.00 (0.05 - 18.57)

Loo (1999) 1.00 (0.02 - 55.8) Klein (1999) 2.19 (0.19 - 25.3)

Zheng (2015) 1.28 (0.02 - 68.26) Pallanti (2010) 1.00 (0.02 - 52.85)

Chen (2013) 3.00 (0.11 - 82.4) Stern (2007) 2.17 (0.08 - 58.76)

Jakob (2008) 1.96 (0.04 - 104.76) Kauffmann (2004) 1.36 (0.02 - 79.96)

Szuba (2001) 1.73 (0.03 - 99.95) Krstic (2014) 1.35 (0.02 - 75.28)

Hansen (2004) 0.07 (0.00 - 1.67) Speer (2014) 3.40 (0.12 - 96.70)

Lingeswaran (2011) 0.64 (0.11 - 3.91) Hu (2016) 1.00 (0.06 - 17.90)

Bretlau (2008) 0.32 (0.03 - 3.30) Summary 1.30 (0.72 - 2.34) Hu (2016) 0.92 (0.05 - 16.49)

Sham vs TBS

Plewnia (2014) 1.71 (0.40 - 7.27)

Eschweiler (2000) 1.36 (0.02 - 79.96) Li (2014) 0.34 (0.01 - 17.91) Karamustafalioglu (2010) 1.88 (0.04 - 100.56) Chistyakov (2015) 0.29 (0.01 - 7.74)

Concerto (2015) 1.00 (0.02 - 53.66) Prasser (2014) 0.29 (0.01 - 7.44)

Summary 1.04 (0.78 - 1.40) Duprat (2016) 7.93 (0.39 - 162.07) Sham vs aTMS Baeken (2013) 1.00 (0.02 - 55.27) Summary 1.24 (0.42 - 3.71)



eTable 4. Relative odds ratios (OR) with 95% confidence intervals (CI) estimated from standard pairwise meta-analysis for every available direct comparison between the 9 interventions with respect to remission. Heterogeneity standard deviation (𝜏𝜏) has been estimated using the methods of moments and is reported only for comparisons for which is estimable and larger than 0.

Comparison Study OR (95%CI) Comparison Study OR (95%CI) Bilateral vs pTMS Fitzgerald (2013) 1.04 (0.57 - 1.89)

Bilateral vs Sham

Blumberger (2012) 0.1 (0.01 - 0.87)

Sham vs TBS Plewnia (2014) 3.37 (0.68 - 16.65) Fitzgerald (2012) 1.1 (0.02 - 57.88) sTMS vs Sham Leuchter (2015) 1.17 (0.46 - 3.02) Fitzgerald (2006) 0.03 (0.00 - 0.63)

HF vs Sham

Avery (2006) 0.13 (0.01 - 1.08) Garcia-Toro (2006) 1.95 (0.04 - 105.52)

Bakim (2012) 0.08 (0.01 - 0.81) Pallanti (2010) 0.47 (0.04 - 5.69)

Blumberger (2012) 1.1 (0.06 - 18.64) Blumberger (2016) 0.10 (0.01 - 0.84) Fitzgerald (2012) 1.2 (0.02 - 62.92) Summary 0.17 (0.06 - 0.52) George (2010) 0.33 (0.11 - 0.96)

HF vs LF

Fitzgerald (2009) 2.48 (0.43 - 4.34) Loo (2007) 0.56 (0.08 - 3.79) Stern (2007) 0.34 (0.04 - 2.87) Mogg (2008) 0.35 (0.08 - 1.51) Isenberg (2005) 0.61 (0.09 - 4.37) O' Reardon (2007) 0.40 (0.19 - 0.87) DellOsso (2015) 0.61 (0.08 - 4.98) Padberg (2002) 0.16 (0.01 - 3.85) Speer (2014) 1.00 (0.02 - 56.46) Rossini (a) (2005) 0.03 (0.00 - 0.55) Hu (2016) 0.90 (0.14 - 5.65) Rossini (b) (2005) 0.5 (0.22 - 1.11) Summary 0.86 (0.37 - 2.01) Rumi (2005) 0.12 (0.03 - 0.52)

Bilateral vs LF

Fitzgerald (2011) 0.83 (0.41 - 1.66) Stern (2007) 0.07 (0.00 - 1.52) Pallanti (2010) 3.86 (0.67 - 22.11) Su (2005) 0.05 (0.00 - 0.92) Kazemi (2016) 1.00 (0.23 - 4.31) Kreuzer (2015) 0.69 (0.13 - 3.79) Summary 1.11 (0.52 - 2.38) Boutros (2002) 1.38 (0.07 - 25.43) 𝜏𝜏 = 0.12, 𝛪𝛪2 = 22% (0%, 92%) Huang (2012) 0.53 (0.17 - 1.62) dTMSG Levkovitz (2015) 0.41 (0.21 - 0.8) Blumberger (2016) 0.31 (0.03 - 3.1)

LF vs Sham

Aguirre (2011) 1.29 (0.07 - 22.42) Holtzheimer (2004) 0.88 (0.02 - 50.19) Brunelin (2014) 1.46 (0.75 - 2.85) Mosimann (2004) 1.63 (0.03 - 89.28) Klein (1999) 0.27 (0.09 - 0.81) Speer (2014) 1.00 (0.02 - 56.46) Pallanti (2010) 0.12 (0.01 - 1.14) Koerselman (2004) 1.00 (0.02 - 52.29) Stern (2007) 0.20 (0.01 - 5.54) George (1997) 0.39 (0.01 - 11.76) Januel (2006) 0.04 (0.00 - 0.41) Hu (2016) 0.55 (0.07 - 4.01) Kauffmann (2004) 0.19 (0.01 - 2.66)

