Introduction: The clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) in Japan has not been adequately investigated. Furthermore, the relationship between stimulation-site pain and the antidepressant effects of rTMS has not been thoroughly examined. Therefore, this study aimed to clarify (1) the real-world efficacy and safety of rTMS for TRD in Japan and (2) the relationship between stimulation-site pain and clinical improvement of depressive symptoms. Methods: We conducted a retrospective observational study involving 50 right-handed patients with TRD. All patients received high-frequency rTMS for up to 6 weeks. Depressive symptoms were assessed using the Montgomery-Åsberg depression rating scale (MADRS). Pain at the stimulation site was reported by the patients using a visual analog scale (VAS) after each session. Remission and response rates at 3 and 6 weeks were calculated based on the MADRS scores. The correlation between changes in the MADRS and VAS scores was examined. Results: Remission and response rates were 36% and 46%, respectively, at the end of 3 weeks, and 60% and 70%, respectively, at 6 weeks. At the end of the treatment, there was significant correlation between the reduction of MADRS and VAS scores (r = 0.42, p = 0.003). Conclusion: This study demonstrates the clinical efficacy of rTMS in Japan and the correlation between its antidepressant effects and stimulation-site pain.

1.
Liu
Q
,
He
H
,
Yang
J
,
Feng
X
,
Zhao
F
,
Lyu
J
.
Changes in the global burden of depression from 1990 to 2017: findings from the global burden of disease study
.
J Psychiatr Res
.
2020
;
126
:
134
40
.
2.
Ishikawa
H
,
Kawakami
N
,
Kessler
RC
;
World Mental Health Japan Survey Collaborators
.
Lifetime and 12-month prevalence, severity and unmet need for treatment of common mental disorders in Japan: results from the final dataset of World Mental Health Japan Survey
.
Epidemiol Psychiatr Sci
.
2016
;
25
(
3
):
217
29
.
3.
Sado
M
,
Yamauchi
K
,
Kawakami
N
,
Ono
Y
,
Furukawa
TA
,
Tsuchiya
M
, et al
.
Cost of depression among adults in Japan in 2005
.
Psychiatry Clin Neurosci
.
2011
;
65
(
5
):
442
50
.
4.
Rush
AJ
,
Trivedi
MH
,
Wisniewski
SR
,
Nierenberg
AA
,
Stewart
JW
,
Warden
D
, et al
.
Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report
.
Am J Psychiatry
.
2006
;
163
(
11
):
1905
17
.
5.
O’Reardon
JP
,
Solvason
HB
,
Janicak
PG
,
Sampson
S
,
Isenberg
KE
,
Nahas
Z
, et al
.
Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial
.
Biol Psychiatry
.
2007
;
62
(
11
):
1208
16
.
6.
Sackeim
HA
,
Aaronson
ST
,
Carpenter
LL
,
Hutton
TM
,
Mina
M
,
Pages
K
, et al
.
Clinical outcomes in a large registry of patients with major depressive disorder treated with Transcranial Magnetic Stimulation
.
J Affect Disord
.
2020
;
277
:
65
74
.
7.
Lefaucheur
J-P
,
Aleman
A
,
Baeken
C
,
Benninger
DH
,
Brunelin
J
,
Di Lazzaro
V
, et al
.
Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): an update (2014-2018)
.
Clin Neurophysiol
.
2020
;
131
(
2
):
474
528
.
8.
Milev
RV
,
Giacobbe
P
,
Kennedy
SH
,
Blumberger
DM
,
Daskalakis
ZJ
,
Downar
J
, et al
.
Canadian network for mood and anxiety treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 4. Neurostimulation treatments
.
Can J Psychiatry
.
2016
;
61
(
9
):
561
75
.
9.
Fitzgerald
PB
,
George
MS
,
Pridmore
S
.
The evidence is in: repetitive transcranial magnetic stimulation is an effective, safe and well-tolerated treatment for patients with major depressive disorder
.
Aust N Z J Psychiatry
.
2022
;
56
(
7
):
745
51
.
10.
Baba
H
,
Kito
S
,
Nukariya
K
,
Takeshima
M
,
Fujise
N
,
Iga
J
, et al
.
Guidelines for diagnosis and treatment of depression in older adults: a report from the Japanese Society of mood disorders
.
Psychiatry Clin Neurosci
.
2022
;
76
(
6
):
222
34
.
11.
Carpenter
LL
,
Janicak
PG
,
Aaronson
ST
,
Boyadjis
T
,
Brock
DG
,
Cook
IA
, et al
.
Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of acute treatment outcomes in clinical practice
.
Depress Anxiety
.
2012
;
29
(
7
):
587
96
.
12.
Dowling
NL
,
Bonwick
R
,
Dharwadkar
NP
,
Ng
CH
.
Repetitive transcranial magnetic stimulation for major depression: a naturalistic observational study in an Australian private hospital
.
Psychiatry Res
.
2020
;
291
:
113275
.
13.
Kito
S
,
Miyazi
M
,
Nakatani
H
,
Matsuda
Y
,
Yamazaki
R
,
Okamoto
T
, et al
.
Effectiveness of high-frequency left prefrontal repetitive transcranial magnetic stimulation in patients with treatment-resistant depression: a randomized clinical trial of 37.5-minute vs 18.75-minute protocol
.
Neuropsychopharmacol Rep
.
