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Can Low-Frequency Repetitive Transcranial Magnetic Stimulation Really Relieve Medication-Resistant Auditory Verbal Hallucinations? Negative Results from a Large Randomized Controlled Trial
Abstract
Background Several studies have applied low-frequency repetitive transcranial magnetic stimulation (rTMS) directed at the left temporoparietal area (TP) for the treatment of auditory verbal hallucinations (AVH), but findings on efficacy are inconsistent. Furthermore, recent functional magnetic resonance imaging (fMRI) studies indicate that the left TP is not a general focus of activation during the experience of AVH. The aims of this study are twofold: to investigate the effects of rTMS on AVH in a double blind, randomized, sham-controlled study; and to investigate whether the efficacy can be improved when rTMS is guided by individual fMRI scans of hallucinatory activation.Methods Sixty-two patients with medication-resistant AVH were randomized over three conditions: rTMS targeted at the area of maximal hallucinatory activation calculated from individual fMRI scans during AVH, rTMS directed at the left TP, and sham treatment. Repetitive TMS was applied during 15 sessions of 20 min each, at 1 Hz and 90% of the individual motor threshold. The severity of AVH and other psychotic symptoms were monitored during treatment and 3-month follow-up, with the Auditory Hallucination Rating Scale, the Positive and Negative Syndrome Scale, and the Psychotic Symptom Rating Scales.Results The effects of fMRI-guided rTMS and left TP rTMS on the severity of AVH were comparable to those of sham treatment. No differences in severity of general psychotic symptoms were found among the three treatment conditions.Conclusions Low-frequency rTMS administered to the left TP or to the site of maximal hallucinatory activation is not more effective for medication-resistant AVH than sham treatment.
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“Notably, a relatively large randomized controlled trial (N = 62) failed to find any significant advantage of active rTMS over sham stimulation”
From Auditory verbal hallucinations as atypical inner speech monitoring, and the potential of neurostimulation as a treatment option (2013) · cites this paper as Slotema et al., 2011
In the citing paper
“Of the three studies discussed here that have achieved adequate power, one finds no effect of neurostimulation (Slotema et al., 2011), and the other two originate from the same institution (Hoffman et al., 2005, 2013).”
From Auditory verbal hallucinations as atypical inner speech monitoring, and the potential of neurostimulation as a treatment option (2013) · cites this paper as Slotema et al., 2011
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“However, another randomized sham-controlled trial by Slotema and colleagues (2011)([5]) did not find any benefit of rTMS treatment and did not find any advantage in using individualized sites for rTMS stimulation guided by fMRI.”
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“The use of individual fMRI scans to determine the location of hubs during hallucinatory activity may improve efficacy, although an RCT of our group failed to show a significant advantage of fMRI guidance (Slotema et al., 2011).”
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“Such trials are not possible with ECT or VNS, but have been done with TMS, underscoring both the clinical and research utility of that mode of neuromodulation (Slotema et al. 2011).”
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“Research by Slotema et al. suggests that low-frequency (1 Hz) rTMS may not be an effective treatment strategy (30), and a systematic review indicates that current evidence is insuf fi cient to support the notion that rTMS provides additional bene fi ts when used as an adjunct to antipsychotic…”
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Metadata
- Authors
- Slotema, C. W., Blom, J. D., de Weijer, A. D., Diederen, K. M., Goekoop, R., Looijestijn, J., Daalman, K., Rijkaart, A.-M., Kahn, R. S., Hoek, H. W., & Sommer, I. E. C.
- Affiliations
- Parnassia Groep (NL)
- University Medical Center Utrecht (NL)
- University Medical Center Groningen (NL)
- Corresponding author
- Slotema, Christina W.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 69
- Issue
- 5
- Pages
- 450-456
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2098660547
- Cited by
- 137
- References
- 42
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 7 · 2019: 3 · 2018: 5 · 2017: 9 · 2016: 11 · 2015: 8 · 2014: 13 · 2013: 15 · 2012: 22
- FWCI
- 9.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- NWO ZonMW (Dutch Scientific Research Foundation-Dutch National Institute of Health Research
- Stichting tot Steun (Dutch Support Foundation
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
- Keywords
- auditory verbal hallucinations, low-frequency repetitive transcranial magnetic stimulation, left temporoparietal cortex, sham-controlled treatment, treatment efficacy, psychotic symptoms
- MeSH terms
- Adult, Brain, Data Interpretation, Statistical, Double-Blind Method, Drug Resistance, Female, Hallucinations, Humans, Magnetic Resonance Imaging, Male, Psychiatric Status Rating Scales, Psychotic Disorders, Schizophrenia, Schizophrenic Psychology, Antipsychotic Agents, Treatment Outcome, Transcranial Magnetic Stimulation
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