Smoking Cessation Induced by Deep Repetitive Transcranial Magnetic Stimulation of the Prefrontal and Insular Cortices: A Prospective, Randomized Controlled Trial

doi:10.1016/j.biopsych.2014.05.020

Biological Psychiatry

Volume 76, Issue 9, 1 November 2014, Pages 742-749

https://doi.org/10.1016/j.biopsych.2014.05.020 Get rights and content

Background

Tobacco smoking is the leading cause of preventable death in developed countries. Our previous studies in animal models and humans suggest that repeated activation of cue-induced craving networks followed by electromagnetic stimulation of the dorsal prefrontal cortex (PFC) can cause lasting reductions in drug craving and consumption. We hypothesized that disruption of these circuitries by deep transcranial magnetic stimulation (TMS) of the PFC and insula bilaterally can induce smoking cessation.

Methods

Adults (N = 115) who smoke at least 20 cigarettes/day and failed previous treatments were recruited from the general population. Participants were randomized to receive 13 daily sessions of high-frequency, low-frequency or sham stimulation following, or without, presentation of smoking cues. Deep TMS was administered using an H-coil version targeting the lateral PFC and insula bilaterally. Cigarette consumption was evaluated during the treatment by measuring cotinine levels in urine samples and recording participants’ self-reports as a primary outcome variable. Dependence and craving were assessed using standardized questionnaires.

Results

High (but not low) frequency deep TMS treatment significantly reduced cigarette consumption and nicotine dependence. The combination of this treatment with exposure to smoking cues enhanced reduction in cigarette consumption leading to an abstinence rate of 44% at the end of the treatment and an estimated 33% 6 months following the treatment.

Conclusions

This study further implicates the lateral PFC and insula in nicotine addiction and suggests the use of deep high-frequency TMS of these regions following presentation of smoking cues as a promising treatment strategy.

Section snippets

Methods and Materials

This study was a prospective, double-blind, placebo-controlled, randomized clinical trial performed at Beer Yaakov Mental Health Institute, Israel (2010–2013). The study was approved by the local Institutional Review Board and the Israeli Ministry of Health.

Participant Characteristics

Table 2 presents descriptive statistics for each treatment group. No significant differences were observed at baseline among the various treatment groups.

Self-Reported Number of Cigarettes

The number of cigarettes smoked per day, as self-reported by the participants before the first treatment session (on the screening day) and after the last treatment session, is presented in Figure 1A. ANCOVA for the change in these values revealed a significant treatment effect, F_2,76 = 14.56, p < .0001. A greater degree of reduction was found

Discussion

This study examined effects of multiple treatment sessions with deep rTMS over the lateral PFC and insula, using either high- or low-frequency pulses, on cigarette dependence, craving, and consumption.

To the best of our knowledge, this is the first large scale clinical trial of rTMS in the treatment of smoking addiction that demonstrates a decrease in cigarette consumption with an indication for an enduring smoking cessation effect. The current study extends our earlier study showing effect of

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Introduction: A substantial proportion of smokers wishing to quit do not stop smoking when using current therapies to aid cessation. Magnetic pulses to specific brain areas designated as transcranial magnetic stimulation may modulate brain activity and thereby change chemical dependencies. Deep transcranial magnetic stimulation (dTMS) with the H4 coil stimulates neuronal pathways in the lateral prefrontal cortex and insula bilaterally, areas involved in tobacco addiction. Objective: To evaluate the efficacy and safety of dTMS with T4 coil in smoking cessation. Methods: In a double blind, controlled clinical trial, adult smokers of at least 10 cigarettes/day were randomized to active (n = 50) versus sham dTMS (n = 50). The protocol involved up to 21 sessions administered over up to 12 weeks. Tobacco use was monitored by self-report and confirmed by expired air monoximetry (at each dTMS visit) and blood cotinine (at the screening visit and at the end of sessions). Participants completed abstinence, mood and cognition scales at determined timepoints during follow-up. Results: In the intention to-treat-analysis, the cessation rate of the intervention and control groups was 14.0%. The reported side effects were as expected for this procedure. Although there were no serious adverse events, three participants were withdrawn according to safety criteria. Conclusion: Active treatment with dTMS H4 coil was safe but not effective for smoking cessation.
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Archival ReportSmoking Cessation Induced by Deep Repetitive Transcranial Magnetic Stimulation of the Prefrontal and Insular Cortices: A Prospective, Randomized Controlled Trial

Background

Methods

Results

Conclusions

Section snippets

Methods and Materials

Participant Characteristics

Self-Reported Number of Cigarettes

Discussion

Pharmacol Biochem Behav

Brain Res Brain Res Rev

Clin Neurophysiol

Prog Neurobiol

Neurosci Biobehav Rev

Brain Stimul

Alcohol

Neuroimage

Clin Neurophysiol

Clin Neurophysiol

Biol Psychiatry

Schizophr Res

Clin Neurophysiol

Neuropsychopharmacology

Neuroimage

Brain Stimul

Neurosci Biobehav Rev

Curr Opin Neurobiol

Behav Brain Res

Neuron

Drug Alcohol Depend

Brain Res

Behav Brain Res

WHO report on the global tobacco epidemic

Cigarette excise tax structure and cigarette prices: Evidence from the global adult tobacco survey and the U.S. National adult tobacco survey

Nicotine Tob Res

Addiction and the brain: The neurobiology of compulsion and its persistence

Nat Rev Neurosci

Archival Report
Smoking Cessation Induced by Deep Repetitive Transcranial Magnetic Stimulation of the Prefrontal and Insular Cortices: A Prospective, Randomized Controlled Trial