For centuries, the consumption of products containing tobacco has actuated human dependence on the psychoactive chemical nicotine. Tobacco Use Disorder (TUD) is a recognized Substance-Related Disorder commonly diagnosed in individuals who demonstrate daily consumption of cigarettes, smokeless tobacco, hookah, or other tobacco-containing products. Individuals diagnosed with TUD tend to experience explicit symptoms of withdrawal when attempting to terminate tobacco usage (American Psychiatric Association, 2013). Many forms of treatment have been implemented to promote the cessation of tobacco use, with a coalescence of cognitive behavioral therapy and pharmacotherapy generally being the most common avenue of treatment. Within the past decade, however, researchers have begun to explore the efficacy of a new form of treatment to encourage cessation of tobacco smoking, Repetitive Transcranial Magnetic Stimulation (rTMS).
rTMS is a non-invasive procedure for the treatment of psychological, psychiatric, and neurological disorders, which has been in practice since 2008 (Mann and Malhi, 2021; Zangen et al., 2021). rTMS therapy constitutes a large electrically charged coil to be placed around the scalp of a patient. Once activated, the coil produces rapid electrical pulses varying in amplitude, which perpetuate a stable electromagnetic field around a specified region of the brain (Roth et al., 2002). Electrical currents offset by the electromagnetic field penetrate cortical tissue, inducing neuronal depolarization (Zangen et al., 2021) and resulting in protensive neuroplastic transformations when administered consistently (Flint, 2021, p. 153). Previous studies exploring the efficacy of rTMS in treating clinical depression have indicated that rTMS treatment directed to the left dorsolateral prefrontal cortex—a part of the brain which experiences increased activity in patients who are clinically depressed—has been associated with remission of depressive symptoms (Baeken et al., 2019). As forms of TMS therapy have been approved by the U.S. Food and Drug Administration to treat obsessive-compulsive disorder and major depressive disorder, a study conducted by Zangen and colleagues aimed to demonstrate the use of TMS therapy as a possible treatment for smoking cessation.
Zangen and his team employed the use of a double-blind procedural study comprising adults, aged 22 to 70, who suffer from tobacco use disorder and stated intentions to terminate their addiction (Zangen et al., 2021). Participants were randomly assigned into an active group that received rTMS treatment and a sham group that received a placebo treatment. rTMS treatment for the active group was directed to the lateral and insular cortices of the subjects’ brains. During an initial three-week period, both groups were administered rTMS treatment (active or sham) five days a week; groups were also given treatment once a week during an additional three-week follow-up period. Before the administration of each treatment, participants in both groups experienced a five-minute provocation session in which participants were treated with visual and audiovisual stimuli, which were designed to provoke cigarette cravings. After each rTMS session, a motivational speech supporting smoking cessation was read to each participant. The use of a provocation and motivation procedure before and after rTMS treatment by Zangen and his team was influenced by research suggesting that mild provocation before TMS treatment may condition brain areas to be more acquiescent to plastic change (Tendler et al., 2019). Zangen et al., however, did not measure the influence of a provocation procedure on the effectiveness of rTMS therapy, or on the behavior demonstrated by the sham group, potentially confounding results. During the treatment period for the study, the number of cigarettes smoked by each participant was self-reported through a daily diary, and nicotine levels were confirmed by a urine sample which was tested weekly for cotinine levels. The choice to test for cotinine levels reflects an improvement to previous clinical trials in smoking cessation medication which utilized carbon monoxide breath testing, which would only confirm cessation for hours surrounding treatment in contrast to cotinine testing which would be able to confirm abstinence for days. Levels of craving were recorded by Zangen and associates once before and once after each provocation procedure, as well as once after each rTMS administration. After the three-week treatment period and consecutive follow-up, Zangen et al. (2021) discovered that the active group, which received daily rTMS therapy directed at the lateral prefrontal and insular cortices, had been two times more likely to abstain from smoking tobacco products than the sham (placebo) group. Zangen and colleagues also found that the active group who received rTMS treatment was less affected by the pre-treatment provocation procedure in relation to the sham group following the first day of treatment.
