Table 2:

Characteristics of Included Systematic Reviews

Author, Year Country	Literature Search Study Selection	No. of Studies	Population	Intervention	Comparators	Conclusion	ROBIS
Lepping et al, 201442 United Kingdom	Up to January 15, 2014 RCTs or non-RCTs (such as open-label or naturalistic trials)	21a	Inclusion: humans with a formal diagnosis of depression, irrespective of depression subtype or diagnostic criteria used Exclusion: studies where depression was not the primary diagnosis; adolescents or children	Inclusion: rTMS as monotherapy or add-on therapy Exclusion: nonstandard rTMS (e.g., deep TMS or stimulation outside the DLPFC)	Sham rTMS Another rTMS modality ECT	rTMS is superior to sham rTMS in treatment of TRD	High ROB
Zhang et al, 201543 China	Up to January 2014 RCTs	10	Inclusion: adults diagnosed with major depression according to DSM or ICD, patients who met TRD criteria (defined by failure to respond to at least one course of adequate treatment for major depression) Exclusion: TRD patients with comorbid neurological disorders and psychotic disorders or specific types of depression (e.g., child and adolescent depression or postpartum depression)	Inclusion: bilateral or unilateral rTMS	Sham rTMS Another rTMS modality	Clinical efficacy of bilateral rTMS was not significantly greater than of unilateral rTMS but is superior to sham TMS in people with TRD	Low ROB
Leggett et al, 201540 Canada	Up to January 10, 2014 RCTs	46a	Inclusion: adults (≥ 18 years of ageb) who have had TRD (≥ 2 previous treatments) or bipolar or unipolar depression Exclusion: not TRD or do not report whether patients have TRD	Inclusion: any form of rTMS	Sham rTMS Pharmacological therapyc Cognitive therapyc ECT Another modality of rTMS	rTMS is approximately twice as effective as sham TMS; however optimal rTMS modality remains unclear rTMS most likely as effective as ECT	Low ROB
Health Quality Ontario, 201618 Canada	Up to March 1, 2015 RCTs	30a	Inclusion: studies with adults ≥ 18 years of age; at least 80% of patients were resistant to treatment (TRD population), studies that included unipolar patients only or that reported the proportion of bipolar patients as ≤ 20% Exclusion: Studies of depression due to specific conditions (i.e., post-stroke depression, postpartum depression)	Inclusion: studies that applied HF rTMS (≥ 5 Hz) to left DLPFC (unilateral) and complied with safety guidelines; studies in which patients received at least 10 sessions of rTMS treatment Exclusion: studies with stimulation other than left DLPFC, used frequencies of rTMS outside range of this review, bilateral rTMS or bilateral vs. unilateral rTMS, sequential combined LF and HF rTMS, newer techniques (synchronized rTMS, pulsed rTMS, deep TMS, rTMS with priming stimulation)	Sham rTMS ECT	rTMS has small short-term effect compared with sham TMS on improving depression scores Significantly more improvement in depression scores with ECT than with rTMS	Low ROB
Nordenskjold et al, 201644 Sweden	Up to Nov 2014 Controlled studies with or without randomization	1	Inclusion: people with major depression or bipolar depression according to DSM or ICD criteria	Inclusion: H-coil deep TMS	Another treatmentc Sham deep TMS Different dose of deep TMSc	Evidence for deep TMS is considered insufficient for TRD	Low ROB
Berlim et al, 201745 Canada and United Kingdom	Jan 1, 2001, to Sept 6, 2016 RCTs, parallel or crossover trials	5	Inclusion: adults aged 18-75 years with a diagnosis of primary major depression (unipolar or bipolar) according to DSM or ICD criteria	Inclusion: Unilateral iTBS to the left DLPFC, unilateral cTBS to the right DLPFC, or consecutive iTBS/cTBS to the DLPFC given for ≥ 5 sessions either as monotherapy or as augmentation strategy for major depression	Sham TBS Pre-post active TBS	TBS (particularly cTBS and bilateral iTBS) is associated with substantial antidepressant effects, but researchers cannot draw definitive conclusions	Low ROB
