Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research

Probably not a substantial claim: may not pass S3 (load-bearing).

Two included studies included a bilateral standard rTMS comparison condition.

“Two studies (Blumberger et al., 2022;Fitzgerald et al., 2020) included a bilateral standard rTMS comparison condition.”

• cites Blumberger et al., 2022 sourceSupported
• cites Fitzgerald et al., 2020 sourceDisputed

  The study did include a standard rTMS comparison arm (Study design, §2.1), but our copy describes stimulation in that arm as applied to the left side (treatment description reproduced near §4). The Treatment section (§2.4) also identifies the F3 site. This contradicts the claim that this study’s standard rTMS comparison was bilateral; the cited passages provide no page numbers. (LLM, conf=0.84)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

May combine two claims.

Neurocognitive impairment is a common feature of MDD and is strongly associated with disability, quality of life, and overall functioning.

“Given that neurocognitive impairment is a common feature of MDD that is associated with overall functioning”

• Also stated in: § 1. Background · boosted

  “Neurocognitive dysfunction is a common feature of depression (Hammar et al., 2022;Porter et al., 2003;Zakzanis et al., 1999) and is strongly associated with disability, quality of life, and overall functioning (Evans et al., 2014;Gonda et al., 2015;Jaeger et al., 2006;Naismith et al., 2007).”

• cites Hammar et al., 2022 sourceSupported
• cites Porter et al., 2003 sourcePartly supported

  The Abstract says neurocognitive impairment has been widely reported in MDD, and the Discussion reports significant impairment in the young adult out-patients studied. Neither passage establishes an association with overall functioning; the supplied copy also does not support the quoted additions about disability or quality of life (searched those terms and functional outcomes). (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Zakzanis et al., 1999Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Robust evidence has demonstrated the safety and tolerability of rTMS and has suggested that it is superior to sham stimulation on variables of depression severity, response, and remission in adults across the lifespan.

“Robust evidence (e.g., Wallman et al., 2022;Zis et al., 2020) has demonstrated the safety and tolerability of rTMS and has suggested that it is superior to sham stimulation on variables of depression severity, response, and remission in adults across the lifespan (Adu et al., 2022;De Risio et al., 2020;Gaynes et al., 2014).”

• cites Wallman et al., 2022 sourceNot checked — no full text of the source
• cites Zis et al., 2020 sourceSupported
• cites Adu et al., 2022 sourcePartly supported

  The Results table (§3.8; page unavailable) reports greater improvement in depression severity with active rTMS than sham in one adult trial, and higher remission with bilateral rTMS than sham in an older-adult trial. The Discussion (§4; page unavailable) describes rTMS as safe and tolerable for treatment-resistant depression. But the review also reports sham-controlled trials with no significant difference in severity, response, or remission, so it does not support the unqualified suggestion of superiority across adult ages and all three outcomes. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Repetitive transcranial magnetic stimulation (rTMS) was cleared by the U.S. Food and Drug Administration (FDA) in 2008 as a treatment for major depressive disorder (MDD).

“Repetitive transcranial magnetic stimulation (rTMS) was cleared by the U.S. Food and Drug Administration (FDA) in 2008 as a treatment for major depressive disorder (MDD).”

• Also stated in: § 1. Background · plain

  “rTMS repeated daily for four to six weeks as a treatment for TRD was cleared by the United States Food and Drug Administration (FDA) in 2008 and is widely used in clinical settings (McClintock et al., 2017;Perera et al., 2016;Trapp et al., 2025).”

• cites McClintock et al., 2017Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Perera et al., 2016 sourceSupported
• cites Trapp et al., 2025 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Evidence varies regarding the domain most impacted by depression across the lifespan and includes executive function, processing speed, and verbal memory.

“Although some have demonstrated that individuals experiencing depression perform worse across all neurocognitive domains (e.g., Bora et al., 2013;Parkinson et al., 2020), evidence varies regarding the domain most impacted by depression across the lifespan and include executive function (Alexopoulos, 2021), processing speed (Göke et al., 2024), and verbal memory (Bora et al., 2013;Goodall et al., 2”

• cites Alexopoulos, 2021 sourceNot checked — no full text of the source
• cites Göke et al., 2024Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Bora et al., 2013 sourcePartly supported

  The Cognitive domains section reports that healthy controls outperformed euthymic MDD patients in every cognitive domain examined. The Discussion identifies verbal memory as a particularly pronounced deficit in patients whose depression began late in life. The citing sentence extends these findings to people experiencing depression generally, whereas this meta-analysis concerns patients in remission. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

While the neurocognitive effects of some new TBS protocols have been consistently investigated, others have not.