Summary 0.37 (0.26 - 0.52) Krstic (2014) 1.35 (0.02 - 75.28)

Bilateral vs HF

Blumberger (2012) 0.09 (0.01 - 0.79) Speer (2014) 1.00 (0.02 - 56.46) Fitzgerald (2012) 0.92 (0.02 - 48.25) Hu (2016) 0.61 (0.08 - 4.41) Blumberger (2016) 0.32 (0.08 - 1.33) Summary 0.40 (0.17 - 0.98) Summary 0.25 (0.08 - 0.77) 𝜏𝜏 = 0.80, 𝛪𝛪2 = 49% (0%, 75%)

Sham vs aTMS Baeken (2013) 1.00 (0.02 - 55.27)



eTable 5. Relative odds ratios estimated from the network meta-analysis comparing every pair of the 9 interventions with respect to remission (lower triangle) and acceptability (upper triangle). Values larger than 1 favor the intervention in the left for remission and the intervention in the right for acceptability. The interventions in the diagonal have been ordered according to their estimated relative ranking for remission. Values in parenthesis are the 95% confidence intervals and 𝜏𝜏 is the heterogeneity standard deviation for each outcome. Cells in gray correspond to statistically significant relative effects.

Drop-out rate, 𝝉𝝉 = 𝟎𝟎 Bilateral

TMS 2.33

(0.88,6.18) 0.54

(0.17,1.75) 0.68

(0.41,1.14) 0.62

(0.36,1.07) 0.98

(0.39,2.44) 0.64

(0.01,36.25) 0.53

(0.25,1.12) 0.64

(0.39,1.03) 0.96

(0.30,3.06) pTMS 0.23 (0.05,1.06)

0.29 (0.10,0.87)

0.27 (0.09,0.80)

0.42 (0.11,1.58)

0.27 (0.00,17.43)

0.23 (0.07,0.77)

0.27 (0.09,0.80)

1.25 (0.16,9.50)

1.30 (0.13,13.39) TBS 1.26

(0.41,3.86) 1.15

(0.36,3.75) 1.81

(0.48,6.86) 1.18

(0.02,75.27) 0.99

(0.29,3.34) 1.18

(0.40,3.49) 1.54

(0.71,3.34) 1.60

(0.40,6.43) 1.23

(0.18,8.47) HF-rTMS 0.92 (0.55,1.54)

1.43 (0.62,3.29)

0.94 (0.02,52.26)

0.78 (0.42,1.47)

0.94 (0.70,1.25)

1.56 (0.77,3.19)

1.62 (0.42,6.30)

1.25 (0.17,8.92)

1.01 (0.55,1.86) LF-rTMS 1.57

(0.63,3.90) 1.02

(0.02,58.09) 0.85

(0.41,1.78) 1.02

(0.64,1.64) 1.72

(0.42,7.10) 1.79

(0.29,11.11) 1.38

(0.15,12.74) 1.12

(0.31,3.97) 1.10

(0.29,4.15) dTMS 0.65 (0.01,38.89)

0.55 (0.21,1.43)

0.65 (0.30,1.42)

4.22 (0.06,281.72)

4.37 (0.06,341.58)

3.37 (0.04,315.48)

2.73 (0.04,174.24)

2.70 (0.04,175.09)

2.45 (0.03,180.62) aTMS 0.84

(0.01,48.01) 1.00

(0.02,55.27) 4.95

(1.03,23.71) 5.13

(0.73,35.96) 3.96

(0.39,40.41) 3.21

(0.76,13.47) 3.17

(0.72,13.99) 2.87

(0.47,17.65) 1.17

(0.02,91.18) sTMS 1.20 (0.68,2.10)

4.22 (1.96,9.05)

4.37 (1.10,17.47)

3.37 (0.52,22.05)

2.73 (1.78,4.20)

2.70 (1.51,4.82)

2.45 (0.74,8.07)

1.00 (0.02,62.31)

0.85 (0.22,3.35) Sham

Remission rate, 𝝉𝝉 = 𝟎𝟎. 𝟓𝟓𝟎𝟎



eTable 6. Results of the side-splitting approach for inconsistency for all outcomes. For each comparison the direct and indirect estimates (i.e. log-odds ratios) and the respective inconsistency factor (IF) are provided along with their standard errors (SE). P-values smaller than 0.10 correspond to statistically significant IFs (comparisons in red). (A = bilateral rTMS, B = dTMS, C = HF-rTMS, D = LF-rTMS, E = pTMS, F = sTMS, G = Sham, H = TBS, I = aTMS)

Response

Comp Direct SE(dir) Indirect SE(indir) IF SE(IF) P>|z|

G H .9395977 .4686947 .8848252 1.615658 .0547725 1.701493 0.974 A G -1.256336 .3340727 -1.616057 .4781769 .3597207 .5972458 0.547 A C -.6104508 .4959492 -.0869447 .3362143 -.5235061 .60703 0.388 A D -.1484396 .4197802 -.7746332 .3586632 .6261936 .5543196 0.259 A E -.0759863 .5695403 .7285276 .8695781 -.804514 1.039491 0.439

