Accelerated iTBS in Smoking Cessation

Cigarette smoking is one of the foremost causes of preventable disease and premature death. In 2014, 68% of adult smokers wanted to quit smoking and in 2017, 55.1% of adult smokers had made a quit attempt. However, only a small percentage of adult smokers (7,4%) achieved to quit smoking. Transcranial magnetic stimulation (TMS) is a novel, powerful, non-invasive brain stimulation therapy. This study used Theta Burst Stimulation (TBS), a newer form of rTMS protocol that can be delivered in a shorter duration compared to the standard rTMS protocol, while delivering a comparable number of pulses. It is a tolerable, powerful, and useful tool in non-invasive brain stimulation therapies. This double-blind randomized control trial evaluated the efficacy of 4 iTBS sessions per day during 5 consecutive days over the left DLPFC in smoking cessation. Moreover, it investigated whether the exposure to smoking-related cues during the rTMS treatment, compared to neutral cues impact cigarette craving.

Cigarette smoking is one of the foremost causes of preventable disease and premature death. In 2014, 68% of adult smokers wanted to quit smoking and in 2017, 55.1% of adult smokers had made a quit attempt. However, only a small percentage of adult smokers (7,4%) achieved to quit smoking. Behavioral and psychological interventions, pharmacological interventions as well as nicotine replacement therapy are some of the most used interventions for smoking cessation with medium to low success rates. Nonetheless, in recent years there has been growing interest in new, alternative, and effective treatments for smoking cessation. Transcranial magnetic stimulation (TMS) is a novel, powerful, non-invasive brain stimulation therapy. TMS non-invasively (transcranially) delivers magnetic pulses to a brain region, inducing electric a current that can depolarize neurons and induce action potentials. This study used Theta Burst Stimulation (TBS), a newer form of rTMS protocol that can be delivered in a shorter duration compared to the standard rTMS protocol, while delivering a comparable number of pulses. It is a tolerable, powerful, and useful tool in non-invasive brain stimulation therapies. This double-blind randomized control trial evaluated the efficacy of 4 iTBS sessions per day during 5 consecutive days over the left DLPFC in smoking cessation. Moreover, it investigated whether the exposure to smoking-related cues during the rTMS treatment, compared to neutral cues impact cigarette craving. The investigators hypothesized that twenty sessions of accelerated theta burst simulation over the left DLPFC while exposed to smoking-related cues, would reduce cigarette consumption and cigarette cravings, accompanied by reduced stress and motivation to quit smoking, compared to both active and sham stimulation with neutral-cues. A total of 104 cigarettes smokers, who wanted to quit smoking, were enrolled and were randomly divided into the three experimental groups: the first group received active aiTBS stimulation while watching neutral videos, the second group received active aiTBS stimulation while watching smoking-related videos and the last group received sham stimulation while watching smoking-related videos. Primary and secondary measurements were performed at the baseline, during the treatment period, at one week, one month and six months post rTMS treatment.

An accelerated iTBS (aiTBS) treatment (4 sessions with 30 minutes break between them) was administered daily for a 5-day period over the left DLPFC using the MagVenture Cool-B65 Active/Placebo (A/P) coil.

An accelerated iTBS (aiTBS) treatment (4 sessions with 30 minutes break between them) was administered daily for a 5-day period over the left DLPFC using the MagVenture Cool-B65 Active/Placebo (A/P) coil. The MagVenture Cool-B65 Active/Placebo (A/P) coil is designed to support true "double blinded" clinical trials as it can produce active and placebo stimulation by flipping the coil and can mimic tapping sensation during placebo condition During the sham condition, the coil produced the same sound as the real active condition but did not deliver any stimulation on the side of the participant's skull.

Participants were required to record the number of cigarettes smoked after the completion of the 1st day of treatment until before the first session on the second day of treatment. Participants were asked not to smoke during the breaks of the 4 daily rTMS sessions

Participants were required to record the number of cigarettes smoked after the completion of the 2nd day of treatment until before the first session on the 3rd day of treatment. Participants were asked not to smoke during the breaks of the 4 daily rTMS sessions

Participants were required to record the number of cigarettes smoked after the completion of the 3rd day of treatment until before the first session on the 4th day of treatment. Participants were asked not to smoke during the breaks of the 4 daily rTMS sessions

Participants were required to record the number of cigarettes smoked after the completion of the 4th day of treatment until before the first session on the 5th day of treatment . Participants were asked not to smoke during the breaks of the 4 daily rTMS sessions

CO level was measured using the piCO Smokerlyzer breath carbon monoxide meter device prior to the first rTMS session.

Fagerström test for Nicotine Dependence (FTND) is a short, self-report measure that assesses nicotine dependence. It contains six questions, and the total score is calculated as a sum of these six questions. The scores vary from 0 to 10, with lower scores indicating lower dependence on nicotine.