“Further, while the neurocognitive effects of some new TBS protocols have been consistently investigated (e.g., SNT Cole et al., 2019;Cole et al., 2022;Cole et al., 2020), others have not (e.g., prolonged iTBS Li et al., 2020;Richard et al., 2022).”

• cites Cole et al., 2019 sourceSupported
• cites Cole et al., 2022 sourceNot checked — no full text of the source
• cites Cole et al., 2020 sourceNot checked — no full text of the source

May combine two claims.

Numerous studies of TBS for TRD have been published, but studies tend to report reduction in depressive symptoms as the sole outcome measure, focus on neuroimaging, or report other clinical outcomes.

“Numerous studies of TBS for TRD have been published, but studies tend to report reduction in depressive symptoms as the sole outcome measure (e.g., Bakker et al., 2015;Blumberger et al., 2018;Blumberger et al., 2021;Bouaziz et al., 2023;Bulteau et al., 2022;Caeyenberghs et al., 2018;Chen et al., 2021;Lee et al., 2021;Mehta et al., 2022;Spitz et al., 2022;Spurny-Dworak et al., 2022;Stöhrmann et al.”

• cites Bakker et al., 2015 sourcePartly supported

  The Results (page unavailable) report reduced depressive symptoms in the iTBS group on the HamD17 and BDI-II scales. But the Results also report safety and tolerability outcomes, including adverse events and premature discontinuation, so symptom reduction was not the sole outcome reported by this study. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites Blumberger et al., 2018 sourceNot checked — no full text of the source
• cites Blumberger et al., 2021 sourcePartly supported

  The Results (§3.1) report reduced depressive-symptom scores in both treatment groups, so this paper supports that part of the citation. But the Procedures (§2.2) also identify adverse events, pain intensity, serious adverse events, and treatment discontinuation as reported outcomes; depressive symptoms were not the sole outcome measure. Page numbers were not available in our copy. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Neurocognitive dysfunction is commonly reported during depressive episodes and even during remission.

“Neurocognitive dysfunction is commonly reported during depressive episodes and even during remission (Bora et al., 2013;Conradi et al., 2011;Hasselbalch et al., 2011).”

• cites Bora et al., 2013 sourceSupported
• cites Conradi et al., 2011 sourceSupported
• cites Hasselbalch et al., 2011 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Evidence suggests that pharmacotherapy may improve neurocognitive function; however, the degree of improvement appears modest and efficacy varies by medication class and neurocognitive domain.

“Evidence suggests that pharmacotherapy may improve neurocognitive function; however, the degree of improvement appears modest and efficacy varies by medication class and neurocognitive domain (Baune and Renger, 2014;Keefe et al., 2014).”

• cites Baune and Renger, 2014 sourceNot checked — no full text of the source
• cites Keefe et al., 2014 sourcePartly supported

  The Results report cognitive improvements that were relatively small compared with the deficits, and the Discussion describes possible benefits that differ by cognitive domain. The Results also compare individual medications, but the paper does not establish that efficacy varies by medication class; the Discussion cautions that firm conclusions about differential effects across domains are difficult to draw. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

Some evidence suggests heterogenous profiles of neurocognitive dysfunction among individuals experiencing depression and that treatment resistance may drive the existence of subgroups with particularly high levels of dysfunction.

“Some evidence suggests that there are heterogenous profiles of neurocognitive dysfunction among individuals experiencing depression (Martin et al., 2020) and that treatment resistance may drive the existence of subgroups with particularly high levels of dysfunction (Vicent-Gil et al., 2021).”

• cites Martin et al., 2020 sourceSupported
• cites Vicent-Gil et al., 2021 sourceSupported

Probably not a substantial claim: may not pass S2 (checkable).

Taken together, these findings highlight the need for neurocognitive functioning to be a key target of treatment for depression.

“Taken together, these findings highlight the need for neurocognitive functioning to be a key target of treatment for depression (Gonda et al., 2015;Kaser et al., 2017).”

• cites Gonda et al., 2015 sourceSupported
• cites Kaser et al., 2017 sourceSupported

May combine two claims.

While the neurocognitive effects of standard rTMS have been well-studied, a dearth of evidence exists related to neurocognition in TBS for TRD.

“While the neurocognitive effects of standard rTMS have been wellstudied (Gregory et al., 2022;Schulze-Rauschenbach et al., 2005;Yildiz et al., 2023), a dearth of evidence exists related to neurocognition in TBS for TRD.”