A H -.6384861 .8573344 -.351122 .5937489 -.2873641 1.040683 0.782

C G -1.139858 .1710237 -1.0105 .4707158 -.1293584 .4961956 0.794 C D -.1633636 .3312497 -.3455986 .3166015 .1822349 .4590632 0.691 D G -.8125145 .3046873 -.9341457 .3355812 .1216312 .4512795 0.788 D E 1.178641 .8198368 .3737766 .6391068 .8048639 1.039516 0.439

Acceptability

G H .2181317 .5573489 -1.537053 2.315499 1.755185 2.318464 0.449 A G .1788878 .3120456 .9232772 .4135238 -.7443894 .5226296 0.154 A C .1810542 .4019174 .5491726 .3601898 -.3681184 .547867 0.502 A D .8866398 .3982831 .0834757 .3864053 .8031641 .554922 0.148 A E -.8050688 .5243305 -1.215753 1.595889 .410684 1.679814 0.807 A H -1.002255 1.576048 .8418523 .632759 -1.844107 1.661252 0.267 C G .0352255 .1500544 .6513205 .6387914 -.616095 .6546312 0.347 C D .1394868 .5717886 .0743732 .2980942 .0651136 .6448404 0.920 D G .2680515 .2992831 -.5495423 .4023971 .8175937 .4994025 0.102 D E -1.677272 1.570938 -1.266438 .5950238 -.4108339 1.679848 0.807

Remission

A G -1.860978 .5780641 -1.038708 .5522552 -.8222701 .8420759 0.329 A C -1.479254 .6373556 .1919544 .4777284 -1.671208 .8103051 0.039 A D .1205507 .4049801 -1.595296 .5769581 1.715847 .6894084 0.013 A E .0368777 .5893562 -2.878346 128.9937 2.915224 128.995 0.982 C G -1.052843 .2273716 -.5487892 .7192258 -.504054 .750707 0.502 C D -.1866987 .4901338 .1147457 .4126753 -.3014444 .6413605 0.638 D G -.7393991 .3614578 -1.441906 .4843644 .7025068 .6079902 0.248



eTable 7. Relative odds ratios estimated from the sensitivity analysis without studies at high risk of overall bias comparing every pair of the 9 interventions with respect to response (lower triangle) and acceptability (upper triangle). Values larger than 1 favor the intervention in the left for response and the intervention in the right for acceptability. The interventions in the diagonal have been ordered according to their estimated relative ranking for response. Values in parenthesis are the 95% confidence intervals and 𝜏𝜏 is the heterogeneity standard deviation for each outcome. Cells in grey correspond to statistically significant relative effects.

Acceptability, 𝝉𝝉 = 𝟎𝟎

pTMS 0.30 (0.01,6.78)

0.20 (0.01,4.65)

0.16 (0.01,4.38)

0.19 (0.00,30.74)

0.19 (0.01,4.06)

0.29 (0.01,7.27)

0.16 (0.01,3.79)

0.19 (0.01,4.31)

2.12 (0.37,12.23)

Bilateral TMS

0.69 (0.41,1.16)

0.55 (0.17,1.77)

0.64 (0.01,36.66)

0.63 (0.36,1.10)

0.99 (0.39,2.48)

0.54 (0.25,1.13)

0.64 (0.39,1.05)

2.56 (0.46,14.32)

1.21 (0.68,2.14) HF-rTMS 0.79

(0.26,2.43) 0.93

(0.02,52.18) 0.91

(0.54,1.56) 1.43

(0.62,3.29) 0.78

(0.41,1.47) 0.93

(0.70,1.25) 3.23

(0.47,22.14) 1.52

(0.57,4.08) 1.26

(0.49,3.22) TBS 1.18 (0.02,75.32)

1.15 (0.35,3.77)

1.81 (0.48,6.87)

0.99 (0.29,3.34)

1.18 (0.40,3.49)

3.63 (0.14,95.06)

1.72 (0.10,29.02)

1.42 (0.09,23.20)

1.13 (0.06,20.75) aTMS 0.98

(0.02,55.68) 1.53

(0.03,91.24) 0.84

(0.01,48.01) 1.00

(0.02,55.27) 3.25

(0.62,16.90) 1.53

(0.84,2.79) 1.27

(0.78,2.07) 1.01

(0.37,2.72) 0.89

(0.05,14.96) LF-rTMS 1.57 (0.62,3.92)

0.85 (0.41,1.80)

1.02 (0.63,1.66)

5.48 (0.69,43.82)

2.59 (0.71,9.41)

2.14 (0.63,7.21)

1.70 (0.39,7.38)

1.51 (0.07,30.66)

1.69 (0.48,5.98) dTMS 0.55

(0.21,1.43) 0.65

(0.30,1.42) 7.54

(0.91,62.68) 3.56

(0.92,13.77) 2.94

(0.82,10.60) 2.34

(0.51,10.72) 2.08

(0.10,43.35) 2.32

(0.61,8.77) 1.38

(0.25,7.56) sTMS 1.20 (0.68,2.10)

8.18 (1.47,45.57)

3.86 (2.24,6.65)

3.19 (2.29,4.44)

2.53 (1.04,6.16)

2.25 (0.14,36.11)

2.52 (1.55,4.08)

1.49 (0.46,4.81)

1.08 (0.31,3.74)

