Transcranial magnetic stimulation in the treatment of obsessive–compulsive disorder: current perspectives

Figures & data

Figure 1 Search strategy.

Abbreviations: rTMS, repetitive transcranial magnetic stimulation; TMS, transcranial magnetic stimulation.

Table 1 rTMS over the right dlPFC

Low frequency (1 Hz)
Study	Study design	Baseline scores and definition of response	rTMS protocol parameters and baseline scores	Results	Duration of follow up and results	Limitations
Alonso et al^Citation37	18 patients medicated and unmedicated; 13 TR patients; RCT; mean age 35.2±12.1 years	Baseline YBOCS, active 24.0±5.3, sham group 25.6±6.1; response, global reduction in YBOCS ≥40%	18 sessions/3 x week/6 weeks; 20-minute sessions; 110% RMT; circular coil; neuronavigation; sham coil; 1 Hz at 20 RMT; time parameters same	NS difference between groups (P=0.081) at 10 weeks	10 weeks	Small sample, inclusion of TR subjects, medication synergy, use of circular coil
Seo et al^Citation39	27 TR patients; RCT; mean age 34.5±9.8 years active, 36.3±12.5 years sham; duration of illness 9.8–11.7±8–9.5 years	Baseline scores not reported; response, reduction in YBOCS scores ≥25%	15 sessions; 5 x week; 20-minute sessions; 1,200 pulses/day; 100% RMT; figure-eight coil; manual targeting	At 3 weeks, significant improvement in active vs sham YBOCS (P=0.008); NS difference on the responder rate in the active vs sham groups (P=0.148)	3 weeks	Small sample, lack of double-blinding, potential variable localization of targets due to manual targeting, HDRS scores not factored in, in the final results
Elbeh et al^Citation40	45 patients (3 groups of 15); double-blinded, randomized trial; mean duration of illness 19.2±11.5 months	1 Hz (baseline), YBOCS 26.7±6.5; 10 Hz, YBOCS 25.3±4.7; sham group, YBOCS 24.9±5.7; response rates not reported	2 weeks; 10 sessions; 1 Hz, 4 trains ×500 pulses/day, 40-second intertrain interval; 10 Hz: 10 trains ×200 pulses, 20-second intertrain interval, 100% RMT; sham rTMS, protocol identical to 10 Hz group, apart from position of coil; figure- eight coil	2 weeks, significant reduction in 1 Hz YBOCS (P=0.001)	3 months, significant reduction in 1 Hz vs sham (P=0.001); reduction in YBOCS between 1 Hz vs 10 Hz (P=0.019)	Heterogeneity of sample symptom dimension not explored. Small sample, unclear current medication status
High frequency (10 Hz)
Mansur et al^Citation41	27 patients (13 active rTMS, 14 sham); 6-week double-blind RCT + 6-week open-label trial in 10 patients; duration of illness 15.6–26.2 years	Baseline YBOCS, active 30±3, sham 29±4.9; response, YBOCS ≥30% reduction + “much or very much improved” CGI	Initial 6 weeks, 30 sessions, 40 trains; 5-second trains + 25-second intertrain interval, 60,000 pulses; 110% RMT; figure- eight coil; manual targeting; sham, deactivated coil	No significant difference after 6 weeks of initial treatment between groups (P=0.71)	Additional 6-week open- label trial for 10 patients from the previous sham group; week 8, YBOCS, P=0.023; effect lost after week 8	Small sample, imprecision linked to manual targeting, severity and long duration of illness
Elbeh et al^Citation40	45 patients, 3 groups of 15 patients; double- blind, randomized trial; mean duration of illness 19.2±11.5 months	1 Hz baseline YBOCS 26.7±6.5; 10 Hz YBOCS 25.3±4.7; sham group YBOCS 24.9±5.7; response rates not reported	2 weeks; 10 sessions; 1 Hz, four trains, 500 pulses/day; 40-second intertrain interval; 10 Hz, 10 trains, 200 pulses/day; 20-second intertrain interval, 100% RMT; sham rTMS, protocol identical to the 10 Hz group, apart from the position of coil; figure-eight coil	2 weeks, significant reduction YBOCS 1 Hz (P=0.001)	3 months, significant reduction in 1 Hz vs sham (P=0.001); reduction in YBOCS scores in 1 Hz vs 10 Hz (P=0.019)	Heterogeneity of sample symptom dimension not explored, small sample, unclear current medication status

Abbreviations: rTMS, repetitive transcranial magnetic stimulation; CGI, Clinical Global Impression; dlPFC, dorsolateral prefrontal cortex; YBOCS, Yale–Brown Obsessive–Compulsive Scale; RMT, resting motor threshold; NS, nonsignificant; RCT, randomized controlled trial; HDRS, Hamilton Depression Rating Scale; TR, treatment-resistant.