• cites Gregory et al., 2022 sourceNot checked — no full text of the source
• cites Schulze-Rauschenbach et al., 2005 sourcePartly supported

  The Neuropsychological effects section reports cognitive testing after rTMS, so this paper supports the claim that standard rTMS has been studied for neurocognitive effects. But the Background says no prior study had addressed its differential cognitive impact versus ECT, and the Limitations call this study's findings preliminary; the paper does not establish that those effects were already well studied. The citation is attached to the rTMS clause, not the claim about a lack of TBS evidence. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites Yildiz et al., 2023 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Executive function significantly impacts overall functioning.

“and significantly impacts overall functioning (Diamond, 2013).”

• cites Diamond, 2013 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Evidence suggests newer antidepressants may be superior to prior medication classes (e.g., tricyclics, MAOIs) in neurocognitive effects.

“Nonetheless, evidence suggests they may be superior to prior medication classes (e.g., tricyclics, MAOIs; Baune & Renger, 2014;Stein & Strickland, 1998).”

• cites Baune & Renger, 2014 sourceNot checked — no full text of the source
• cites Stein & Strickland, 1998 sourcePartly supported

  The SSRIs section says SSRIs produce smaller cognitive-performance decrements than tricyclic antidepressants. But the MAO Inhibitors section says there is insufficient research for a direct comparison with SSRIs and expects the two classes to have comparable overall cognitive effects. The claimed advantage over MAOIs is therefore not supported. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

The systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

“A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Page et al., 2021).”

• cites Page et al., 2021 sourceSupported

May combine two claims.

Blumberger et al. (2022) found no significant within- or between-groups differences on MoCA total scores.

“Blumberger et al. (2022) found no significant within-or between-groups differences on the Montreal Cognitive Assessment (MoCA) total scores.”

• cites Blumberger et al., 2022 sourcePartly supported

  Methods > Safety and Tolerability Measures identifies the Montreal Cognitive Assessment as a measure of global cognition. Results > Cognitive Safety reports no significant between-group differences on any cognitive measure, which includes MoCA, and no substantial changes on those measures. It does not explicitly report a statistical test finding no significant within-group change in MoCA total scores; “no substantial changes” is not necessarily the same finding. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

May combine two claims.

Cognitive dysfunction is a core symptom of depression that can persist during the remitted state, worsens with increasing numbers of depressive episodes, and results in disrupted psychosocial functioning.

“As cognitive dysfunction is a core symptom of depression that can persist during the remitted state (Bora et al., 2013;Hasselbalch et al., 2011;Kaser et al., 2017), worsens with increasing numbers of depressive episodes (Hasselbalch et al., 2013), and results in disrupted psychosocial functioning (Hasselbalch et al., 2011;Kaser et al., 2017;McCall and Dunn, 2003)”

• cites Bora et al., 2013 sourceSupported
• cites Hasselbalch et al., 2011 sourceNot checked — no full text of the source
• cites Kaser et al., 2017 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

NIH Toolbox cognitive measures were used in three studies.

“The NIH Toolbox cognitive measures were also used in three studies (Blumberger et al., 2022;Cristancho et al., 2020;Cristancho et al., 2023).”

• cites Blumberger et al., 2022 sourceSupported
• cites Cristancho et al., 2020 sourceNot checked — no full text of the source
• cites Cristancho et al., 2023 sourceNot checked — no full text of the source

May combine two claims.

A follow-up study by Cristancho et al. (2023) and a study by Blumberger et al. (2022) failed to replicate the earlier finding of significant improvement on the Flanker Inhibitory Control and Attention Test.

“but a follow up study by Cristancho et al. (2023) and a study by Blumberger et al. (2022) failed to replicate that earlier finding.”

• cites Cristancho et al., 2023 sourceNot checked — no full text of the source
• cites Blumberger et al., 2022 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Three studies used subtests of the D-KEFS.

“Three studies (Blumberger et al., 2022;Cole et al., 2020;Cole et al., 2022) used subtests of the D-KEFS.”

• cites Blumberger et al., 2022 sourceSupported
• cites Cole et al., 2020 sourceNot checked — no full text of the source
• cites Cole et al., 2022 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Other reviews have suggested TBS is an effective treatment for reducing mood symptoms among individuals experiencing TRD.