Sham

Response, 𝝉𝝉 = 𝟎𝟎. 𝟓𝟓𝟐𝟐



eTable 8. Relative odds ratios estimated from the sensitivity analysis using only studies on primary use of rTMS (i.e. on treatment resistant patients and as an add-on intervention) comparing every pair of the 9 interventions with respect to response (lower triangle) and acceptability (upper triangle). Values larger than 1 favor the intervention in the left for response and the intervention in the right for acceptability. The interventions in the diagonal have been ordered according to their estimated relative ranking

for response. Values in parenthesis are the 95% confidence intervals and 𝜏𝜏 is the heterogeneity standard deviation for each outcome. Cells in grey correspond to statistically significant relative effects.


pTMS 0.43 (0.16,1.14)

0.29 (0.10,0.87)

0.23 (0.05,1.06)

0.27 (0.00,17.43)

0.27 (0.09,0.80)

0.42 (0.11,1.58)

0.23 (0.07,0.77)

0.27 (0.09,0.80)

1.09 (0.64,1.88)

Bilateral rTMS

0.68 (0.41,1.14)

0.54 (0.17,1.75)

0.64 (0.01,36.25)

0.62 (0.36,1.07)

0.98 (0.39,2.44)

0.53 (0.25,1.12)

0.64 (0.39,1.03)

1.20 (0.59,2.43)

1.09 (0.66,1.80) HF-rTMS 0.79

(0.26,2.43) 0.94

(0.02,52.26) 0.92

(0.55,1.54) 1.43

(0.62,3.29) 0.78

(0.42,1.47) 0.94

(0.70,1.25) 1.82

(0.57,5.79) 1.67

(0.59,4.68) 1.52

(0.53,4.38) TBS 1.18 (0.02,75.27)

1.15 (0.36,3.75)

1.81 (0.48,6.86)

0.99 (0.29,3.34)

1.18 (0.40,3.49)

2.53 (0.17,36.67)

2.31 (0.17,31.92)

2.12 (0.16,28.75)

1.39 (0.09,22.19) aTMS 0.98

(0.02,55.58) 1.53

(0.03,91.24) 0.84

(0.01,48.01) 1.00

(0.02,55.27) 1.46

(0.76,2.80) 1.33

(0.85,2.08) 1.22

(0.77,1.91) 0.80

(0.28,2.31) 0.57

(0.04,7.91) LF-rTMS 1.57 (0.63,3.90)

0.85 (0.41,1.78)

1.02 (0.64,1.64)

- - - - - - dTMS 0.55 (0.21,1.43)

0.65 (0.30,1.42)

- - - - - - - sTMS 1.20 (0.68,2.10)

5.70 (2.86,11.35)

5.21 (3.27,8.30)

4.76 (3.27,6.92)

3.12 (1.14,8.55)

2.25 (0.17,29.77)

3.91 (2.49,6.14) - - Sham

Response, 𝝉𝝉 = 𝟎𝟎



eTable 9. Relative odds ratios estimated from the sensitivity analysis using only studies with at least 15 sessions comparing every pair of the 9 interventions with respect to response (lower triangle) and acceptability (upper triangle). Values larger than 1 favor the intervention in the left for response and the intervention in the right for acceptability. The interventions in the diagonal have been ordered according to their estimated relative ranking for response. Values in parenthesis are the 95% confidence intervals and 𝜏𝜏 is the heterogeneity standard deviation for each outcome. Cells in grey correspond to statistically significant relative effects.


pTMS 0.45 (0.16,1.25)

0.30 (0.09,0.98)

0.20 (0.04,1.02)

0.31 (0.00,20.37)

0.28 (0.09,0.90)

0.48 (0.12,1.93)

0.26 (0.07,0.94)

0.31 (0.10,0.99)

0.93 (0.25,3.40)

Bilateral rTMS

0.68 (0.38,1.20)

0.44 (0.12,1.59)

0.70 (0.01,40.06)

0.62 (0.35,1.10)

1.07 (0.42,2.74)

0.59 (0.27,1.26)

0.70 (0.42,1.18)

1.20 (0.27,5.26)

1.29 (0.64,2.62) HF-rTMS 0.64

(0.18,2.24) 1.03

(0.02,57.96) 0.92

(0.51,1.64) 1.58

(0.67,3.72) 0.86

(0.44,1.68) 1.03

(0.72,1.47) 1.53

(0.24,9.68) 1.65

(0.44,6.11) 1.28

(0.34,4.75) TBS 1.61 (0.02,105.75)

1.42 (0.39,5.22)

2.46 (0.59,10.28)

1.34 (0.36,5.05)

1.61 (0.48,5.33)

1.79 (0.07,43.39)

1.93 (0.10,35.48)

1.50 (0.08,26.35)

1.17 (0.05,25.88) aTMS 0.89

(0.02,50.65) 1.53

(0.03,91.24) 0.84

(0.01,48.01) 1.00

(0.02,55.27) 1.53

(0.35,6.72) 1.65

(0.82,3.34) 1.28

(0.69,2.37) 1.00

(0.26,3.88) 0.86

(0.05,15.51) LF-rTMS 1.73 (0.68,4.41)

0.94 (0.44,2.03)

1.13 (0.67,1.89)

2.70 (0.38,19.12)

2.91 (0.67,12.58)

2.26 (0.57,8.94)

1.77 (0.29,10.71)

1.51 (0.07,33.93)

1.76 (0.42,7.40) dTMS 0.55

(0.21,1.43) 0.65

(0.30,1.42) 3.71

(0.50,27.42) 4.00

(0.88,18.29) 3.10

(0.74,13.04) 2.43

(0.38,15.41) 2.08

(0.09,47.93) 2.42

(0.55,10.76) 1.38

(0.21,8.99) sTMS 1.20 (0.68,2.10)

4.02 (0.93,17.47)

4.34 (2.20,8.58)

3.37 (2.11,5.36)

2.64 (0.75,9.22)

2.25 (0.13,38.16)

2.63 (1.42,4.86)

1.49 (0.41,5.45)

1.08 (0.28,4.22) Sham

Response, 𝝉𝝉 = 𝟎𝟎. 𝟓𝟓𝟗𝟗

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62. Li CT, Chen MH, Juan CH, et al. Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study. Brain. 2014;137(Pt 7):2088-2098.

