Effectiveness of high-frequency repetitive transcranial magnetic stimulation in patients with depression and Parkinson’s disease: a meta-analysis of randomized, controlled clinical trials

Figures & data

Figure 1 Flow diagram of the selection of the studies.

Table 1 Characteristics of studies included in meta-analysis

Study	Depression criteria/PD criteria	Country	Sample size (n)	Age (years)		Intervention		Outcome measure
				Sex M/F (n)
				Trial	Control	Trial	Control
Boggio et al, 2005^Citation34	DSM IV/UK brain bank criteria	USA	25	65.2±8.25 15/10		Focal rTMS of the left DLPFC; 15 Hz, 110% MT, 40 trains, 5 s on for 10 sessions for 2 weeks	Fluoxetine 20 mg/day for 8 weeks	1. HRSD 2. BDI 3. UPDRS-III
Brys et al, 2016^Citation23	DSM IV/UK brain bank criteria	USA	61	64.9±8.0 (DLPFC + M1), 59.6±12.6 (M1), 64.6±12.3 (DLPFC), 11/9, 9/5, 6/6 (sham)	64.0±7.4, 11/4	Focal rTMS of the DLPFC + M1/M1/left DLPFC; 10 Hz, 50 trains, 25 min for the left DLPFC and 12.5 min for M1 on for 10 sessions for 2 weeks	Sham rTMS	1. HRSD 2. BDI 3. UPDRS-III
Cardoso et al, 2008^Citation35	DSM IV/UK brain bank criteria	Brazil	21	67±8.3, no stated	63±7.1, no stated	Focal rTMS of the left DLPFC; 5 Hz, 120% MT, 50 trains, 15 s on for 12 sessions for 4 weeks	Fluoxetine 20 mg/day for 4 weeks	1. HRSD 2. BDI 3. UPDRS-III
Chen et al, 2011^Citation36	HRSD ≥13/no stated	China	49	60.70±8.9, 13/12	59.05±6.8 13/11	Focal rTMS of the left DLPFC; 5 Hz, 110% MT, 80 trains, interval 10 s for 16 sessions for 8 weeks	Paroxetine 20 mg/day for 8 weeks	1. HRSD 2. UPDRS-III
Fregni et al, 2004^Citation37	DSM IV/UK brain bank criteria	USA	42	65.3±7.8, 11/10	66.0±8.5, 15/6	Focal rTMS of the left DLPFC; 15 Hz, 110% MT, 40 trains, 5 s on for 10 sessions for 2 weeks	Fluoxetine 20 mg/day for 2 weeks	1. HRSD 2. BDI 3. UPDRS-III
Makkos et al, 2016^Citation25	DSM-IV-TR/UK brain bank criteria	Hungary	46	67 (60–73), 13/10	66 (62–70), 11/10	Focal rTMS of M1; 5 Hz, 90% MT, 12 trains, 10 s on for 10 sessions for 2 weeks	Sham-rTMS	1. MADRS 2. BDI 3. UPDRS-III
Pal et al, 2010^Citation22	DSM IV/UK brain bank criteria	Hungary	22	68.5 (59.5–70.0), 6/6	67.5 (57–72), 5/5	Focal rTMS of the left DLPFC; 5 Hz, 90% MT, 10 s on, 20 s off, 600 impulses/day for 10 days	Sham-rTMS	1. MADRS 2. BDI 3. UPDRS-III
Shin et al, 2016^Citation24	DSM IV/UK brain bank criteria	Korea	21	69 (55–82), 6/4	67 (54–79), 2/6	Focal rTMS of the left DLPFC; 5 Hz, 90% MT, 12 trains, 10 s on for 10 sessions for 2 weeks	Sham-rTMS	1. HRSD 2. MADRS 3. BDI 4. UPDRS-III
Wu et al, 2013^Citation20	HRSD ≥8/UK brain bank criteria	China	45	66.11±11.62, 11/11	65.69±10.28, 12/11	Focal rTMS of the left DLPFC; 10 Hz, 90%–100% MT, 1,740 pulse/d for 15 sessions for 3 weeks	Sham-rTMS	1. HRSD 2. UPDRS-III

Abbreviations: BDI, Beck Depression Inventory; DLPFC, dorsolateral prefrontal cortex; DSM-IV-TR, Diagnostic and Statistical Manual of Mental Disorders 4th-text revision edition; F, female; rTMS, repetitive transcranial magnetic stimulation; HF-rTMS, high-frequency rTMS; HRSD, Hamilton Rating Scale for Depression; M, male; M1, primary motor cortex; MT, motor threshold; MADRS, Montgomery-Åsberg Depression Rating Scale; SSRIs, selective serotonin reuptake inhibitors; UPDRS-III, Unified Parkinson’s Disease Rating Scale.