“while other reviews have suggested TBS is an effective treatment for reducing mood symptoms among individuals experiencing TRD (Voigt et al., 2021)”

• cites Voigt et al., 2021 sourceSupported

May combine two claims.

Blumberger et al. (2022) found no within- or between-group differences on the CVLT-II.

“Blumberger et al. (2022) found no within-or between-group differences on the California Verbal Learning Test-2nd edition (CVLT-II).”

• cites Blumberger et al., 2022 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Robust evidence exists regarding the use of vortioxetine to treat mood-related symptoms of depression and slowed processing speed, and it is the only FDA-cleared psychotropic medication to treat both.

“Robust evidence exists regarding the use of vortioxetine to treat mood-related symptoms of depression and slowed processing speed (Bennabi et al., 2019;Frampton, 2016;Harrison et al., 2016;Mahableshwarkar et al., 2015;McIntyre et al., 2014), and it is the only FDA-cleared psychotropic medication to treat both.”

• cites Bennabi et al., 2019 sourceSupported
• cites Frampton, 2016 sourceNot checked — no full text of the source
• cites Harrison et al., 2016 sourcePartly supported

  The Results and Discussion report that vortioxetine improved attention and speed of processing in adults with major depressive disorder. The paper does not establish the cited clause’s claim about treating mood-related symptoms specifically. The FDA-cleared assertion follows the citation rather than being directly attributed to it. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Evidence supports pro-cognitive effects of TMS in healthy individuals and in patients with neurologic and psychiatric illnesses such as mild to moderate Alzheimer's disease, mild cognitive impairment, stroke, schizophrenia, and bipolar disorder.

“Evidence supports the pro-cognitive effects of TMS in healthy individuals (Luber & Lisanby, 2014) and in patients with neurologic and psychiatric illnesses such as mild to moderate Alzheimer's disease (Cheng et al., 2018;Chou et al., 2020;Lin et al., 2019;Wang et al., 2020), mild cognitive impairment (MCI; Chou et al., 2020;Drumond Marra et al., 2015;Jiang et al., 2021), stroke (M.Liu et al., 2021”

• cites Luber & Lisanby, 2014 sourceSupported
• cites Cheng et al., 2018 sourceNot checked — no full text of the source
• cites Chou et al., 2020 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

In five included studies, participants received bilateral TBS.

“In five studies (Blumberger et al., 2022;Cheng et al., 2016;Cristancho et al., 2020;Cristancho et al., 2023;Holczer et al., 2021), participants received bilateral TBS.”

• cites Blumberger et al., 2022 sourceSupported
• cites Cheng et al., 2016 sourceNot checked — no full text of the source
• cites Cristancho et al., 2020 sourceNot checked — no full text of the source

May combine two claims.

Subjective cognitive concerns are common in clinical settings and may be related to depressive symptomatology, real-world functioning, and quality of life.

“Subjective cognitive concerns are common in clinical settings and may be related to depressive symptomatology, real-world functioning, and quality of life (Allott et al., 2020;Brigola et al., 2015;McIntyre et al., 2014;Sumiyoshi et al., 2021).”

• cites Allott et al., 2020 sourceSupported
• cites Brigola et al., 2015 sourcePartly supported

  The Discussion says subjective memory complaints are common in the elderly, and the Results link them to depression, lower quality of life, and limitations in daily activities. The paper also discusses memory-clinic patients, but it does not establish that subjective cognitive concerns are common across clinical settings or populations beyond older adults. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites McIntyre et al., 2014 sourcePartly supported

  The Introduction (page not provided) describes frequent subjective cognitive complaints in major depression and links cognitive dysfunction to impaired workplace functioning. The Discussion (page not provided) also notes that patients can report impaired concentration despite symptom-based remission. The paper does not address quality of life directly, and its discussion of common complaints is specific to depression rather than clinical settings generally. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

When alternate forms are used and/or reliable change indices are employed, practice effects may be reduced and better understood.

“however, when alternate forms are used and or reliable change indices are employed, these practice effects may be reduced and better understood (Beglinger et al., 2005;Benedict and Zgaljardic, 1998).”

• cites Beglinger et al., 2005 sourceSupported
• cites Benedict and Zgaljardic, 1998 sourceNot checked — no full text of the source

May combine two claims.

Positive functional outcomes of individuals with TRD are hampered by lingering neurocognitive dysfunction that decreases intervention efficacy and increases relapse.

“Positive functional outcomes of individuals with TRD are hampered by lingering neurocognitive dysfunction that decreases intervention efficacy (Alexopoulos et al., 2015;Gonda et al., 2015;Story et al., 2008) and increases relapse (Alexopoulos, 2021;Gonda et al., 2015;Manning et al., 2015).”