63. Lingeswaran A. Repetitive Transcranial Magnetic Stimulation in the Treatment of depression: A Randomized, Double-blind, Placebo-controlled Trial. Indian J Psychol Med. 2011;33(1):35-44.

64. Loo C, Mitchell P, Sachdev P, McDarmont B, Parker G, Gandevia S. Double-blind controlled investigation of transcranial magnetic stimulation for the treatment of resistant major depression. Am J Psychiatry. 1999;156(6):946-948.

65. Loo CK, Mitchell PB, Croker VM, et al. Double-blind controlled investigation of bilateral prefrontal transcranial magnetic stimulation for the treatment of resistant major depression. Psychol Med. 2003;33(1):33-40.

66. Loo CK, Mitchell PB, McFarquhar TF, Malhi GS, Sachdev PS. A sham-controlled trial of the efficacy and safety of twice-daily rTMS in major depression. Psychol Med. 2007;37(3):341-349.

67. Paillere Martinot ML, Galinowski A, Ringuenet D, et al. Influence of prefrontal target region on the efficacy of repetitive transcranial magnetic stimulation in patients with



medication-resistant depression: a [(18)F]-fluorodeoxyglucose PET and MRI study. Int J Neuropsychopharmacol. 2010;13(1):45-59.

68. McDonald WM, Easley K, Byrd EH, et al. Combination rapid transcranial magnetic stimulation in treatment refractory depression. Neuropsychiatric Disease and Treatment. 2006;2(1):85-94.

69. Mogg A, Pluck G, Eranti SV, et al. A randomized controlled trial with 4-month follow- up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression. Psychol Med. 2008;38(3):323-333.

70. Mosimann UP, Schmitt W, Greenberg BD, et al. Repetitive transcranial magnetic stimulation: a putative add-on treatment for major depression in elderly patients. Psychiatry research. 2004;126(2):123-133.

71. Nahas Z, Kozel FA, Li X, Anderson B, George MS. Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy. Bipolar disorders. 2003;5(1):40-47.

72. O'Reardon JP, Cristancho P, Pilania P, Bapatla KB, Chuai S, Peshek AD. Patients with a major depressive episode responding to treatment with repetitive transcranial magnetic stimulation (rTMS) are resistant to the effects of rapid tryptophan depletion. Depress Anxiety. 2007;24(8):537-544.

73. Padberg F, Zwanzger P, Keck ME, et al. Repetitive transcranial magnetic stimulation (rTMS) in major depression: Relation between efficacy and stimulation intensity. Neuropsychopharmacology. 2002;27(4):638-645.

74. Pallanti S, Bernardi S, Di Rollo A, Antonini S, Quercioli L. Unilateral low frequency versus sequential bilateral repetitive transcranial magnetic stimulation: Is simpler better for treatment of resistant depression? Neuroscience. 2010;167(2):323-328.

75. Plewnia C, Pasqualetti P, Grosse S, et al. Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. J Affect Disord. 2014;156:219-223.

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s e t

im st e s

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a

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wor

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anal

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imat

es

eFigure 1

(A) (B)

Direct comparisons in the network Direct comparisons in the network

AvsC AvsD AvsE AvsG AvsH BvsG CvsD CvsG DvsE DvsG FvsG GvsH GvsI AvsC AvsD AvsE AvsG AvsH BvsG CvsD CvsG DvsE DvsG FvsG GvsH GvsI

Mixed estimates Mixed estimates AvsC 8.8 8.2 4.2 26.0 3.4 12.3 29.5 4.2 0.1 3.4 AvsC 7.1 12.3 0.7 27.6 0.9 4.8 36.7 0.7 8.2 0.9 AvsD 6.1 12.7 6.5 21.2 2.8 17.5 11.4 6.5 12.6 2.8 AvsD 5.2 30.2 1.7 25.9 0.8 6.8 1.6 1.7 25.1 0.8 AvsE 1.6 3.4 65.4 5.7 0.7 4.7 3.0 11.4 3.4 0.7 AvsE 0.7 4.1 78.4 3.5 0.1 0.9 0.2 8.5 3.4 0.1 AvsG 7.9 8.6 4.4 37.7 4.9 6.2 14.1 4.4 6.8 4.9 AvsG 7.7 17.2 1.0 41.4 1.3 3.3 11.0 1.0 14.8 1.3 AvsH 4.5 5.0 2.5 21.7 14.5 3.6 8.1 2.5 3.9 33.7 AvsH 4.4 9.9 0.6 23.9 5.2 1.9 6.3 0.6 8.5 38.7 BvsG 100.0 BvsG 100.0 CvsD 3.2 6.2 3.2 5.4 0.7 38.3 22.6 3.2 16.4 0.7 CvsD 3.3 11.1 0.6 8.2 0.3 10.4 36.9 0.6 28.4 0.3 CvsG 4.0 2.1 1.1 6.3 0.8 11.5 64.0 1.1 8.4 0.8 CvsG 3.2 0.3 3.4 0.1 4.6 83.9 4.3 0.1 DvsE 4.1 8.7 29.2 14.5 1.9 11.9 7.8 11.4 8.6 1.9 DvsE 3.1 18.0 37.1 15.5 0.5 4.1 1.0 5.3 15.0 0.5 DvsG 7.1 3.7 9.5 1.2 26.2 26.3 3.7 21.0 1.2 DvsG 2.1 15.5 0.9 13.8 0.4 10.7 12.9 0.9 42.3 0.4 FvsG 100.0 FvsG 100.0 GvsH 2.2 2.4 1.3 10.7 16.6 1.8 4.0 1.3 1.9 57.7 GvsH 1.0 2.2 0.1 5.3 8.6 0.4 1.4 0.1 1.9 78.8 GvsI 99.8 GvsI 0.1 0.1 99.6

