Accelerated Intermittent Theta Burst Stimulation in Smoking Cessation: Placebo Effects Equal to Active Stimulation When Using Advanced Placebo Coil Technology

Abstract

Smoking is currently one of the main public health problems. Smoking cessation is known to be difficult for most smokers because of nicotine dependence. Repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) has been shown to be effective in the reduction of nicotine craving and cigarette consumption. Here, we evaluated the efficacy of accelerated intermittent theta burst stimulation (aiTBS; four sessions per day for 5 consecutive days) over the left DLPFC in smoking cessation, and we investigated whether the exposure to smoking-related cues compared to neutral cues during transcranial magnetic stimulation (TMS) impacts treatment outcome. A double-blind, randomized, controlled study was conducted in which 89 participants (60 males and 29 females; age 45.62 ± 13.42 years) were randomly divided into three 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. Our results suggest that aiTBS is a tolerable treatment. All treatment groups equally reduced cigarette consumption, nicotine dependence, craving and perceived stress. The effect on nicotine dependence, general craving and perceived stress lasted for at least 1 week after the end of treatment. Active aiTBS over the left DLPFC, combined with smoking related cues, is as effective as active aiTBS combined with neutral cues as well as placebo aiTBS in smoking cessation. These findings extend the results of previous studies indicating that TMS therapy is associated with considerably large placebo effects and that these placebo effects may be further increased when using advanced placebo coil technology.Clinical Trial Registrationwww.clinicaltrials.gov, identifier NCT05271175.

Accelerated intermittent theta burst stimulation in smoking cessation: No differences between active and placebo stimulation when using advanced placebo coil technology. A double-blind follow-up study

“…The use of electrical stimulation in combination with a placebo TMS coil has been reported as an effective TMS approach to achieve placebo condition ( Duecker & Sack, 2015 ). In Mikellides and colleagues study (2022) , both, active and placebo, stimulation were performed using an advanced double blind placebo stimulation technology, the figure-of-eight coil (Coil Cool-B65 A/P), which is capable to mimic both, the visual and auditory experience of active TMS as well as similar somatosensory skin sensation. Using a low intensity current stimulator built into the coil and a pair of surface electrodes placed just below the hairline on the scalp of each participant, this coil is designed to support true “double blinded” clinical trials as it can produce active and placebo stimulation by flipping it.…”

“…Using a low intensity current stimulator built into the coil and a pair of surface electrodes placed just below the hairline on the scalp of each participant, this coil is designed to support true “double blinded” clinical trials as it can produce active and placebo stimulation by flipping it. The use of a novel and advanced placebo coil technology in Mikellides et al (2022) study may contribute to the fact both active and placebo stimulation were highly effective in reducing cigarette consumption and craving.…”

“…Detailed methods of our randomized controlled trial (RCT) have been reported previously ( Mikellides et al, 2022 ). We performed a multi-arm parallel group, double-blinded, randomized, controlled study, where eighty-nine participants were randomly allocated into three groups: the first group received active aiTBS stimulation combined with neutral videos (TMS&N), the second group received active aiTBS stimulation combined with smoking-related videos (TMS&N) and the last group received placebo stimulation (Placebo) combined with smoking-related videos.…”

“…Nevertheless, the type of treatment group and/or the interaction effect between treatment time and treatment group were not statistically significant. Thus, the results showed that both, active as well as placebo stimulation, did not affect immediate treatment outcome ( Mikellides et al, 2022 ).…”

“…We recently conducted a double-blind randomized control trial to evaluate the effect of active and placebo accelerated intermittent theta burst stimulation (aiTBS) (4 sessions per day for 5 consecutive days) over the left DLPFC in smoking cessation and the impact of smoking-related or neutral cues, during the stimulation, in treatment outcome ( Mikellides et al, 2022 ). The study participants were divided into three groups (TMS&N group: active aiTBS stimulation combined with neutral videos; TMS&S group: active aiTBS stimulation combined with smoking-related videos; Placebo group: placebo stimulation combined with smoking-related videos).…”