Figure 2 Risk of bias summaries for individual studies.

Figure 3 Risk of bias summaries for all studies.

Figure 4 Forest plots demonstrating summary effect estimates for depressive symptoms. Effect estimates derived using random-effects meta-analysis. Heterogeneity expressed as χ² and I².

Abbreviations: CI, confidence interval; rTMS, repetitive transcranial magnetic stimulation; HF-rTMS, high-frequency rTMS; IV, inverse variance; SSRIs, selective serotonin reuptake inhibitors; SMD, standardized mean difference.

Figure 5 Forest plots demonstrating summary effect estimates for motor symptoms. Effect estimates derived using random-effects meta-analysis. Heterogeneity expressed as χ² and I².

Abbreviations: CI, confidence interval; rTMS, repetitive transcranial magnetic stimulation; HF-rTMS, high-frequency rTMS; IV, inverse variance; MD, mean difference; SSRIs, selective serotonin reuptake inhibitors.

Figure S1 Forest plots demonstrating summary effect estimates for all-cause discontinuation. Effect estimates derived using random-effects meta-analysis. Heterogeneity expressed as χ² and I².

Abbreviations: CI, confidence interval; df, degrees of freedom; rTMS, repetitive transcranial magnetic stimulation; HF-rTMS, high-frequency rTMS; IV, inverse variance; SSRIs, selective serotonin reuptake inhibitors.

Figure S2 Forest plots demonstrating subgroup analysis according to the different rTMS site estimates for depressive symptoms. Effect estimates derived using random-effects meta-analysis. Heterogeneity expressed as χ² and I².

Abbreviations: DLPFC, dorsolateral prefrontal cortex; rTMS, repetitive transcranial magnetic stimulation; HF-rTMS, high-frequency rTMS; IV, inverse variance; M1, primary motor cortex; SMD, standardized mean differences; SSRIs, selective serotonin reuptake inhibitors.

Table

CENTRAL search strategy
#1. transcranial magnetic stimulation:ti,ab,kw or repetitive transcranial magnetic stimulation:ti,ab,kw or rTMS:ti,ab,kw or TMS:ti,ab,kw or noninvasive brain stimulation:ti,ab,kw	3144
#2. parkin*:ti	4723
#3. #1 and #2	124
PubMed search strategy
#1. Search (transcranial magnetic stimulation [Title/Abstract] OR repetitive transcranial magnetic stimulation [Title/Abstract] OR noninvasive brain stimulation [Title/Abstract] OR rTMS [Title/Abstract] OR TMS [Title/Abstract])	16257
#2. Search parkin*[Title]	57014s
#3. Search (transcranial magnetic stimulation[Title/Abstract] OR repetitive transcranial magnetic stimulation[Title/Abstract] OR noninvasive brain stimulation [Title/Abstract] OR rTMS [Title/Abstract] OR TMS [Title/Abstract]) AND parkin*[Title] Filters: Clinical Trial	90
Embase search strategy
#1. ‘transcranial magnetic stimulation’:ti,ab OR ‘repetitive transcranial magnetic stimulation’:ti,ab OR ‘noninvasive brain stimulation’:ti,ab OR rTMS:ti,ab OR TMS:ti,ab	21,836
#2. Parkin*:ti	80,218
#3. #1 AND #2	548
#4. #3 AND (‘clinical trial’/de OR ‘randomized controlled trial’/de)	87
PsycINFO search strategy
1. (“transcranial magnetic stimulation” or “repetitive transcranial magnetic stimulation” or “noninvasive brain stimulation” or rTMS or TMS).ti. or (“transcranial magnetic stimulation” or “repetitive transcranial magnetic stimulation” or “noninvasive brain stimulation” OR rTMS or TMS).ab.	7761
2. parkin*.ti.	16991
3. 1 and 2	152

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