Repetitive transcranial magnetic stimulation for smoking cessation: a pivotal multicenter double‐blind randomized controlled trial
Open accessAbstract
Repetitive transcranial magnetic stimulation (rTMS) is a non‐invasive brain stimulation method increasingly used to treat psychiatric disorders, primarily depression. Initial studies suggest that rTMS may help to treat addictions, but evaluation in multicenter randomized controlled trials (RCTs) is needed. We conducted a multicenter double‐blind RCT in 262 chronic smokers meeting DSM‐5 criteria for tobacco use disorder, who had made at least one prior failed attempt to quit, with 68% having made at least three failed attempts. They received three weeks of daily bilateral active or sham rTMS to the lateral prefrontal and insular cortices, followed by once weekly rTMS for three weeks. Each rTMS session was administered following a cue‐induced craving procedure, and participants were monitored for a total of six weeks. Those in abstinence were monitored for additional 12 weeks. The primary outcome measure was the four‐week continuous quit rate (CQR) until Week 18 in the intent‐to‐treat efficacy set, as determined by daily smoking diaries and verified by urine cotinine measures. The trial was registered at ClinicalTrials.gov (NCT02126124). In the intent‐to‐treat analysis set (N=234), the CQR until Week 18 was 19.4% following active and 8.7% following sham rTMS (X 2 =5.655, p=0.017). Among completers (N=169), the CQR until Week 18 was 28.0% and 11.7%, respectively (X 2 =7.219, p=0.007). The reduction in cigarette consumption and craving was significantly greater in the active than the sham group as early as two weeks into treatment. This study establishes a safe treatment protocol that promotes smoking cessation by stimulating relevant brain circuits. It represents the first large multicenter RCT of brain stimulation in addiction medicine, and has led to the first clearance by the US Food and Drug Administration for rTMS as an aid in smoking cessation for adults.
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At present, the only FDA-approved SUD-related indications for neuromodulation are transcranial magnetic stimulation for smoking cessation, and percutaneous nerve field stimulation for treatment of opioid withdrawal.
“At present, the only FDA- approved SUD- related indications for neuromodulation are transcranial magnetic stimulation for smok ing cessation 216 , and percutaneous nerve field stimulation for treat ment of opioid withdrawal 215 .”
From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [216]
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- Authors
- Zangen, A., Moshe, H., Martinez, D., Barnea‐Ygael, N., Vapnik, T., Bystritsky, A., Duffy, W., Toder, D., Casuto, L., Grosz, M. L., Nunes, E. V., Ward, H., Tendler, A., Feifel, D., Morales, O., Roth, Y., Iosifescu, D. V., Winston, J., Wirecki, T., Stein, A., Deutsch, F., Li, X., & George, M. S.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- Department of Psychiatry Columbia University Irving Medical Center New York NY USA
- CalNeuro Research Group (US)
- Alivation (United States) (US)
- Department of Life Sciences and Zlotowski Centre for Neuroscience Ben‐Gurion University of the Negev Beer‐Sheva Israel
- Lindner Center of HOPE (US)
- Tel Aviv University (IL)
- Columbia University Irving Medical Center (US)
- University of Florida Health (US)
- Advanced Mental Health Care (US)
- Kadima Neuropsychiatry Institute La Jolla CA USA
- Harvard University (US)
- New York University (US)
- Senior Adults Specialty Research Austin TX USA
- TMS Center of Colorado Lakewood CO USA
- A. Stein ‐ Regulatory Affairs Consulting Ltd. Kfar Saba Israel
- Biostatistical Consulting, BioStats Modiin‐Maccabim‐Reut Israel
- Medical University of South Carolina (US)
- ORCID
- Venue
- World Psychiatry
- Publisher
- Wiley
- Published
- 2021-09-09
- Volume
- 20
- Issue
- 3
- Pages
- 397-404
- ISSN
- 1723-8617 (ISSN-L)
- 2051-5545
- PMC
- PMC8429333
- OpenAlex
- W3197696608
- Cited by
- 247
- References
- 41
- Citations by year
- 2026: 39 · 2025: 58 · 2024: 54 · 2023: 64 · 2022: 30 · 2021: 2
- FWCI
- 15.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- World Psychiatry (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- BrainsWay
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- repetitive transcranial magnetic stimulation, smoking cessation, tobacco use disorder, addiction treatment, prefrontal cortex, insula, nicotine craving, sham-controlled treatment, FDA clearance, non-invasive brain stimulation
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