Fagerström test for Nicotine Dependence (FTND) is a short, self-report measure that assesses nicotine dependence. It contains six questions, and the total score is calculated as a sum of these six questions. The scores vary from 0 to 10, with lower scores indicating lower dependence on nicotine.

Fagerström test for Nicotine Dependence (FTND) is a short, self-report measure that assesses nicotine dependence. It contains six questions, and the total score is calculated as a sum of these six questions. The scores vary from 0 to 10, with lower scores indicating lower dependence on nicotine.

Fagerström test for Nicotine Dependence (FTND) is a short, self-report measure that assesses nicotine dependence. It contains six questions, and the total score is calculated as a sum of these six questions. The scores vary from 0 to 10, with lower scores indicating lower dependence on nicotine.

Fagerström test for Nicotine Dependence (FTND) is a short, self-report measure that assesses nicotine dependence. It contains six questions, and the total score is calculated as a sum of these six questions. The scores vary from 0 to 10, with lower scores indicating lower dependence on nicotine.

The Visual Analogue Scale (VAS) is a psychometric measurement instrument that measures symptom severity on a continuous scale. The VAS can be quickly and repeatedly administered between tasks and it has been used extensively in smoking research with TMS. We used the VAS to assess smoking craving by asking participants to respond to the question "How much do you want to smoke right now?", on a scale from 0 "no craving" to 100 "most craving ever experienced" by choosing a response on a visual scale given in front of them on a tablet.

The Visual Analogue Scale (VAS) is a psychometric measurement instrument that measures symptom severity on a continuous scale. The VAS can be quickly and repeatedly administered between tasks and it has been used extensively in smoking research with TMS. We used the VAS to assess smoking craving by asking participants to respond to the question "How much do you want to smoke right now?", on a scale from 0 "no craving" to 100 "most craving ever experienced" by choosing a response on a visual scale given in front of them on a tablet. The average of the eight VAS scores, measured prior and post each of the four sessions on Day 1.

The Visual Analogue Scale (VAS) is a psychometric measurement instrument that measures symptom severity on a continuous scale. The VAS can be quickly and repeatedly administered between tasks and it has been used extensively in smoking research with TMS. We used the VAS to assess smoking craving by asking participants to respond to the question "How much do you want to smoke right now?", on a scale from 0 "no craving" to 100 "most craving ever experienced" by choosing a response on a visual scale given in front of them on a tablet. The average of the eight VAS scores, measured prior and post each of the four sessions on Day 2.

The Visual Analogue Scale (VAS) is a psychometric measurement instrument that measures symptom severity on a continuous scale. The VAS can be quickly and repeatedly administered between tasks and it has been used extensively in smoking research with TMS. We used the VAS to assess smoking craving by asking participants to respond to the question "How much do you want to smoke right now?", on a scale from 0 "no craving" to 100 "most craving ever experienced" by choosing a response on a visual scale given in front of them on a tablet. The average of the eight VAS scores, measured prior and post each of the four sessions on Day 3.

The Visual Analogue Scale (VAS) is a psychometric measurement instrument that measures symptom severity on a continuous scale. The VAS can be quickly and repeatedly administered between tasks and it has been used extensively in smoking research with TMS. We used the VAS to assess smoking craving by asking participants to respond to the question "How much do you want to smoke right now?", on a scale from 0 "no craving" to 100 "most craving ever experienced" by choosing a response on a visual scale given in front of them on a tablet. The average of the eight VAS scores, measured prior and post each of the four sessions on Day 4.

The Visual Analogue Scale (VAS) is a psychometric measurement instrument that measures symptom severity on a continuous scale. The VAS can be quickly and repeatedly administered between tasks and it has been used extensively in smoking research with TMS. We used the VAS to assess smoking craving by asking participants to respond to the question "How much do you want to smoke right now?", on a scale from 0 "no craving" to 100 "most craving ever experienced" by choosing a response on a visual scale given in front of them on a tablet. The average of the eight VAS scores, measured prior and post each of the four sessions on Day 5.

Tobacco Craving Questionnaire-Short Form (TCQ-SF) is a self-report measure that assesses tobacco craving in four dimensions. Each factor scale contains three items. TCQ-SF items were rated on a Likert scale of 1 (strongly disagree) to 7 (strongly agree). Total scores vary from 12 to 84, by summing the 12 items and the scores for each factor scale vary from 3 to 21 by summing the three items in each factor scale. A high score indicates high tobacco craving.

Tobacco Craving Questionnaire-Short Form (TCQ-SF) is a self-report measure that assesses tobacco craving in four dimensions. Each factor scale contains three items. TCQ-SF items were rated on a Likert scale of 1 (strongly disagree) to 7 (strongly agree). Total scores vary from 12 to 84, by summing the 12 items and the scores for each factor scale vary from 3 to 21 by summing the three items in each factor scale. A high score indicates high tobacco craving.