Brunoni et al, 201746 Brazil and Canada	Up to Oct 1, 2016 RCTs	59	Inclusion: people with a primary diagnosis of an acute unipolar or bipolar depressive episode, including those who did not preclude comorbidities, such as anxiety or personality disorders Exclusion: studies with secondary mood disorders (e.g., post-stroke depression)	Inclusion: LF rTMS over the right DLPFC, HF rTMS over the left DLPFC, bilateral rTMS (LF over the right and HF over the left DLPFC), TBS (including iTBS over the left DLPFC, cTBS over the right DLPFC, or bilateral TBS), pTMS over the right DLPFC, aTMS over the left DLPFC, sTMS, deep TMS over the left DLPFC, and sham. Also, 1 Hz or less and 5 Hz or more defined LF and HF, respectively Exclusion: studies performing more than 10 rTMS sessions, using frequencies of 2–4 Hz	Sham rTMS Another rTMS modality	Few differences were found in clinical efficacy and acceptability between various rTMS modalities, favouring to some extent bilateral rTMS and priming LF rTMS, respectively	High ROB
University of Calgary, 201734 Canada	Up to Jan 10, 2014 RCTs	61a	Inclusion: adults (18 years or older) diagnosed with unipolar or bipolar depression with TRD (had ≥ 2 treatments) Exclusion: not TRD or do not report whether patients have TRD, not unipolar or bipolar depression	Inclusion: any form of rTMS Exclusion: not rTMS	Sham rTMS ECT Cognitive therapyc Pharmaceuticalsc Another rTMS modality	rTMS is effective when compared with sham rTMS. Optimal frequency, location, and intensity of rTMS are unclear Effectiveness of rTMS compared with ECT is unclear	Low ROB
Mutz et al, 201835 United Kingdom	Up to May 1, 2018 RCTs, parallel or crossover trials	33	Inclusion: adults aged 18–70 years, DSM or ICD diagnosis of major depression or bipolar disorder currently in a major episode Exclusion: primary diagnosis other than major depression or bipolar depression, studies limited to a specific subtype of depression	Inclusion: Any form of rTMS	Sham rTMS	HF left DLPFC rTMS was associated with improved rates of response compared with sham in people with TRD	Low ROB
Sehatzadeh et al, 201941 Canada	Up to Apr 3, 2017 RCTs	23	Inclusion: people who did not respond to treatment with antidepressant medications (TRD) diagnosed with unipolar depression, study populations that had less than 20% bipolar patients Exclusion: people with depression due to specific conditions (i.e., post-stroke depression, postpartum depression)	Inclusion: unilateral rTMS that applied HF rTMS to the left DLPFC, sequential bilateral rTMS that applied LF rTMS to the right DLPFC, and HF rTMS to the left DLPFC, had one treatment session daily and had at least 10 sessions Exclusion: novel rTMS interventions, studies that exceeded maximum allowed stimulation parameters set by safety guidelines	Sham rTMS	rTMS has moderate antidepressant effects for people with unipolar TRD	Low ROB

Abbreviations: aTMS, accelerated transcranial magnetic stimulation; cTBS, continuous theta burst stimulation; DLPFC, dorsolateral prefrontal cortex; DSM, Diagnostic and Statistical Manual of Mental Disorders; ECT, electroconvulsive therapy; HF, high frequency; ICD, International Classification of Diseases; iTBS, intermittent theta burst stimulation; LF, low frequency; pTMS, priming transcranial magnetic stimulation; RCT, randomized controlled trial; ROB, risk of bias; ROBIS, Risk of Bias in Systematic Reviews; rTMS, repetitive transcranial magnetic stimulation; sTMS, synchronized transcranial magnetic stimulation; TBS, theta burst stimulation; TMS, transcranial magnetic stimulation; TRD, treatment-resistant depression.

^aIncludes rTMS vs. sham or another rTMS modality and rTMS vs. ECT studies if the review included that comparator.

^bStudy also included youth but reported data separately.

^cDid not find any studies using this treatment as a comparator.