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Transcranial magnetic stimulation (TMS) is being studied for substance use disorders using a slight variation on the stimulus technique used for the treatment of major depression. Would you have thought that this could be extended to cigarette smoking?
Hi! Jim Phelps here for the Psychopharmacology Institute. TMS for substance use is a new field. A 2019 consensus statement from 75 researchers in the field reminds us “as with any emerging field, enthusiasm must be tempered by reason.” I like the sound of that. Not having been watching the TMS for substance use research, I was surprised to find that an Israeli team tried TMS for smoking cessation back in 2014, and it was more effective than a control treatment.
That study and a further pilot study led to a larger randomized trial now being reported by Abraham Zangen and a large multicentric team. Picture their participants: Fifty-fifty males and females. On average, they are 45 years old and started smoking at age 17. Seventy-five percent of them have tried to quit 3 or more times. On a 1 to 10 scale of desire to quit, they’re at a 9. They’re randomized, and they begin active or sham treatment. A magnetic card inserted by the participant determines which coil—active or dummy—was activated. Same helmet, same noise, same scalp sensations for both groups. A very solid blinding process. Treatments were once daily for 3 weeks and then once weekly for 3 weeks at 10 Hz. This is the same frequency used for major depression but targeting deeper into the lateral prefrontal and insular cortices.
Self-report of cigarettes was used, but it was confirmed by urine cotinine levels. The principal outcome was continuous quitting, which is abstinence assessed after 6 weeks of treatment and then again by telephone questionnaire at 18 weeks. The sample size was big at 262 participants, although one-quarter of the participants dropped out before completing the daily sessions. These dropout rates were the same for treatment and sham TMS. If you look just at the participants who made it through the 3 weeks of daily sessions, the completer analysis, 25% of the active group were still abstinent at 6 weeks vs 6% of the sham group. That’s a number needed to treat (NNT) of 5, and that’s the rosiest way to look at the outcomes here. The harshest view would be the 18-week abstinence rate for all comers which was 19% vs 9%. That’s an NNT of 10.
Now, for comparison purposes, let’s compare varenicline. A meta-analysis found abstinence rates of 48% at 9 to 12 weeks vs 15% in the placebo group. That’s an NNT of 3. A Cochrane meta-analysis found bupropion less effective than varenicline and about the same as nicotine replacement therapy. Dr. Zangen and colleagues point out that most of the older studies used saliva carbon monoxide, not urinary cotinine, to confirm self-report, so they measured hours of abstinence, not days. But, overall, for very rough comparison purposes, we’re looking at an NNT of 3 at 9 to 12 weeks for varenicline vs an NNT of 5 for successfully completed TMS and an NNT of 10 for TMS if you count all the participants using their rigorous urinary cotinine test at 18 weeks.
As for the adverse effects of TMS in this study, the most frequent adverse event was headache in both the active and sham groups, 24% and 18%, respectively. Interestingly, despite some head and neck pain during treatments, the blind was intact. The majority of subjects in each group didn’t know which treatment they had received.
In summary, we have here a randomized trial of TMS for smoking cessation in which active treatment is clearly superior to sham treatment both in the short and longer term. It doesn’t beat varenicline, but it does potentially add one more option for people who are really struggling to quit.
For more on this, digging into that Cochrane meta-analysis of bupropion studies, which is linked here at the Psychopharmacology Institute, could teach you more about its effects for smokers.
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 smoking cessation for adults.
Keywords: Smoking cessation; addiction medicine; cigarette consumption; cigarette craving; insula; lateral prefrontal cortex; repetitive transcranial magnetic stimulation.
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Reference
Zangen, A., Moshe, H., Martinez, D., Barnea‐Ygael, N., Vapnik, T., Bystritsky, A., … & George, M. S. (2021). Repetitive transcranial magnetic stimulation for smoking cessation: a pivotal multicenter double‐blind randomized controlled trial. World Psychiatry, 20(3), 397-404.
Related References
Howes, S., Hartmann‐Boyce, J., Livingstone‐Banks, J., Hong, B., & Lindson, N. (2020). Antidepressants for smoking cessation. Cochrane Database of Systematic Reviews, 4.