• cites Alexopoulos et al., 2015 sourcePartly supported

  The Discussion (page not provided) reports that older adults with major depression who performed poorly on cognitive-control tasks had less symptom improvement and a lower probability of remission during 12 weeks of escitalopram treatment. This supports the intervention-efficacy portion of the citation, but the study does not establish that lingering dysfunction impairs functional outcomes in people with treatment-resistant depression. The sentence cites other papers, not Alexopoulos et al. (2015), for relapse. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Gonda et al., 2015 sourcePartly supported

  The Conclusions say cognitive deficits in major depression affect therapeutic response, relapse risk, and functioning, and may persist during remission. The review sections on illness course and pharmacotherapy also link cognitive impairment to poorer functioning and worse SSRI response. These passages do not establish the claim specifically for people with treatment-resistant depression (TRD). (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites Story et al., 2008 sourcePartly supported

  The Discussion (page not provided) reports that depressed older adults with poorer baseline verbal memory and processing speed had less treatment response over one year. It does not establish that lingering dysfunction causes reduced intervention efficacy in people with treatment-resistant depression or measure functional outcomes. The sentence cites other sources, not Story et al., for the separate relapse claim. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Neurocognitive dysfunction is a core depressive symptom for which few effective treatments exist.

“Neurocognitive dysfunction is a core depressive symptom for which few effective treatments exist (Porter et al., 2003;Salagre et al., 2017;Zakzanis et al., 1999).”

• cites Porter et al., 2003 sourcePartly supported

  The Discussion reports significant neurocognitive impairment in young adult out-patients with unipolar depression, supporting the link between depression and cognitive dysfunction. The paper does not establish that it is a core depressive symptom or assess whether few effective treatments exist. The supplied passages have no page numbers. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Salagre et al., 2017 sourceNot checked — no full text of the source
• cites Zakzanis et al., 1999Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Cole et al. (2020) and Cole et al. (2022) used the D-KEFS TMT and Color-Word Interference subtests and found differing results.

“Cole et al., 2020;Cole et al., 2022 used the D-KEFS TMT and Color-Word Interference subtests and found differing results.”

• cites Cole et al., 2020 sourceNot checked — no full text of the source
• cites Cole et al., 2022 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

High frequency (50 Hz) left DLPFC iTBS was administered in all included studies.

“High frequency (50 Hz) Left DLPFC iTBS was administered in all studies.”

May combine two claims.

Such improvement was modest, short-term, and unreplicated.

“However, such improvement was modest, short-term, and unreplicated.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Most included studies (n = 7) included one or more measures of executive function.

“Most studies (n = 7) included one or more measures of executive function.”

May combine two claims.

The small number of articles, mixed study designs, varied statistical analyses, heterogeneity of neurocognitive domains and measures examined, and small sample sizes with restricted demographic factors rendered meta-analysis difficult and clinically unmeaningful.

“In addition, the small number of articles, mixed study designs, varied statistical analyses, heterogeneity of neurocognitive domains and measures examined, and small sample sizes with restricted demographic factors rendered meta-analysis difficult and clinically unmeaningful.”

The quote only partly states this claim.

Scho et al. (2019) reported a slight decline in performance after TBS on Trail Making Test Part A.

“Scho et al. (2019)reported a slight decline in performance after TBS.”

• cites Scho et al., 2019 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In all included studies, TBS was administered at least once weekly (range: 10-100 total sessions).

“In all studies, TBS was administered at least once weekly (range: 10-100 total sessions).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Using the search criteria, 520 references were identified; after removal of reviews, books, book chapters, and duplicates, 102 references remained for title and abstract review.

“Using the search criteria, 520 references were identified.Following the removal of reviews, books, book chapters, and duplicates, 102 references remained for review of the title and abstract.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Other measured neurocognitive domains included attention, learning and memory, and processing speed.

“Other measured neurocognitive domains included attention, learning and memory, and processing speed.”

May combine two claims.

Neither Cristancho et al. (2020) nor Cristancho et al. (2023) found significant results related to the DCCS.

“Neither study found significant results related to the DCCS”

• cites Cristancho et al., 2020 sourceNot checked — no full text of the source
• cites Cristancho et al., 2023 sourceNot checked — no full text of the source

May combine two claims.