Table 2 LF and HF rTMS over the left dlPFC

Low-frequency (1 Hz) rTMS over the left dlPFC
Study	Study design	Baseline scores and definition of response	rTMS protocol parameters and baseline scores	Results	Duration of follow up and results	Limitations
Prasko et al^Citation42	30 TR OCD patients; RCT; active vs sham; age 28.9–33.4 years, mean duration of illness ~15 years	YBOCS, active 29.82±5.8, sham 23.42±4.9; response definition NA	2 weeks, 30-minute sessions, 1,800 pulses/session; 110% RMT; sham stimulation, same parameters at 90° over the left dlPFC; figure-eight coil; manual targeting	2 weeks; NS difference between groups	4 weeks, NS effects on YBOCS, CGI-S, HARS between groups	Small sample, baseline difference on YBOCS scores between active and sham groups, manual targeting of left dlPFC, active sham coil
High-frequency (>5 Hz) rTMS over the left dlPFC
Sachdev et al^Citation43	18 TR OCD patients; 2-week RCT + 2-week open-label study; mean age, active 29.5±9.9 years, sham 35.8±8.2 years; duration of illness, active 12.6±7.5 years, sham 12.3±5.4 years	Baseline YBOCS, active 25.8±5.7, sham 23.9±9.9; clinically significant improvement definition, reduction in YBOCS ≥40%	10 sessions/2 weeks–20 sessions/4 weeks; each session 30 trains ×5 seconds + 25-second intertrain interval; 110% RMT; manual targeting	NS at 2 weeks (P=0.76)	NS at 4 weeks (P=0.24); clinically significant improvement in 6 patients	Small sample, TR illness in chronic OCD patients

Abbreviations: rTMS, repetitive transcranial magnetic stimulation; dlPFC, dorsolateral prefrontal cortex; TR, treatment-resistant; OCD, obsessive–compulsive disorder; RCT, randomized controlled trial; YBOCS, Yale–Brown Obsessive–Compulsive Scale; NA, not applicable; RMT, resting motor threshold; NS, nonsignificant; CGI-S, Clinical Global Impression – severity; HARS, Hamilton Anxiety Rating Scale.

Table 3 Stimulation of bilateral dlPFC

Study	Study design	Baseline scores and definition of response	rTMS protocol parameters	Results	Duration of follow up and results	Limitations
HF α-guided rTMS
Ma et al^Citation44	46 patients in active and control groups; RCT; age, active 27.12±8.97 years, sham 29.86±9.42 years; duration of illness, active 11.40±5.65 years, sham 12.48±5.34 years	YBOCS, active 25.4±6.2, control 23.4±5.7; definition of response, CGI 1 to ≥2, <35% YBOCS, remission, YBOCS <16	2 weeks; 20-minute sessions; 4-second train + 56-second intertrain interval/minute; circular coil; manual targeting; inactive sham coil; same protocol	At 2 weeks, reduction in total YBOCS and obsessive scores, active vs sham (P=0.001); response to treatment, active vs sham (P<0.01)	At 3 weeks, group difference in YBOCS (P<0.05); response to treatment, active vs sham (P<0.05)	Use of circular coil, manual targeting
HF (>5 Hz) rTMS of bilateral dlPFC
Haghighi et al^Citation45	21 TR OCD patients; single- blind crossover RCT; mean age 35.8 years; unknown duration of illness	First active rTMS group YBOCS 30.40±6.54; first sham rTMS YBOCS 30.09±8.08; definition of response, Pallanti and Quercioli^Citation14	20 Hz; 2 weeks active + 2 weeks sham rTMS; stimulation of left then right dlPFC with same parameters; 750 pulses; 25 trains with 1.5 seconds duration intertrain interval; 100% RMT; figure-eight coil; manual targeting; coil 45°–90° to the skull	2-week improvement in YBOCS for active, but not sham (P<0.001)	At 4 weeks, full and partial responses to treatment, active vs sham (P=0.002/P=0.003)	Small sample, single-blind study design, unknown duration of illness
Jahangard et al^Citation46	10 patients; single-blind RCT crossover design; mean age 33.1 years; unknown duration of illness	Baseline YBOCS, active group 31±2.25, sham group 31±2.25	20 Hz; 2 weeks active + 2 weeks sham rTMS; stimulation of left then right dlPFC with same parameters: 750 pulses; 25-second train + 1.5- second intertrain interval; 100% RMT; figure-eight coil; manual targeting; coil 45°–90° to the skull	At 2 weeks, decrease in YBOCS for active-then- sham group (P<0.01) + improvement in cognitive performances	At 4 weeks, sham- then-active group had significant decrease in YBOCS (P<0.01)	Small sample; single-blind study design; unknown duration of illness; active sham coil
Low-frequency (1 Hz) sequential rTMS over dlPFC and SMA
Kang et al^Citation47	21 TR OCD patients; RCT; active vs sham; age, active 28.60±12.66 years, sham 26.20±10.52 years; duration of illness, active 8.17±3.81 years, sham 9.46±9.41 years	Baseline YBOCS, active 26.50±5.64, sham 26.30±4.06	10 days; 1 Hz for 10 minutes on right dlPFC, 1,200 stimuli/day 110% RMT + 1 Hz for 10 minutes on SMA; 1,200 stimuli/day; 100% RMT; figure-eight coil; 45° coil-tilt method	4 weeks; NS difference between groups; YBOCS P=0.92; NS difference for depression (MADRS, P=0.67) or anxiety (HARS, P=0.84) scales	4 weeks	Active sham conditions, small sample, TR OCD patients

