European Journal of Cardiovascular Medicine

Tobacco smoking remains one of the leading preventable causes of morbidity and mortality worldwide, contributing substantially to cardiovascular disease, chronic respiratory disease, cancer, and premature death. According to the World Health Organization, more than eight million deaths annually are attributable to tobacco use, making smoking cessation a major public health priority worldwide [1].

Nicotine dependence is a chronic relapsing disorder characterized by compulsive tobacco use despite harmful consequences. The neurobiology of nicotine addiction involves dysregulation of multiple interconnected brain regions including the prefrontal cortex, insular cortex, anterior cingulate cortex, ventral tegmental area, and nucleus accumbens. These neural circuits regulate reward processing, craving, executive control, and reinforcement learning mechanisms that sustain addictive behaviour [2,3].

Although pharmacological interventions such as nicotine replacement therapy, bupropion, and varenicline have demonstrated efficacy in smoking cessation, long-term abstinence rates remain suboptimal, with relapse occurring in a substantial proportion of patients within the first year of treatment [4,5]. Consequently, there has been growing interest in neuromodulation techniques that directly target addiction-related neural circuitry.

Transcranial Magnetic Stimulation (TMS) is a non-invasive neuromodulation technique capable of altering cortical excitability through electromagnetic induction. Deep Transcranial Magnetic Stimulation (Deep TMS) represents an advancement over conventional repetitive TMS, allowing stimulation of broader and deeper cortical structures through specialized coil designs [6]. The United States Food and Drug Administration (US-FDA) cleared usage of H4 coil in smoking cessation in the year 2020. This is the only TMS intervention that has been approved in the addiction disorders. The H4 coil was specifically developed to target the bilateral insula and prefrontal cortex, regions strongly implicated in nicotine craving and addictive behaviours [7].

The insular cortex has emerged as a critical component in tobacco addiction. Neuroimaging and lesion studies have demonstrated that disruption of insular function can significantly reduce cigarette craving and facilitate smoking cessation, highlighting its importance as a therapeutic target [8,9]. By modulating both prefrontal executive control networks and insular craving circuits, Deep TMS may reduce cue-induced craving and improve abstinence outcomes.

The pivotal Multicenter randomized controlled trial conducted by Dinur-Klein et al. demonstrated significantly higher quit rates among smokers receiving active H4 coil Deep TMS compared with sham stimulation, leading to subsequent FDA clearance of Deep TMS as an aid for smoking cessation [10]. Subsequent studies have further supported the role of Deep TMS in reducing cigarette consumption, nicotine craving, and dependence severity [11,12].

Psychiatric comorbidities such as depression, psychotic disorders, obsessive-compulsive disorder, and alcohol use disorder are highly prevalent among smokers and are often associated with greater nicotine dependence and poorer cessation outcomes [13,14].

Therefore, the present observational study aimed to evaluate the clinical utility of H4 coil Deep TMS in reducing nicotine dependence among smokers in a real-world neuromodulation setting.