No other groups (cTBS, iTBS and cTBS, sham TBS) experienced significant change in performance from baseline to post-treatment on the WCST regardless of response, despite large reductions in depression severity between baseline and post-treatment for responders in the active groups (cTBS: -22.5%; iTBS and cTBS: -52.5%).

“In addition, no other groups (cTBS, iTBS and cTBS, sham TBS) experienced significant change in performance from baseline to post-treatment on the WCST regardless of response, despite large reductions in depression severity between baseline and post-treatment for responders in the active groups (cTBS: -22.5 %; iTBS and cTBS: -52.5 %).”

• cites Cheng et al., 2016 sourceNot checked — no full text of the source

May combine two claims.

Each neurocognitive measure provided only one outcome variable that conflated distinct cognitive functions, making it difficult to delineate which specific functions were affected by TBS.

“Further, as each neurocognitive measure provided only one outcome variable that conflated distinct cognitive functions (e.g., psychomotor speed, visual scanning), it was difficult to delineate which specific functions were affected by TBS.”

May combine two claims.

None of the included studies provided evidence of an improvement in neurocognition after sham stimulation, which suggested that outcomes were not inflated due to practice effects.

“Notably, none of the included studies provided evidence of an improvement in neurocognition after sham stimulation, which suggested that outcomes were not inflated due to practice effects.”

Probably not a substantial claim: may not pass S3 (load-bearing).

DeMayo et al. (2023) reported that subjective cognition improved after treatment.

“In their double-blind randomized placebocontrolled trial of combined D-Cycloserine and iTBS, DeMayo et al. (2023) reported that subjective cognition improved after treatment.”

• cites DeMayo et al., 2023 sourceNot checked — no full text of the source

May combine two claims.

Included studies used various TBS protocols, had differing inclusion and exclusion criteria, and inconsistently defined TRD.

“Included studies also used various TBS protocols, had differing inclusion and exclusion criteria, and inconsistently defined TRD.”

May combine two claims.

While neurocognition may improve during remission, it may not return to premorbid levels.

“While neurocognition may improve during remission, it may not return to premorbid levels (Semkovska, 2021).”

• cites Semkovska, 2021 sourceNot checked — no full text of the source

May combine two claims.

TBS may be a neurocognitively safe antidepressant treatment with potential neurocognitive enhancing effects.

“Nonetheless, the available evidence suggested that TBS may be a neurocognitively safe antidepressant treatment with potential neurocognitive enhancing effects.”

• AssumptionRests on an assumption: The included studies are representative of the available evidence on the neurocognitive effects of TBS for TRD.
• AssumptionRests on an assumption: The standardized neuropsychological tests used in the included studies validly measure the neurocognitive domains they are labeled as measuring.

May combine two claims.

rTMS is considered cognitively safe with mixed evidence regarding its potential for cognitive enhancing properties.

“Importantly, rTMS is considered cognitively safe with mixed evidence regarding its potential for cognitive enhancing properties (Gregory et al., 2022;Kavanaugh et al., 2018;Martin et al., 2017;Schulze-Rauschenbach et al., 2005;Serafini et al., 2015;Wall et al., 2013;Yildiz et al., 2023).”

• cites Gregory et al., 2022 sourceNot checked — no full text of the source
• cites Kavanaugh et al., 2018 sourceNot checked — no full text of the source
• cites Martin et al., 2017 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

TMS is a noninvasive neuromodulation technique that works by creating a brief and strong localized pulsed magnetic field over the surface of the head that induces electrical currents in targeted brain regions.

“TMS is a noninvasive neuromodulation technique that works by creating a brief and strong localized pulsed magnetic field over the surface of the head that induces electrical currents in targeted brain regions (George et al., 1999).”

• cites George et al., 1999 sourceNot checked — no full text of the source

May combine two claims.

SSRIs and SNRIs have mixed evidence regarding their neurocognitive effects with most demonstrating cognitive safety; although some studies demonstrate neurocognitive enhancement, performance tends to remain below performance levels of healthy controls and remission remains unachieved for most participants.

“The newest classes of antidepressants with primarily serotonergic effects, such as selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SNRIs), have mixed evidence regarding their neurocognitive effects with most demonstrating cognitive safety.Although some studies demonstrate neurocognitive enhancement, performance tends to remain below”

• cites Castellano et al., 2016 sourceNot checked — no full text of the source
• cites Herrera-Guzmán et al., 2010 sourceNot checked — no full text of the source
• cites L. Liu et al., 2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

The neurocognitive effects of TBS are less well understood than its antidepressant effects, and there is limited research regarding its neurocognitive effects in the treatment of TRD.

