Comparison of clinical outcomes with left unilateral and sequential bilateral transcranial magnetic stimulation (TMS) treatment of major depressive disorder in a large patient registry
Open accessAbstract
BACKGROUND: It has been suggested that sequential bilateral (SBL) TMS, combining high frequency, left dorsolateral prefrontal cortex (DLPFC) stimulation and low frequency, right DLPFC stimulation, is more effective than unilateral TMS. OBJECTIVE: To contrast treatment outcomes of left unilateral (LUL) and SBL protocols. METHODS: Registry data were collected at 111 practice sites. Of 10,099 patients, 3,871 comprised a modified intent-to-treat (mITT) sample, defined as a primary MDD diagnosis, age ≥18, and PHQ-9 completion before TMS and at least one PHQ-9 assessment after baseline. The mITT sample received high frequency (10 Hz) LUL TMS exclusively (N = 3,327) or SBL TMS in at least 90% of sessions (N = 544). Completers (N = 3,049) were responders or had received ≥20 sessions and had an end of acute treatment PHQ-9 assessment. To control for site effects, a Matched sample (N = 653) included Completers at sites that used both protocols. To control for selection bias, the SBL group was also compared to a Restricted LUL group, drawn from sites where no patient switched to SBL after substantial exposure to LUL TMS. Secondary analyses were conducted on CGI-S ratings. RESULTS: The LUL group had superior outcomes compared to the SBL group for multiple PHQ-9 and CGI-S continuous and categorical measures in the mITT, Completer and Matched samples, including in the specified primary analyses. However, outcome differences were not observed when comparing the Restricted LUL and SBL groups. Within SBL protocols, the LUL-RUL order had superior outcomes compared to the RUL-LUL order in all CGI-S, but not PHQ-9, measures. CONCLUSIONS: While limited by the naturalistic design, there was no evidence that SBL TMS was superior to LUL TMS. The sequential order of RUL TMS followed by LUL TMS may have reduced efficacy compared to LUL TMS followed by RUL TMS.
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Recent clinical registry data indicate no added benefit for bilateral over unilateral stimulation in a lifespan sample.
“However, recent clinical registry data indicate no added benefit for bilateral over unilateral stimulation in a lifespan sample.37”
From Effectiveness of Standard Sequential Bilateral Repetitive Transcranial Magnetic Stimulation vs Bilateral Theta Burst Stimulation in Older Adults With Depression (2022) · cites this paper as [37]
The Discussion reports that this registry study found no evidence that sequential bilateral TMS was superior to left unilateral TMS. The Methods define the analyzed sample as adults aged 18 or older, so the source does not establish the result across the full lifespan. (LLM, conf=0.78)
Experimental — accuracy not yet measuredThe decision to compare TBS with standard bilateral TMS rather than sham was based on network meta-analytic findings supporting bilateral standard TMS over sham treatment and the widespread use of bilateral standard TMS in the community setting.
“The decision to compare TBS with standard bilateral TMS rather than sham was a recognition of network meta-analytic findings supporting bilateral standard TMS over sham treatment34,35 as well as the widespread use of bilateral standard TMS in the community setting.37”
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- Authors
- Aaronson, S. T., Carpenter, L. L., Hutton, T. M., Kraus, S., Mina, M., Pages, K., Shi, L., West, W. S., & Sackeim, H. A.
- Affiliations
- University of Maryland, Baltimore (US)
- Brown University (US)
- Neuronetics (United States) (US)
- Augusta University (US)
- Corresponding author
- Aaronson, Scott T.
- ORCID
- Venue
- Brain Stimulation
- Publisher
- Elsevier BV
- Published
- 2022-03
- Volume
- 15
- Issue
- 2
- Pages
- 326-336
- ISSN
- 1876-4754 (ISSN-L)
- 1935-861X
- OpenAlex
- W4206921358
- Cited by
- 50
- References
- 56
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 15 · 2023: 9 · 2022: 3
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Brain stimulation (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Keywords
- transcranial magnetic stimulation, major depressive disorder, dorsolateral prefrontal cortex, high-frequency stimulation, low-frequency stimulation, treatment order, PHQ-9, Clinical Global Improvement, treatment response, patient registry
- MeSH terms
- Dorsolateral Prefrontal Cortex, Major Depressive Disorder, Depressive Disorder, Major, Humans, Registries, Treatment Outcome, Prefrontal Cortex, Transcranial Magnetic Stimulation
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