Indirect estimates Indirect estimates AvsB 4.8 5.3 2.7 23.1 3.0 38.8 3.8 8.6 2.7 4.2 3.0 AvsB 4.6 10.2 0.6 24.6 0.8 40.7 2.0 6.5 0.6 8.8 0.8 AvsF 4.8 5.3 2.7 23.1 3.0 3.8 8.6 2.7 4.2 38.8 3.0 AvsF 4.6 10.2 0.6 24.6 0.8 2.0 6.5 0.6 8.8 40.7 0.8 AvsI 4.8 5.3 2.7 23.1 3.0 3.8 8.6 2.7 4.2 3.0 38.8 AvsI 4.6 10.2 0.6 24.6 0.8 2.0 6.5 0.6 8.8 0.8 40.6 BvsC 2.2 1.2 0.6 3.5 0.5 44.3 6.4 35.6 0.6 4.7 0.5 BvsC 1.6 0.2 1.8 0.1 47.8 2.4 43.8 2.2 0.1 BvsD 4.5 2.3 6.0 0.8 36.7 16.6 16.6 2.3 13.3 0.8 BvsD 1.3 9.1 0.5 8.1 0.3 41.0 6.3 7.6 0.5 25.0 0.3 BvsE 3.0 2.7 22.9 15.2 2.0 29.2 4.6 7.6 6.4 4.4 2.0 BvsE 3.1 6.0 26.2 16.7 0.5 29.6 1.7 4.8 3.3 7.6 0.5 BvsF 50.0 50.0 BvsF 50.0 50.0 BvsH 1.3 1.4 0.7 6.1 9.5 42.7 1.0 2.3 0.7 1.1 33.1 BvsH 0.5 1.2 0.1 2.8 4.6 46.7 0.2 0.8 0.1 1.0 42.0 BvsI 50.0 49.9 BvsI 50.0 49.9 CvsE 5.6 4.3 28.3 16.2 2.1 11.2 20.0 8.5 1.7 2.1 CvsE 4.6 6.9 29.8 17.7 0.6 3.7 25.3 3.8 7.0 0.6 CvsF 2.2 1.2 0.6 3.5 0.5 6.4 35.6 0.6 4.7 44.3 0.5 CvsF 1.6 0.2 1.8 0.1 2.4 43.8 2.2 47.8 0.1 CvsH 3.5 2.6 1.3 2.9 10.3 7.5 33.2 1.3 3.5 33.8 CvsH 2.2 1.4 0.1 1.1 4.8 2.7 43.2 0.1 1.2 43.2 CvsI 2.2 1.2 0.6 3.5 0.5 6.4 35.7 0.6 4.7 0.4 44.3 CvsI 1.7 0.2 1.7 0.1 2.4 43.8 2.2 47.8 DvsF 4.5 2.3 6.0 0.8 16.6 16.6 2.3 13.3 36.7 0.8 DvsF 1.3 9.1 0.5 8.1 0.3 6.3 7.6 0.5 25.0 41.0 0.3 DvsH 1.2 6.2 3.2 0.8 9.7 16.9 15.8 3.2 13.3 29.9 DvsH 0.8 10.6 0.6 5.9 4.5 6.4 7.2 0.6 25.1 38.2 DvsI 4.5 2.3 6.0 0.8 16.6 16.6 2.3 13.3 0.8 36.7 DvsI 1.3 9.2 0.5 8.1 0.3 6.3 7.6 0.5 25.0 0.2 40.9 EvsF 3.0 2.7 22.9 15.2 2.0 4.6 7.6 6.4 4.4 29.2 2.0 EvsF 3.1 6.0 26.2 16.7 0.5 1.7 4.8 3.3 7.6 29.6 0.5 EvsG 4.2 3.8 32.3 21.5 2.8 6.6 10.8 9.0 6.2 2.8 EvsG 4.4 8.5 37.3 23.6 0.8 2.5 6.8 4.7 10.7 0.8 EvsH 2.4 2.0 26.8 12.6 9.8 4.5 7.0 6.8 4.2 23.8 EvsH 2.9 5.5 27.7 15.7 3.6 1.7 4.6 3.4 7.3 27.5 EvsI 3.0 2.7 22.9 15.2 2.0 4.6 7.6 6.4 4.4 2.0 29.2 EvsI 3.1 6.0 26.3 16.7 0.5 1.7 4.8 3.3 7.6 0.5 29.5 FvsH 1.3 1.4 0.7 6.1 9.5 1.0 2.3 0.7 1.1 42.7 33.1 FvsH 0.5 1.2 0.1 2.8 4.6 0.2 0.8 0.1 1.0 46.7 42.0 FvsI 50.0 49.9 FvsI 50.0 49.9 HvsI 1.3 1.4 0.7 6.1 9.6 1.0 2.3 0.7 1.1 33.1 42.6 HvsI 0.5 1.2 0.1 2.8 4.6 0.2 0.7 0.1 1.0 42.1 46.6