Tobacco Craving Questionnaire-Short Form (TCQ-SF) is a self-report measure that assesses tobacco craving in four dimensions. Each factor scale contains three items. TCQ-SF items were rated on a Likert scale of 1 (strongly disagree) to 7 (strongly agree). Total scores vary from 12 to 84, by summing the 12 items and the scores for each factor scale vary from 3 to 21 by summing the three items in each factor scale. A high score indicates high tobacco craving.

Tobacco Craving Questionnaire-Short Form (TCQ-SF) is a self-report measure that assesses tobacco craving in four dimensions. Each factor scale contains three items. TCQ-SF items were rated on a Likert scale of 1 (strongly disagree) to 7 (strongly agree). Total scores vary from 12 to 84, by summing the 12 items and the scores for each factor scale vary from 3 to 21 by summing the three items in each factor scale. A high score indicates high tobacco craving.

Tobacco Craving Questionnaire-Short Form (TCQ-SF) is a self-report measure that assesses tobacco craving in four dimensions. Each factor scale contains three items. TCQ-SF items were rated on a Likert scale of 1 (strongly disagree) to 7 (strongly agree). Total scores vary from 12 to 84, by summing the 12 items and the scores for each factor scale vary from 3 to 21 by summing the three items in each factor scale. A high score indicates high tobacco craving.

Perceived Stress Scale-4 (PSS-4) is a self-report measure that is used to assess psychological stress. PSS-4 items were rated on a Likert scale, ranging from 0 to 4, with those on the positive subscale scored in reverse and the total score was calculated as a sum of these items. The scores vary from 0-16, with a higher score indicating higher perceived stress.

Perceived Stress Scale-4 (PSS-4) is a self-report measure that is used to assess psychological stress. PSS-4 items were rated on a Likert scale, ranging from 0 to 4, with those on the positive subscale scored in reverse and the total score was calculated as a sum of these items. The scores vary from 0-16, with a higher score indicating higher perceived stress.

Perceived Stress Scale-4 (PSS-4) is a self-report measure that is used to assess psychological stress. PSS-4 items were rated on a Likert scale, ranging from 0 to 4, with those on the positive subscale scored in reverse and the total score was calculated as a sum of these items. The scores vary from 0-16, with a higher score indicating higher perceived stress.

Perceived Stress Scale-4 (PSS-4) is a self-report measure that is used to assess psychological stress. PSS-4 items were rated on a Likert scale, ranging from 0 to 4, with those on the positive subscale scored in reverse and the total score was calculated as a sum of these items. The scores vary from 0-16, with a higher score indicating higher perceived stress.

Perceived Stress Scale-4 (PSS-4) is a self-report measure that is used to assess psychological stress. PSS-4 items were rated on a Likert scale, ranging from 0 to 4, with those on the positive subscale scored in reverse and the total score was calculated as a sum of these items. The scores vary from 0-16, with a higher score indicating higher perceived stress.

Participants were asked to estimate how motivated they were to quit smoking from 0% to 100%. Τhe possible answers were: 0%, 25%, 50%, 75% and 100%. Higher values reflect greater motivation to quit smoking.

Participants were asked to estimate how motivated they were to quit smoking from 0% to 100%. Τhe possible answers were: 0%, 25%, 50%, 75% and 100%. Higher values reflect greater motivation to quit smoking.

Participants were asked to estimate how motivated they were to quit smoking from 0% to 100%. Τhe possible answers were: 0%, 25%, 50%, 75% and 100%. Higher values reflect greater motivation to quit smoking.

Participants were asked to estimate how motivated they were to quit smoking from 0% to 100%. Τhe possible answers were: 0%, 25%, 50%, 75% and 100%. Higher values reflect greater motivation to quit smoking.

Participants were asked to estimate how motivated they were to quit smoking from 0% to 100%. Τhe possible answers were: 0%, 25%, 50%, 75% and 100%. Higher values reflect greater motivation to quit smoking.

Inclusion Criteria: aged 18-70 native or fluent Greek speaker. Exclusion Criteria: mental objects or implants in the brain, skull or near head (e.g., pacemakers, metal plates) past or current of diagnosis of neurological or psychiatric disorder use of psychiatric medication past or current drug or alcohol abuse, other than nicotine use of IQOS ("I Quit Original Smoking") or electronic cigarettes (e-cigarettes).

Mikellides G, Michael P, Psalta L, Stefani A, Schuhmann T, Sack AT. Accelerated Intermittent Theta Burst Stimulation in Smoking Cessation: Placebo Effects Equal to Active Stimulation When Using Advanced Placebo Coil Technology. Front Psychiatry. 2022 May 24;13:892075. doi: 10.3389/fpsyt.2022.892075. eCollection 2022.