Despite the promising results Zangen and his team recorded during the experiment, the study did have its shortcomings. When compared to trials of medicines such as varenicline and bupropion, which are Food and Drug Administration (FDA) approved for smoking cessation, the rTMS study had a relatively small sample size and short follow-up period (Zangen et al., 2021). A larger sample size would allow for the study conducted by Zangen and his team to serve as a more efficacious comparison to other studies of treatment for smoking cessation and would permit participants examined during the follow-up period to best represent the behavior of a population of patients diagnosed with TBD. Zangen and team also do not factor in the degree the provocation and motivation procedure influences cessation and craving in both the active and sham groups. The results collected in the study are confounded by the presence of a provocation and motivation procedure due to the correlation between induced neuroplasticity and the provocation of cravings prior to rTMS treatment (Tendler et al., 2019). It would be unreasonable in a formal-medical setting for a patient receiving rTMS therapy to undergo a standardized provocation procedure before each rTMS session; therefore, it would have been best to exempt the usage of a provocation or motivation procedure in the study.
All factors considered, the study conducted by Zangen et al. has demonstrated the case for rTMS technology in the treatment of smoking cessation, producing results which—despite being recorded on a relatively small scale—have not gone unnoticed. As a result of the Zangen study, rTMS has received FDA approval for the treatment of smoking cessation. Their research serves as a critical milestone for the future of rTMS, not only as a treatment for smoking cessation, but as a possible prescription to psychiatric and neurological disorders for which treatments remain limited.
References
rTMS is a non-invasive procedure for the treatment of psychological, psychiatric, and neurological disorders, which has been in practice since 2008 (Mann and Malhi, 2021; Zangen et al., 2021). rTMS therapy constitutes a large electrically charged coil to be placed around the scalp of a patient. Once activated, the coil produces rapid electrical pulses varying in amplitude, which perpetuate a stable electromagnetic field around a specified region of the brain (Roth et al., 2002). Electrical currents offset by the electromagnetic field penetrate cortical tissue, inducing neuronal depolarization (Zangen et al., 2021) and resulting in protensive neuroplastic transformations when administered consistently (Flint, 2021, p. 153). Previous studies exploring the efficacy of rTMS in treating clinical depression have indicated that rTMS treatment directed to the left dorsolateral prefrontal cortex—a part of the brain which experiences increased activity in patients who are clinically depressed—has been associated with remission of depressive symptoms (Baeken et al., 2019). As forms of TMS therapy have been approved by the U.S. Food and Drug Administration to treat obsessive-compulsive disorder and major depressive disorder, a study conducted by Zangen and colleagues aimed to demonstrate the use of TMS therapy as a possible treatment for smoking cessation.
Zangen and his team employed the use of a double-blind procedural study comprising adults, aged 22 to 70, who suffer from tobacco use disorder and stated intentions to terminate their addiction (Zangen et al., 2021). Participants were randomly assigned into an active group that received rTMS treatment and a sham group that received a placebo treatment. rTMS treatment for the active group was directed to the lateral and insular cortices of the subjects’ brains. During an initial three-week period, both groups were administered rTMS treatment (active or sham) five days a week; groups were also given treatment once a week during an additional three-week follow-up period. Before the administration of each treatment, participants in both groups experienced a five-minute provocation session in which participants were treated with visual and audiovisual stimuli, which were designed to provoke cigarette cravings. After each rTMS session, a motivational speech supporting smoking cessation was read to each participant. The use of a provocation and motivation procedure before and after rTMS treatment by Zangen and his team was influenced by research suggesting that mild provocation before TMS treatment may condition brain areas to be more acquiescent to plastic change (Tendler et al., 2019). Zangen et al., however, did not measure the influence of a provocation procedure on the effectiveness of rTMS therapy, or on the behavior demonstrated by the sham group, potentially confounding results. During the treatment period for the study, the number of cigarettes smoked by each participant was self-reported through a daily diary, and nicotine levels were confirmed by a urine sample which was tested weekly for cotinine levels. The choice to test for cotinine levels reflects an improvement to previous clinical trials in smoking cessation medication which utilized carbon monoxide breath testing, which would only confirm cessation for hours surrounding treatment in contrast to cotinine testing which would be able to confirm abstinence for days. Levels of craving were recorded by Zangen and associates once before and once after each provocation procedure, as well as once after each rTMS administration. After the three-week treatment period and consecutive follow-up, Zangen et al. (2021) discovered that the active group, which received daily rTMS therapy directed at the lateral prefrontal and insular cortices, had been two times more likely to abstain from smoking tobacco products than the sham (placebo) group. Zangen and colleagues also found that the active group who received rTMS treatment was less affected by the pre-treatment provocation procedure in relation to the sham group following the first day of treatment.