Entire network 2.7 3.7 9.3 11.1 3.7 10.1 7.8 13.4 3.6 5.6 10.1 8.8 10.1 Entire network 2.5 6.7 9.6 12.0 1.4 10.5 2.9 12.4 1.4 9.7 10.5 9.7 10.5

Included studies 4 3 1 11 1 1 10 43 1 12 1 4 1 Included studies 4 3 1 11 1 1 10 50 1 11 1 5 1



eFigure 2

(A) (B)

LF-rTMS

HF-rTMS

Direct comparisons in the network

dTMS

pTMS

bilateral rTMS

sTMS

aTMS

Sham TBS

AvsC AvsD AvsE AvsG BvsG CvsD CvsG DvsG FvsG GvsH GvsI

Mixed estim

GvsI Indirect estimates

0.1 99.6

Net

wor

k m

eta-

anal

ysis

est

imat

es

ates AvsC 17.1 21.4 15.9 13.1 24.2 8.3 AvsD 12.9 45.6 13.8 13.9 1.0 12.8 AvsE 100.0 AvsG 14.9 21.3 18.4 9.2 24.1 12.1 BvsG 100.0 CvsD 8.1 14.3 6.1 25.9 25.8 19.7 CvsG 3.8 0.3 4.0 6.5 79.3 6.2 DvsG 5.5 14.2 8.7 21.3 26.8 23.5 FvsG 100.0 GvsH 99.9

AvsB 9.6 13.8 11.9 35.3 6.0 15.6 7.8 AvsF 9.6 13.8 11.9 6.0 15.6 7.8 35.3 AvsH 9.6 13.8 11.9 6.0 15.6 7.8 35.3 AvsI 9.6 13.8 11.9 6.0 15.6 7.8 35.3 BvsC 2.0 0.1 2.1 47.2 3.4 41.9 3.3 BvsD 3.5 9.0 5.5 37.1 13.4 16.9 14.8 BvsE 7.1 10.2 26.1 8.8 26.1 4.4 11.5 5.8 BvsF 50.0 50.0 BvsH 50.0 50.0 BvsI 50.0 49.9 CvsE 11.1 13.8 35.2 10.3 8.5 15.7 5.3 CvsF 2.0 0.1 2.1 3.4 41.9 3.3 47.2 CvsH 2.0 0.1 2.1 3.4 41.9 3.3 47.2 CvsI 2.0 0.1 2.1 3.4 41.9 3.3 47.2 DvsE 7.5 26.5 42.0 8.0 8.1 0.6 7.4 DvsF 3.5 9.0 5.5 13.4 16.9 14.8 37.1 DvsH 3.5 9.0 5.5 13.4 16.9 14.8 37.1 DvsI 3.5 9.0 5.5 13.4 16.9 14.8 37.0 EvsF 7.1 10.2 26.1 8.8 4.4 11.5 5.8 26.1 EvsG 9.6 13.8 35.3 11.9 6.0 15.6 7.8 EvsH 7.1 10.2 26.1 8.8 4.4 11.5 5.8 26.1 EvsI 7.1 10.2 26.1 8.8 4.4 11.5 5.8 26.1 FvsH 50.0 50.0 FvsI 50.0 49.9 HvsI 50.0 49.9

Entire network 5.6 9.2 9.9 6.7 9.9 6.4 15.5 6.9 9.9 9.9 9.9

Included studies 3 3 1 6 1 6 24 10 1 1 1



0 50 100

Percent

0 50 100

0 50 100

0 50 100

C - A

D - A

D - C

E - A

E - D

G - A

G - B

G - C

G - D

G - F

H - A

H - G

I - G

C - A

D - A

D - C

E - A

E - D

G - A

G - B

G - C

G - D

G - F

H - A

H - G

I - G

C - A

D - A

D - C

E - A

E - D

G - A

G - B

G - C

G - D

G - F

H - A

H - G

I - G

20 30 40 50 60

.2 .4 .6 .8 1 10 15 20 25 30

eFigure 3

C - A

D

- A

D - C

E - A

E - D

G - A

G

- B

G - C

G - D

G

- F H

- A

H - G

I - G

Baseline severity



Deep rTMS

1 2 3 4 5 6 7 8 9 Priming low-frequency rTMS

1 2 3 4 5 6 7 8 9

Deep rTMS

1 2 3 4 5 6 7 8 9 Priming low-frequency rTMS

1 2 3 4 5 6 7 8 9

eFigure 4

(A) (B)

Accelarated rTMS Bilateral rTMS Accelarated rTMS Bilateral rTMS

1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9

High-frequency rTMS Low-frequency rTMS

High-frequency rTMS Low-frequency rTMS

1 2 3 4 5 6

7

8

9 1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9

Sham Synchronized TMS Theta-burst stimulation Sham Synchronized TMS Theta-burst stimulation

1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9

Rank 1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9

Rank

abili

ties

.4 .

6 .8

1

0 .2

.4

.6 .

8 1

0

.2 .