“however, the neurocognitive effects of TBS are less well understood.”

• Also stated in: § 1. Background · plain

  “While there has been evidence published regarding the clinical effects of TBS, there is limited research regarding its neurocognitive effects in the treatment of TRD.”

May combine two claims.

Theta burst stimulation (TBS), a variant of rTMS, has been cleared for the same indication as rTMS and is becoming more widely used in clinical practice because it is a relatively more accessible form of neuromodulation for treatment-resistant depression (TRD).

“Since then, theta burst stimulation (TBS), a variant of rTMS, has been cleared for the same indication and is becoming more widely used in clinical practice given that it is a relatively more accessible form of neuromodulation for treatment-resistant depression (TRD).”

• Also stated in: § 1. Background · plain

  “iTBS for treatment of TRD in adults was cleared by the FDA in 2018, and a relatively newer accelerated protocol called Stanford Neuromodulation Therapy (SNT, formerly SAINT) was cleared by the FDA in 2022 (Tarr, 2022).”

• cites Tarr, 2022Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In the first study of TBS of the human cortex, Huang et al. (2005) introduced continuous (cTBS) and intermittent (iTBS) protocols; cTBS was found to suppress whereas iTBS was found to facilitate cortical excitability.

“In the first study of TBS of the human cortex, Huang et al. (2005) introduced two protocols, those being continuous (cTBS) and intermittent (iTBS).The former was found to suppress whereas the latter was found to facilitate cortical excitability.”

• cites Huang et al., 2005 sourceNot checked — no full text of the source

May combine two claims.

Few treatments exist to address neurocognitive impairment in TRD or cognitive dysfunction in MDD.

“few treatments exist to address neurocognitive impairment in TRD”

• Also stated in: § 1. Background · plain

  “Given that few treatments for cognitive dysfunction in MDD exist (Salagre et al., 2017)”

• cites Salagre et al., 2017 sourceNot checked — no full text of the source

May combine two claims.

The TBS stimulation paradigm mimics endogenous patterns of neural firing associated with induction of LTP and may modulate networks involved in the pathophysiology of depression.

“This stimulation paradigm mimics endogenous patterns of neural firing associated with induction of LTP (Larson and Lynch, 1986;Suppa et al., 2016) and may modulate networks involved in the pathophysiology of depression (Li et al., 2018).”

• cites Larson and Lynch, 1986 sourceNot checked — no full text of the source
• cites Suppa et al., 2016 sourceNot checked — no full text of the source
• cites Li et al., 2018Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Left dorsolateral prefrontal cortex (DLPFC) hypoactivity and right DLPFC hyperactivity have been noted in individuals with MDD.

“Left dorsolateral prefrontal cortex (DLPFC) hypoactivity and right DLPFC hyperactivity has been noted in individuals with MDD (Grimm et al., 2008;Mayberg et al., 2000).”

• cites Grimm et al., 2008 sourceNot checked — no full text of the source
• cites Mayberg et al., 2000 sourceNot checked — no full text of the source

May combine two claims.

High-frequency rTMS tends to increase cortical excitability when applied over the left DLPFC, and low-frequency rTMS tends to decrease cortical activity when applied over the right DLPFC.

“Consequently, the most common parameters for depression treatment are high-frequency rTMS, which tends to increase cortical excitability, applied over the left DLPFC and low-frequency rTMS, which tends to decrease cortical activity, applied over right DLPFC (McClintock et al., 2017).”

• cites McClintock et al., 2017Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Long lasting neuronal effects of rTMS may be due to synaptic changes such as long-term potentiation (LTP) among cortical neurons.

“Long lasting neuronal effects of rTMS may be due to synaptic changes (e.g., long-term potentiation [LTP] among cortical neurons; Ridding & Rothwell, 2007).”

• cites Ridding & Rothwell, 2007 sourceNot checked — no full text of the source

May combine two claims.

Evidence has suggested that TMS may improve psychomotor speed, visual scanning, and set-shifting ability among individuals with TRD.

“For example, evidence has suggested that TMS may improve psychomotor speed, visual scanning, and set-shifting ability among individuals with TRD (Martin et al., 2017).”

• cites Martin et al., 2017 sourceNot checked — no full text of the source

May combine two claims.

TBS may improve verbal learning and memory, but evidence is mixed.

“Taken together, these results suggest that TBS may improve verbal learning and memory; however, evidence is mixed.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Whether those medications improve neurocognitive function to a greater degree than expected from improvement in depressive symptomology is unclear.