This was a retrospective observational study conducted at Asha Neuromodulation Clinics, and Asha Hospital, Hyderabad, Telangana, India. Study Population Patients presenting with nicotine dependence who underwent Deep TMS treatment using the BrainsWay H4 coil were included in the study. Both individuals with isolated nicotine dependence and those with coexisting psychiatric illnesses were eligible. Treatment Protocol Deep TMS was administered using the BrainsWay H4 coil targeting the bilateral insular and prefrontal cortices. Treatment parameters included: • Frequency: 10 Hz • Intensity: 120% resting motor threshold • Pulses per session: 1800 • Session duration: 18 minutes • Sessions per day: Two • Total treatment duration: Five consecutive days Resting motor threshold was determined from the right hand. Provocation procedures were introduced before treatment sessions beginning from the third or fourth session as per clinic protocol. Each Deep TMS session is preceded by a 2-minute provocation period during which the person is asked to handle a cigarette (preferably of his/her choice) and/or a lighter and develop a craving or a feeling to smoke. Provocation may produce anxiety in some patients. Hence, care was taken to ensure that provocation should not induce severe anxiety as rated above 7 on a Visual Analog Scale. Also, we recommended that one hour prior to the current H4 TMS session, the person should not have had a smoke, which could possibly reduce the craving during the current session. Adjunctive Treatment All patients received: • Motivational Enhancement Therapy (30 minutes per session; five sessions) that included personalized counselling, tobacco self-help guides, maintenance of craving diary, and education sessions on ill effects of tobacco consumption. • Standard dose Varenicline therapy that included Varenicline Therapy for 12 weeks treatment. 0.5 mg once daily dosage was given for 1-3 days, increased to 1 mg daily dose for next 4 days. Patients were advised to take 2 mg daily doses for the next 12 weeks. Outcome Measure Nicotine dependence severity was assessed using the Fagerström Test for Nicotine Dependence (FTND) at baseline and after completion of treatment. Primary outcome: • Change in FTND score from baseline to post-treatment. Statistical Analysis Data were entered into Microsoft Excel and analyzed descriptively. Continuous variables were expressed as mean ± standard deviation, while categorical variables were presented as frequencies and percentages. Percentage improvement was calculated from baseline FTND scores.

A total of 49 patients who underwent H4 coil Deep TMS for nicotine dependence were included in the analysis. The mean age of participants was 31.82 ± 9.80 years (range: 18–56 years). Most patients were male, reflecting the typical demographic profile of individuals seeking treatment for tobacco dependence in clinical settings.

The study population included patients with isolated nicotine dependence as well as individuals with psychiatric comorbidities such as depression, obsessive-compulsive disorder (OCD), psychotic disorders, and alcohol use disorder. Psychiatric comorbidities were not specifically targeted during Deep TMS treatment, and the intervention was focused solely on smoking cessation.

Table 1. Baseline Characteristics of Study Participants (N = 49)

Narrative

The study population predominantly consisted of young and middle-aged adults with moderate-to-severe nicotine dependence. All patients received a standardized Deep TMS protocol consisting of ten sessions administered over five consecutive days. Treatment delivery was uniform across participants, ensuring consistency in stimulation parameters and exposure.

Table 2. Fagerström Test for Nicotine Dependence Scores Before and After Treatment

Narrative

A substantial reduction in nicotine dependence severity was observed following Deep TMS treatment. The mean FTND score decreased from 7.02 at baseline to 2.89 after treatment, representing an average reduction of more than four points. This reduction indicates clinically meaningful improvement in nicotine dependence severity among the treated participants.

Table 3. Percentage Improvement Following Deep TMS Treatment

Narrative

The average percentage improvement in nicotine dependence was approximately 59%, demonstrating a robust treatment response across the study cohort. Some participants achieved complete resolution of measurable nicotine dependence scores, while even the least responsive individuals demonstrated clinically relevant reductions.