4 .6

.8

1

0 .2

.4

.6 .

8 1

0

.2 .

4 .6

.8

1

0 .2

.4

.6 .

8 1

0 .2

.4

.6 .

8 1

0

.2 .

4 .6

.8

1

0 .2

.4

.6 .

8 1

Pro

babi

litie

s 0

.2 .

4 .6

.8

1

0 .2

.4

.6 .

8 1

0

.2 .

4 .6

.8

1

0 .2

.4

.6 .

8 1

0

.2 .

4 .6

.8

1

0 .2

.4

.6 .

8 1

0 .2

.4

.6 .

8 1

0

.2 .

4 .6

.8

1

0 .2

.4

.6 .

8 1



eFigure 5

pTMS

bilateral rTMS

dTMS

aTMS HF-rTMS

Sham LF-rTMS TBS

sTMS

0 20 40 60 80 100 SUCRA percentages for response

SU

CR

A p

erce

ntag

es fo

r acc

epta

bilit

y 0

20

40

60

80

100



79.0%

52.7%

55.3%

75.4%

.2 .

4 .6

.8

0

eFigure 6

(A) (B)

Accelarated rTMS Bilateral rTMS Deep rTMS

Accelarated rTMS Bilateral rTMS Deep rTMS

1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9

High-frequency rTMS Low-frequency rTMS Priming low-frequency rTMS High-frequency rTMS Low-frequency rTMS Priming low-frequency rTMS

1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9

Sham Synchronized TMS Theta-burst stimulation

1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9

Sham Synchronized TMS Theta-burst stimulation

16.1% 16.6%

1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9

Rank 1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9

Rank

56.6%

34.8%

63.5%

.2 .

4 .6

.8

.2 .

4 .6

.8

.2 .

4 .6

.8

0 1

0 1

0 1

.2 .

4 .6

.8

.2 .

4 .6

.8

.2 .

4 .6

.8

0 1

0 1

0 1

.2 .

4 .6

.8

.2 .

4 .6

.8

.2 .

4 .6

.8

0 1

0 1

0 1

.2 .

4 .6

.8

.2 .

4 .6

.8

.2 .

4 .6

.8

0 1

0 1

0 1

.2 .

4 .6

.8

.2 .

4 .6

.8

1 0

1 0

1

.2 .

4 .6

.8

.2 .

4 .6

.8

.2 .

4 .6

.8

0 1

0 1

0 1



eFigure 7

Loop IF

95% CI

(A)

(B)

(C)

0 1 2 3 4 5

A-D-E A-C-D A-C-G A-D-G A-G-H C-D-G

1.10 0.64 0.61 0.36 0.35 0.21

(0.00,2.65) (0.00,1.80) (0.00,1.65) (0.00,1.33) (0.00,2.06) (0.00,0.97)

A-G-H

A-D-G

A-C-D

C-D-G

A-C-G

A-D-E

1.68

0.95

0.56

0.37

0.07

0.01

(0.00,5.18)

(0.00,2.11)

(0.00,2.14)

(0.00,1.67)

(0.00,1.13)

(0.00,3.35)

A-C-D

A-D-G

A-C-G

C-D-G

1.74

1.25

0.79

0.14

(0.19,3.30)

(0.00,2.63)

(0.00,2.41)

(0.00,1.21)



Sham more effective than comparison

average

rTMS more effective than comparison average

rTMS more acceptable than comparison average

Sham more acceptable than comparison

average

eFigure 8

(A)

-4 -2 0 2 4

(B)

-4 -2 0 2 4

(C)

-4 -2 0 2 4 ln(OR) centered at comparison-specific pooled ln(OR)

A vs G B vs G C vs G D vs G F vs G H vs G I vs G

Sham more effective than comparison

average

rTMS more effective than comparison average

Stan

dard

err

or o

f ln(

OR

) St

anda

rd e

rror

of l

n(O

R)

Stan

dard

err

or o

f ln(

OR

) 2

1.5

1 .5

0

2 1.

5 1

.5

0 2

1.5

1 .5

0



eFigure 9 (A)

AvsC AvsD AvsE AvsG AvsH BvsG CvsD CvsG DvsE DvsG FvsG GvsH GvsI AvsB AvsF AvsI

BvsC BvsD BvsE BvsF BvsH BvsI

CvsE CvsF CvsH CvsI

DvsF DvsH DvsI EvsF EvsG EvsH EvsI

FvsH FvsI HvsI

Entire network

0 20 40 60 80 100 Percentage contribution of direct comparisons

(B)

AvsC AvsD AvsE AvsG AvsH BvsG CvsD CvsG DvsE DvsG FvsG GvsH GvsI AvsB AvsF AvsI

BvsC BvsD BvsE BvsF BvsH BvsI

CvsE CvsF CvsH CvsI

DvsF DvsH DvsI EvsF EvsG EvsH EvsI

FvsH FvsI HvsI

Entire network

0 20 40 60 80 100 Percentage contribution of direct comparisons

AvsC AvsD AvsE AvsG AvsH BvsG CvsD CvsG DvsE DvsG FvsG GvsH GvsI

AvsC

CvsG

AvsD

DvsE

AvsE

DvsG

AvsG

FvsG

AvsH

GvsH

BvsG

GvsI

CvsD



Documents

Supplementary Online ContentSupplementary Online Content . Brunoni AR, Chaimani A, Moffa AH, et al. Repetitive transcranial magnetic stimulation for the acute treatment of major depressive