Transcranial Magnetic Stimulation for Smoking Cessation

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation method that is increasingly used to treat psychiatric disorders, primarily depression. Initial studies suggest that rTMS may help treat addictions, but evaluation is required in a multicenter randomized controlled trial (RCT). METHODS: Here, we tested in chronic smokers whether repeated bilateral rTMS of the lateral prefrontal and insular cortices reduces cigarette craving and consumption and increases quit rates. This multicenter RCT included 14 sites and 262 chronic smokers who received Active or Sham rTMS. Participants received three weeks of daily rTMS sessions following cue-induced craving and were monitored up to four months. The primary outcome was the four-week continuous quit rate (CQR) measured by daily smoking diaries and verified by urine cotinine measures. Secondary outcome measures included changes in cigarette consumption and craving. This trail is registered at ClinicalTrials.gov, number NCT02126124. RESULTS: In the intent to treat analysis set, CQR was 19·4% following Active and 8·7% following Sham rTMS (χ 2 = 5·655, p=0·017). Among completers (N=169), CQR was 28·0% and 11·7%, respectively (χ 2 = 7·219, p=0·007). CQR within the first six weeks was 25·3% (Active) and 6·4% (Sham) (χ 2 = 11·885, p=0·0006), of which 63% (Active) and 50% (Sham) remained abstinent for at least four months (χ 2 =8·46, p=0·003). Significant between-group differences in cigarette consumption and craving emerged as early as two weeks into treatment. CONCLUSIONS: This study establishes a safe treatment protocol that promotes smoking cessation by stimulating the relevant brain circuits. It represents the first large multicenter RCT of brain stimulation for addiction medicine. Funded by: BrainsWay Declaration of Interest: Oscar Morales occasional reports consult work for Brainsway; Dr. Tendler reports personal fees from Brainsway, other from Advanced Mental Health Care Inc./DTMS Center LLC, outside the submitted work; Dr. Roth reports personal fees from Brainsway, outside the submitted work; In addition, Dr. Roth has a patent US 7,407,478 with royalties paid; Mr. Deutsch reports personal fees from Brainsway, during the conduct of the study; personal fees from Brainsway, outside the submitted work; David Feifel reports he is a member of Brainsway's Scientific Advisory Board (non-compensated); Dr. Duffy reports other from Brainsway, during the conduct of the study; other from Alivation Health LLC and Alivation Research LLC, outside the submitted work; Prof. Abraham Zangen is an inventor of Deep TMS coils which were patented by the NIH and other academic institutions where Abraham Zangen worked. These patents were licensed to BrainsWay and Abraham Zangen receives royalties from these patents. In addition Prof. Zangen serves as consultant for BrainsWay and has finanacial insterests in BrainsWay; Dr. Todder reports other from BRAINSWAY, during the conduct of the study; all other authors have nothing to disclose. Ethical Approval:The trial protocol (Supplementary Materials; SM 1.1) was approved by local institutional review boards and was registered at clinicaltrials.gov (NCT02126124). The study was conducted in the United States (12 sites) and Israel (two sites), with active enrollment from August 2014 through August 2019. The trial was supported by industry (BrainsWay).