Abbreviations: dlPFC, dorsolateral prefrontal cortex; CGI, Clinical Global Impression; rTMS, repetitive transcranial magnetic stimulation; HF, high-frequency; RCT, randomized controlled trial; YBOCS, Yale–Brown Obsessive–Compulsive Scale; TR, treatment-resistant; OCD, obsessive–compulsive disorder; RMT, resting motor threshold; SMA, supplementary motor area; NS, nonsignificant; MADRS, Montgomery–Åsberg Depression Rating Scale; HARS, Hamilton Anxiety Rating Scale.

Table 4 LF rTMS over the SMA

Study	Study design	Baseline scores and definition of response	rTMS-protocol parameters	Results	Duration of follow up and results	Limitations
Mantovani et al^Citation60	21 patients, (9 active rTMS, 9 sham rTMS); 4-week RCT and 4-week open-label; age, active 39.7±8.6 years, sham, 39.4±10.2 years; duration of illness, active 22.4±13.8 years, sham 22.1±7.3 years	YBOCS, active 26±5.4, sham 26.7±5.5; response definition, patients with 25% YBOCS reduction at the end of phase 1	8 weeks; 1 Hz; SMA; figure-eight coil; mapping via international 10–20 EEG system; phase 1, active vs sham rTMS 4 weeks, 5 days/week; 20-minute train/session; 1,200 pulses/day; 100% RMT; phase 2, 4-week open-label rTMS to nonresponders to sham and responders and nonresponders to active rTMS in phase 1	NS response rate between active and sham groups at week 2 and week 4 (P=0.294, P=0.153); at 4 weeks, active vs sham YBOCS NS; active vs sham YBOCS SR P=0.031	8 weeks; phase 2; control vs active, significant effect of time on YBOCS (P=0.000); sham vs active, NS YBOCS change; at 3 months, six responders to active rTMS showed a 51% decrease from baseline YBOCS	Small sample, “imperfect” sham system, potential synergistic effect with medication
Gomes et al^Citation62	22 patients; double-blind RCT; active rTMS 12, sham rTMS 10; mean age, active 35.5±7.5 years + duration of illness 17±8 years; sham, age 37.5±16 years; duration of illness 19.5±12 years	Active YBOCS 36.4±3.2, sham YBOCS 31.8±3.5; responders, patients with 25% YBOCS reduction	2 weeks; 1 Hz; 5 days a week; 20-minute trains; 1,200 pulses/day; figure-eight coil; 100% RMT; bilateral pre-SMA localized via international 10–20 EEG system	Week 2, significant reduction in YBOCS between active and sham (P=0.0076); response rate, active vs sham P<0.001	14 weeks; YBOCS active vs sham P<0.0001; response rate, active vs sham P<0.001	Small sample, limitations in sham design, synergy with medications, manual navigation system
Arumugham et al^Citation63	34 treatment-refractory OCD patients; active vs sham rTMS; RCT; baseline demographic data not reported	Baseline data not reported; definition of response NA	3 weeks, 18 days; 1 Hz; 1,200 pulses/day; pre-SMA; process of targeting NA; coil description NA	Week 3, NS difference between active and sham rTMS (P=0.972)	12 weeks – results NA	Description of sham rTMS NA, stimulation protocol and duration of pulse intervals NA
Hawken et al^Citation64	22 patients; multicenter double- blind RCT; age, active 33±11 years, sham 34±14 years; duration of illness, center B vs center T, P=0.037	Center B, YBOCS 28±5; center T, YBOCS 28±4; responders, YBOCS reduction >25%	6 weeks; 1 Hz; 5 days a week for 4 weeks, then 3 days a week for 1 week and 2 days a week for 1 week 20-minute sessions (5-minute trains and 2-minute intertrain intervals); figure-eight coil; 110% RMT; bilateral SMA localized via international 10–20 EEG system; active tilted coil 90° from the skull; 110% RMT	Significant effect; after 5 weeks (25 treatments), YBOCS active vs sham P=0.023	8 weeks; significant effect; 2 weeks after last treatment, YBOCS active vs sham P=0.044	Small sample, potential blinding issue with sham treatment due to imperfect sham design, multicenter design with significant difference in the duration of illness between sites
Pelissolo et al^Citation65	36 patients with YBOCS >15, >2 years of illness and 8 weeks of nonresponse to two SSRIs; 75% with comorbid MDD; age 41.5±10.7 years; duration of illness, active 19.8±12.8 years, sham 24±10.9 years	YBOCS, active 30.2±4.2, sham 28.6±4.6; unclear definition of responders	4 weeks; 1 Hz; 26-minute sessions; 4/5-minute trains with 2-minute rest; 1,500 pulses/day; figure-eight coil; 100% RMT; bilateral pre-SMA; T1 MRI neuronavigation; sham rTMS, Magstim sham coil	NS differences between active and sham at week 4	NS difference over 12 weeks	Comorbidity with depressive symptoms