The present observational study evaluated the effectiveness of H4 coil Deep TMS in reducing nicotine dependence among smokers treated in routine clinical practice. Following treatment, a substantial reduction in nicotine dependence severity was observed, with mean FTND scores decreasing from 7.02 ± 1.30 at baseline to 2.89 ± 1.30 after treatment. The average reduction of more than four points corresponded to an improvement of approximately 59%, indicating a clinically meaningful treatment response. The findings are consistent with the growing body of evidence supporting Deep TMS as a promising intervention for nicotine addiction. The neurobiological rationale for Deep TMS is based on modulation of the insular and prefrontal cortical regions that regulate craving, reward processing, decision-making, and inhibitory control [2,3]. Functional neuroimaging studies have demonstrated increased activation of these regions during nicotine craving states, suggesting that targeted neuromodulation may attenuate addictive behaviours [15]. One of the most influential studies evaluating Deep TMS for smoking cessation was the Multicenter randomized controlled trial by Dinur-Klein et al. [10]. The authors reported significantly greater smoking abstinence rates and reduced cigarette consumption in participants receiving active H4 coil stimulation compared with sham treatment. The present study corroborates these findings in a real-world clinical population and demonstrates meaningful reductions in nicotine dependence scores following treatment. The effectiveness of the H4 coil may be attributed to its ability to stimulate deeper cortical structures compared with conventional figure-of-eight coils. Deep TMS can modulate extensive cortical-subcortical networks implicated in addiction, thereby influencing both craving-related and executive-control mechanisms [6,7]. This broader stimulation profile may contribute to the favourable outcomes observed in smoking cessation studies. Tobacco dependence is disproportionately prevalent among individuals with mental illness, who account for a substantial proportion of total cigarette consumption worldwide [13]. Smokers with depression, schizophrenia spectrum disorders, obsessive-compulsive disorder, and alcohol use disorder often exhibit greater nicotine dependence severity and lower cessation success rates compared with the general population [14,16]. The present results also support previous evidence indicating that neuromodulation may serve as a valuable adjunct to conventional smoking cessation strategies. All participants received Motivation Enhancement Therapy and Varenicline in addition to Deep TMS. Combination approaches are increasingly recognized as important because tobacco addiction involves biological, psychological, and behavioural determinants [5,17]. Integrating pharmacotherapy, behavioural interventions, and neuromodulation may therefore maximize treatment outcomes. Another noteworthy aspect of the current study was the abbreviated treatment schedule. Participants received ten Deep TMS sessions over five days, whereas the FDA-cleared protocol generally involves eighteen treatment sessions [10]. Despite this shorter treatment duration, substantial reductions in nicotine dependence were achieved. These findings suggest that condensed treatment schedules may retain clinical effectiveness while improving patient convenience and treatment adherence. However, direct comparisons between abbreviated and standard protocols require further investigation. The mean percentage improvement of approximately 59% observed in this cohort is clinically encouraging and compares favourably with previously reported reductions in craving and smoking behaviour following Deep TMS interventions [11,12,18]. Such improvements may reflect successful modulation of neural circuits involved in cue reactivity and compulsive tobacco use. The study possesses several strengths. It reflects routine clinical practice, includes patients with complex psychiatric profiles frequently excluded from randomized trials, and evaluates outcomes using a widely accepted measure of nicotine dependence. Consequently, the findings provide valuable information regarding the practical applicability of Deep TMS in real-world smoking cessation programs. Nevertheless, several limitations should be considered. The observational design precludes causal inference and lacks a sham-control group. The sample size was relatively modest and derived from a single center. Follow-up data were unavailable, preventing evaluation of long-term abstinence and relapse rates. Furthermore, biochemical verification of smoking cessation was not performed. The concurrent administration of varenicline and motivational therapy may also have influenced treatment outcomes. Future randomized controlled trials involving larger samples, longer follow-up periods, and biochemical confirmation of abstinence are warranted. Additional research should also explore the effectiveness of Deep TMS in specific psychiatric populations and determine whether extending treatment to the standard eighteen-session protocol yields superior long-term outcomes [19-23]. Overall, the findings of the present study add to the growing evidence supporting H4 coil Deep TMS as an effective adjunctive intervention for smoking cessation.

H4 coil Deep Transcranial Magnetic Stimulation (Deep TMS) demonstrated promising clinical utility as an adjunctive treatment for nicotine dependence in this real-world observational cohort. Treatment was associated with a substantial reduction in Fagerström Test for Nicotine Dependence scores, with an average improvement of approximately 59% following a condensed five-day treatment protocol. Meaningful clinical benefits were observed not only in individuals with isolated nicotine dependence but also among patients with coexisting psychiatric disorders, including depression, obsessive-compulsive disorder, psychotic disorders, and alcohol use disorder.

The findings support the role of Deep TMS as a non-invasive neuromodulation approach targeting addiction-related neural circuits involving the bilateral insula and prefrontal cortex. Importantly, favourable outcomes were achieved despite the use of a shortened treatment schedule compared with the standard FDA-approved protocol, suggesting potential feasibility in routine clinical practice.

Although the observational design, absence of long-term follow-up, and concurrent use of varenicline and motivational therapy limit definitive conclusions regarding efficacy, the results indicate that H4 coil Deep TMS may represent a valuable addition to comprehensive smoking cessation programs. Larger controlled studies with extended follow-up are warranted to establish long-term abstinence rates, determine optimal treatment parameters, and further evaluate outcomes in patients with psychiatric comorbidities.