Despite the promising results Zangen and his team recorded during the experiment, the study did have its shortcomings. When compared to trials of medicines such as varenicline and bupropion, which are Food and Drug Administration (FDA) approved for smoking cessation, the rTMS study had a relatively small sample size and short follow-up period (Zangen et al., 2021). A larger sample size would allow for the study conducted by Zangen and his team to serve as a more efficacious comparison to other studies of treatment for smoking cessation and would permit participants examined during the follow-up period to best represent the behavior of a population of patients diagnosed with TBD. Zangen and team also do not factor in the degree the provocation and motivation procedure influences cessation and craving in both the active and sham groups. The results collected in the study are confounded by the presence of a provocation and motivation procedure due to the correlation between induced neuroplasticity and the provocation of cravings prior to rTMS treatment (Tendler et al., 2019). It would be unreasonable in a formal-medical setting for a patient receiving rTMS therapy to undergo a standardized provocation procedure before each rTMS session; therefore, it would have been best to exempt the usage of a provocation or motivation procedure in the study.
All factors considered, the study conducted by Zangen et al. has demonstrated the case for rTMS technology in the treatment of smoking cessation, producing results which—despite being recorded on a relatively small scale—have not gone unnoticed. As a result of the Zangen study, rTMS has received FDA approval for the treatment of smoking cessation. Their research serves as a critical milestone for the future of rTMS, not only as a treatment for smoking cessation, but as a possible prescription to psychiatric and neurological disorders for which treatments remain limited.
References
- American Psychiatric Association. (2022). Substance-Related and Addictive Disorders. In Diagnostic and statistical manual of mental disorders (5th ed., text rev.). https://doi.org/10.1176/appi.books.9780890425787.x16_Substance_Related_Disorders
- Baeken, C., Brem, A. K., Arns, M., Brunoni, A. R., Filipčić, I., Ganho-Ávila, A., ... & Bennabi, D. (2019). Repetitive transcranial magnetic stimulation treatment for depressive disorders: current knowledge and future directions. Current opinion in psychiatry, 32(5), 409.
- Flint, P. W. (2021). Tinnitus and Hyperacusis. In Cummings otolaryngology: Head and Neck Surgery (Seven, pp. 153–153). essay, Elsevier.
- Mann, S. K., & Malhi, N. K. (2021). Repetitive transcranial magnetic stimulation.
- Roth, Y., Zangen, A., & Hallett, M. (2002). A coil design for transcranial magnetic stimulation of deep brain regions. Journal of clinical neurophysiology: official publication of the American Electroencephalographic Society, 19(4), 361–370. https://doi.org/10.1097/00004691-200208000-00008.
- Tendler, A., Sisko, E., Barnea-Ygael, N., Zangen, A., & Storch, E. A. (2019). A Method to Provoke Obsessive Compulsive Symptoms for Basic Research and Clinical Interventions. Frontiers in psychiatry, 10, 814. https://doi.org/10.3389/fpsyt.2019.00814
- 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.