2019
;
39
(
3
):
203
8
.
14.
Matsuda
Y
,
Kito
S
,
Igarashi
Y
,
Shigeta
M
.
Efficacy and safety of deep transcranial magnetic stimulation in office workers with treatment-resistant depression: a randomized, double-blind, sham-controlled trial
.
Neuropsychobiology
.
2020
;
79
(
3
):
208
13
.
15.
Borckardt
JJ
,
Nahas
ZH
,
Teal
J
,
Lisanby
SH
,
McDonald
WM
,
Avery
D
, et al
.
The painfulness of active, but not sham, transcranial magnetic stimulation decreases rapidly over time: results from the double-blind phase of the OPT-TMS Trial
.
Brain Stimul
.
2013
;
6
(
6
):
925
8
.
16.
Wang
WL
,
Wang
SY
,
Hung
HY
,
Chen
MH
,
Juan
CH
,
Li
CT
.
Safety of transcranial magnetic stimulation in unipolar depression: a systematic review and meta-analysis of randomized-controlled trials
.
J Affect Disord
.
2022
;
301
:
400
25
.
17.
Yamazaki
R
,
Inoue
Y
,
Matsuda
Y
,
Kodaka
F
,
Kitamura
Y
,
Kita
Y
, et al
.
Laterality of prefrontal hemodynamic response measured by functional near-infrared spectroscopy before and after repetitive transcranial magnetic stimulation: a potential biomarker of clinical outcome
.
Psychiatry Res
.
2022
;
310
:
114444
.
18.
Montgomery
SA
,
Asberg
M
.
A new depression scale designed to be sensitive to change
.
Br J Psychiatry
.
1979
;
134
:
382
9
.
19.
McCormack
HM
,
Horne
DJ
,
Sheather
S
.
Clinical applications of visual analogue scales: a critical review
.
Psychol Med
.
1988
;
18
(
4
):
1007
19
.
20.
Hunter
AM
,
Minzenberg
MJ
,
Cook
IA
,
Krantz
DE
,
Levitt
JG
,
Rotstein
NM
, et al
.
Concomitant medication use and clinical outcome of repetitive Transcranial Magnetic Stimulation (rTMS) treatment of major depressive disorder
.
Brain Behav
.
2019
;
9
(
5
):
e01275
.
21.
Inada
T
,
Inagaki
A
.
Psychotropic dose equivalence in Japan
.
Psychiatry Clin Neurosci
.
2015
;
69
(
8
):
440
7
.
22.
Razafsha
M
,
Barbour
T
,
Uribe
S
,
Behforuzi
H
,
Camprodon
JA
.
Extension of transcranial magnetic stimulation treatment for depression in non-responders: results of a naturalistic study
.
J Psychiatr Res
.
2023
;
158
:
314
8
.
23.
Hou
WH
,
Wang
TY
,
Kang
JH
.
The effects of add-on non-invasive brain stimulation in fibromyalgia: a meta-analysis and meta-regression of randomized controlled trials
.
Rheumatology
.
2016
;
55
(
8
):
1507
17
.
24.
Lefaucheur
JP
,
Drouot
X
,
Nguyen
JP
.
Interventional neurophysiology for pain control: duration of pain relief following repetitive transcranial magnetic stimulation of the motor cortex
.
Neurophysiol Clin
.
2001
;
31
(
4
):
247
52
.
25.
Rollnik
JD
,
Wüstefeld
S
,
Däuper
J
,
Karst
M
,
Fink
M
,
Kossev
A
, et al
.
Repetitive transcranial magnetic stimulation for the treatment of chronic pain - a pilot study
.
Eur Neurol
.
2002
;
48
(
1
):
6
10
.
26.
Lefaucheur
JP
.
Transcranial magnetic stimulation in the management of pain
.
Suppl Clin Neurophysiol
.
2004
;
57
:
737
48
.
27.
André-Obadia
N
,
Peyron
R
,
Mertens
P
,
Mauguière
F
,
Laurent
B
,
Garcia-Larrea
L
.
Transcranial magnetic stimulation for pain control. Double-blind study of different frequencies against placebo, and correlation with motor cortex stimulation efficacy
.
Clin Neurophysiol
.
2006
;
117
(
7
):
1536
44
.
28.
Borckardt
JJ
,
Reeves
ST
,
Weinstein
M
,
Smith
AR
,
Shelley
N
,
Kozel
FA
, et al
.
Significant analgesic effects of one session of postoperative left prefrontal cortex repetitive transcranial magnetic stimulation: a replication study
.
Brain Stimul
.
2008
;
1
(
2
):
122
7
.
29.
Taylor
JJ
,
Borckardt
JJ
,
Canterberry
M
,
Li
X
,
Hanlon
CA
,
Brown
TR
, et al
.
Naloxone-reversible modulation of pain circuitry by left prefrontal rTMS
.
Neuropsychopharmacology
.
2013
;
38
(
7
):
1189
97
.
30.
Che
X
,
Cash
RFH
,
Luo
X
,
Luo
H
,
Lu
X
,
Xu
F
, et al
.
High-frequency rTMS over the dorsolateral prefrontal cortex on chronic and provoked pain: a systematic review and meta-analysis
.
Brain Stimul
.
2021
;
14
(
5
):
1135
46
.
You do not currently have access to this content.