Repetitive transcranial magnetic stimulation for smoking cessation: a pivotal multicenter double-blind randomized controlled trial

Abraham Zangen, Hagar Moshe, Diana Martinez, Noam Barnea-Ygael, Tanya Vapnik, Alexander Bystritsky, Walter Duffy, Doron Toder, Leah Casuto, Moran Lipkinsky Grosz, Edward V. Nunes, Herbert Ward, Aron Tendler, David Feifel, Oscar Morales, Yiftach Roth, Dan V Iosifescu, Jaron Winston, Theodore Wirecki, Ahava SteinFrederic Deutsch, Xingbao Li, Mark S. George

Research output: Contribution to journalArticlepeer-review


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 (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 (X2=5.655, p=0.017). Among completers (N=169), the CQR until Week 18 was 28.0% and 11.7%, respectively (X2=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.

Original languageAmerican English
Pages (from-to)397-404
Number of pages8
JournalWorld Psychiatry
Issue number3
StatePublished - 1 Oct 2021


  • Smoking cessation
  • addiction medicine
  • cigarette consumption
  • cigarette craving
  • insula
  • lateral prefrontal cortex
  • repetitive transcranial magnetic stimulation

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Phychiatric Mental Health


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