ABSTRACT
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 bilat-eral 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 (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 smok-ing cessation for adults.
ABSTRACT
BACKGROUND: Prefrontal Transcranial Magnetic Stimulation (TMS) therapy repeated daily over 4-6 weeks (20-30 sessions) is US Food and Drug Administration (FDA) approved for treating Major Depressive Disorder in adults who have not responded to prior antidepressant medications. In 2011, leading TMS clinical providers and researchers created the Clinical TMS Society (cTMSs) (www.clinicaltmssociety.org, Greenwich, CT, USA), incorporated in 2013. METHODS: This consensus review was written by cTMSs leaders, informed by membership polls, and approved by the governing board. It summarizes current evidence for the safety and efficacy of the use of TMS therapy for treating depression in routine clinical practice. Authors systematically reviewed the published TMS antidepressant therapy clinical trials. Studies were then assessed and graded on their strength of evidence using the Levels of Evidence framework published by the University of Oxford Centre for Evidence Based Medicine. The authors then summarize essentials for using TMS therapy in routine clinical practice settings derived from discussions and polls of cTMSs members. Finally, each summary clinical recommendation is presented with the substantiating peer-reviewed, published evidence supporting that recommendation. When the current published clinical trial evidence was insufficient or incomplete, expert opinion was included when sufficient consensus was available from experienced clinician users among the membership of the cTMSs, who were polled at the Annual Meetings in 2014 and 2015. CONCLUSIONS: Daily left prefrontal TMS has substantial evidence of efficacy and safety for treating the acute phase of depression in patients who are treatment resistant or intolerant. Following the clinical recommendations in this document should result in continued safe and effective use of this exciting new treatment modality.