1.      WHO Report on the Global Tobacco Epidemic. Geneva: WHO; 2023.

2.      Benowitz NL. Nicotine addiction. N Engl J Med. 2010;362:2295-303.

3.      Koob GF, Volkow ND. Neurobiology of addiction. Lancet Psychiatry. 2016;3:760-73.

4.      Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation. Cochrane Database Syst Rev. 2013;5:CD009329.

5.      Fiore MC, Jaén CR, Baker TB, et al. Treating Tobacco Use and Dependence: 2008 Update.

6.      Levkovitz Y, Roth Y, Harel EV, et al. Deep TMS over the prefrontal cortex. Clin Neurophysiol. 2007;118:2730-44.

7.      Roth Y, Amir A, Levkovitz Y, Zangen A. Three-dimensional distribution of magnetic fields induced by H-coils. J Clin Neurophysiol. 2007;24:31-38.

8.      Naqvi NH, Rudrauf D, Damasio H, Bechara A. Damage to the insula disrupts addiction to cigarette smoking. Science. 2007;315:531-34.

9.      Naqvi NH, Bechara A. The insula and drug addiction. Neuropharmacology. 2010;59:435-41.

10.   Dinur-Klein N, Dannon P, Hadar A, et al. Smoking cessation induced by Deep TMS. World Psychiatry. 2014;13:87-92.

11.   Zangen A, Moshe H, Martinez D, et al. Repetitive transcranial magnetic stimulation for smoking cessation. Addiction. 2021;116:1908-19.

12.   Tendler A, Barnea-Ygael N, Roth Y, et al. Deep TMS for smoking cessation. Brain Stimul. 2016;9:644-45.

13.   Prochaska JJ. Smoking and mental illness. N Engl J Med. 2011;365:196-98.

14.   Lasser K, Boyd JW, Woolhandler S, et al. Smoking and mental illness. JAMA. 2000;284:2606-10.

15.   Brody AL, Mandelkern MA, London ED, et al. Neural substrates of resisting craving. Biol Psychiatry. 2007;62:642-49.

16.   Cook BL, Wayne GF, Kafali EN, et al. Trends in smoking among adults with mental illness. Am J Public Health. 2014;104:e17-e25.

17.   Rigotti NA. Strategies to help smokers quit. N Engl J Med. 2012;366:2575-84.

18.   Li X, Hartwell KJ, Owens M, et al. Repetitive TMS and smoking cessation. Drug Alcohol Depend. 2013;133:740-46.

19.   Kohli AS, Goyal JD, Jamatia K, Kaur GP, Syed Afroz K, Anoosha M, Tiwari R. Clinical and radiographic evaluation of different techniques for impacted canine exposure. Journal of Pharmacy and Bioallied Sciences. 2025. doi:10.4103/jpbs.jpbs_1462_24.

20.   Reddy KH, Syed AK, Alivelu D, Danda H, Alla R. A randomized split mouth clinical trial of the application of the desensitizer agents for tooth sensitivity. International Journal of Research in Medical Sciences. 2021;9:2430-4.

21.   Dixit H, Agrawal D, Gill SK, Tiwari R, Syed AK, Patri KC. Nutritional Status and Quality of Life in Post-Chemoradiotherapy Oral Cancer Patients: A Clinical Study. J AdvMed Dent Scie Res 2025; 13(10):14-19.

22.   Chinthapally V, Tiwari R, Tiwari HD, Syed AK. Assessment of Bone Healing Following Buccal Gutter vs. Lingual Split Technique in Impacted Mandibular Third Molar Removal: A Prospective Comparative Clinical and Radiographic Study. J Adv Med Dent Scie Res 2019;7(6): 253-258.

Tiwari R, Chinthapally V, Dixit H, Mahajan A, Syed AK. Correlation between sugar consumption and caries experience among high school students a cross-sectional study. J Adv Med Dent Scie Res 2023;11(7):108-113.