“Whether those medications improve neurocognitive function to a greater degree than expected from improvement in depressive symptomology is unclear (Biringer et al., 2009).”

• cites Biringer et al., 2009 sourceNot checked — no full text of the source

May combine two claims.

A small number of studies met criteria for inclusion, which limits firm conclusions.

“Given the dearth of evidence on neurocognitive effects of TBS in TRD, a small number of studies met criteria for inclusion which limits firm conclusions.”

May combine two claims.

Neurocognitive performance remained relatively stable across timepoints and/or was similar across timepoints between conditions.

“suggesting that neurocognitive performance remained relatively stable across timepoints and/or was similar across timepoints between conditions (e.g., active TBS, active rTMS, sham).”

May combine two claims.

The results of the current systematic review provide evidence in support of neurocognitive safety and potential benefit of TBS intervention for TRD when administered to the dorsolateral prefrontal cortex.

“The results of the current systematic review provide evidence in support of neurocognitive safety and potential benefit of theta burst stimulation intervention for TRD when administered to the dorsolateral prefrontal cortex.”

May combine two claims.

Those findings of possible cognitive improvement need to be interpreted with caution given the magnitude of those enhancements was unknown and there were mixed findings without replication for each cognitive domain.

“However, those findings of possible cognitive improvement need to be interpreted with caution given the magnitude of those enhancements was unknown and there were mixed findings without replication for each cognitive domain.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The potential effect of TBS on 1-back task performance may have been indicative of a change in processing speed rather than working memory per se given the improvement in reaction time rather than accuracy.

“This may have been indicative of a change in processing speed rather than working memory per se given the improvement in reaction time rather than accuracy.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Previous reviews have suggested that standard rTMS for TRD may produce modest cognitive enhancing effects.

“Of note, previous reviews (Martin et al., 2017;Serafini et al., 2015) have suggested that standard rTMS for TRD may produce modest cognitive enhancing effects”

• cites Martin et al., 2017 sourceNot checked — no full text of the source
• cites Serafini et al., 2015 sourceNot checked — no full text of the source

May combine two claims.

Taken together, the results suggest that TBS may not enhance processing speed, although evidence is mixed.

“Taken together, these results suggest that TBS may not enhance processing speed, although evidence is mixed.”

• AssumptionRests on an assumption: The included studies are representative of the available evidence on the neurocognitive effects of TBS for TRD.
• AssumptionRests on an assumption: The standardized neuropsychological tests used in the included studies validly measure the neurocognitive domains they are labeled as measuring.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Some evidence suggests sertraline and bupropion have superior neurocognitive enhancing effects compared to other serotonergic agents, and paroxetine is typically associated with worse neurocognitive outcomes.

“Some evidence suggests that sertraline and bupropion have superior neurocognitive enhancing effects compared to other serotonergic agents (Baune and Renger, 2014;Biringer et al., 2009) and that the use of paroxetine is typically associated with worse neurocognitive outcomes (Biringer et al., 2009).”

• cites Baune and Renger, 2014 sourceNot checked — no full text of the source
• cites Biringer et al., 2009 sourceNot checked — no full text of the source

May combine two claims.

TBS may improve executive function, although evidence is mixed.

“Taken together, these results suggest that TBS may improve executive function although evidence is mixed.”

May combine two claims.

While a flourishing area of research has demonstrated the efficacy of TBS for improving mood symptoms in TRD, to date, relatively little evidence exists regarding its neurocognitive effects.

“While a flourishing area of research has demonstrated the efficacy of TBS for improving mood symptoms in TRD, to date, relatively little evidence exists regarding its neurocognitive effects.”

Classified as probably not a substantial claim. May combine two claims.

Initial findings are promising, but more research is necessary to adequately inform the neurocognitive effects of TBS in TRD.

“Initial findings are promising, but more research is necessary to adequately inform the neurocognitive effects of TBS in TRD.”

• AssumptionRests on an assumption: Most clinical studies focus solely on mood symptoms despite prognosis being predicted by neurocognitive dysfunction.

May combine two claims.

Individual study results must be interpreted with caution because many lacked a sham control group, included mixed samples, and were open-label or used only a randomized single-blind design that lacked control for placebo effects.

“Regarding individual study results, they must be interpreted with caution given that many lacked a sham control group, included mixed samples (both unipolar and bipolar depression), and were open-label or used only a randomized single-blind study design that lacked control for potential placebo effects.”