Abbreviations: LF, low-frequency; rTMS, repetitive transcranial magnetic stimulation; SMA, supplementary motor area; RCT, randomized controlled trial; YBOCS, Yale–Brown Obsessive–Compulsive Scale; EEG, electroencephalography; RMT, resting motor threshold; NS, nonsignificant; SR, self-report; OCD, obsessive–compulsive disorder; NA, not available; SSRIs, selective serotonin-reuptake inhibitors; MDD, major depressive disorder; MRI, magnetic resonance imaging.

Table 5 LF rTMS stimulation of OFC

Study	Study design	Baseline scores and definition of response	rTMS protocol parameters	Results	Duration of follow up and results	Limitations
Ruffini et al^Citation67	23 TR OCD patients; active vs sham; baseline YBOCS scores >30 in both groups; age NA; duration of illness NA	Baseline YBOCS scores >30 in both groups; response definition not stated	15 days/15 sessions; 10-minute sessions; 1 Hz; left OFC; figure-eight coil; manual targeting; 80% RMT; sham coil, inactive rTMS coil placed perpendicularly to the left OFC	15 days; active vs sham P<0.04	3 months; significant difference until week 10 (P<0.06)
Nauczyciel et al^Citation68	19 TR OCD patients; RCT crossover design; on–off 39 (24–56); off–on 40 (24–56)	On–off YBOCS 32 (15–36); off–on 32 (16–36); level of response not measured	10 sessions/2 × day in the first week; 1 Hz; 120% RMT; 1,200 pulses/session; right OFC; D8-80 butterfly double- cone coil; sham coil placebo	YBOCS active vs sham P=0.07	35 days; active vs sham YBOCS P=0.94	Small sample, design prone to unblinding

Abbreviations: LF, low-frequency; rTMS, repetitive transcranial magnetic stimulation; OFC, orbitofrontal cortex; TR, treatment-resistant; OCD, obsessive–compulsive disorder; YBOCS, Yale–Brown Obsessive–Compulsive Scale; NA, not available; RMT, resting motor threshold; RCT, randomized controlled trial.

Table 6 HF and LF stimulation via dTMS

Study	Study design	Baseline scores and definition of response	rTMS protocol parameters and baseline scores	Results	Duration of follow up and results	Limitations
Carmi et al^Citation72	Double-blind, controlled trial; 41 OCD patients; sham 20 Hz, active 1 Hz; + simultaneous with symptom provocation; age 28±3.1 years, 35±3.5 years, 36±2.1 years	Baseline YBOCS 25–28	5 weeks; 1 Hz/20 Hz; targeting mPFC, including ACC; LF, 1 Hz, 110% RMT, 900 pulses; HF, 20 Hz, 100% RMT, 50 2-second trains (2,000 pulses); H7 coil; sham coil NA	At 5 weeks, 20 Hz dTMS vs 1 Hz dTMS P=0.0243	At 3 months, stability in improvements measured by YBOCS	Accessibility of specific coil for general use; particular stimulation protocol linked with symptom provocation

Abbreviations: HF, high-frequency; LF, low-frequency; dTMS, deep transcranial magnetic stimulation; OCD, obsessive–compulsive disorder; YBOCS, Yale–Brown Obsessive–Compulsive Scale; rTMS, repetitive TMS; mPFC, medial prefrontal cortex; ACC, anterior cingulate cortex; RMT, resting motor threshold; NA, not available.

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