Smoking Cessation in Primary Care: A Narrative Review of Evidence-Based Treatment,Emerging Technology,and Harm Reduction Approaches

Evidence-Based Foundations of Smoking Cessation

US clinical practice guidance for tobacco smoking cessation in adults,^9,13,14 urges healthcare professionals to engage all adult patients about tobacco use and explore cessation. These guidelines support combined behavioral counseling and FDA-approved pharmacotherapy as the most effective approach for smoking cessation. Pharmacotherapy improves cessation outcomes compared with placebo or minimal support, and counseling plus medication increases quit rates more than either modality alone (see Tables 1 and 2).

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Table 2.

Pharmacotherapies for Smoking Cessation

Medication	FDA approved	Mechanism	Clinical role	Common adverse effects	Key considerations
Nicotine Replacement Therapy (patch, gum, lozenge, nasal spray)	Yes	Nicotine receptor agonist	First-line	Skin irritation, insomnia (patch); oral irritation (gum/lozenge)	Combination (patch + short-acting) improves efficacy
Bupropion SR	Yes	NE/DA reuptake inhibitor; nAChR antagonist	Alternative/adjunct	Insomnia, dry mouth	Contraindicated in seizure risk and eating disorders
Varenicline	Yes	Partial nAChR agonist	First-line (most effective single agent)	Nausea, vivid dreams	Monitor neuropsychiatric symptoms
Cytisine	No (US)	Partial nAChR agonist	Second-line (outside US)	Nausea, sleep disturbance	Increasing global use; emerging evidence
Nortriptyline	No	Tricyclic antidepressant	Second-line/off-label	Sedation, anticholinergic effects	Cardiac risk; overdose concern
Clonidine	No	α2-adrenergic agonist	Second-line/off-label	Hypotension, sedation	Taper to avoid rebound hypertension

The guidelines also inform us that when treating pregnant women who smoke, behavioral counseling is preferred as limited evidence and safety data constrain pharmacotherapy options.^9,13 In addition, the guidelines also remind us that although some randomized controlled trials (RCTs) suggest that nicotine e-cigarettes may support smoking cessation when paired with behavioral interventions,^9,13,16,17 they are not recommended as first-line therapy compared with FDA-approved pharmacotherapies.^16,17

Health-System Approaches in Primary Care

A key concept in tobacco dependence treatment is the “teachable moment,” defined as a life event or situation that increases receptivity to behavioral change. ³⁸ Teachable moments often occur, such as after an adverse health event attributable to smoking, but clinicians have opportunities for teachable moments to be created during every clinic visit. Effective counseling requires repeated education about both the short- and long-term effects of smoking, delivered in a safe and nonjudgmental manner. This process can also strengthen trust between patients and clinicians. These moments, in which health concerns become primary motivators for making a quit attempt, provide opportunities for HCPs to offer guidance and support for smoking cessation. Addressing motivation and barriers during these times with a personalized approach, indicating the benefits that exist from smoking cessation, and repeated advice to stop can significantly increase the likelihood of the patient quitting successfully. ^26,38-40

For primary care practices, ensuring tobacco treatment as a routine part of care delivery can take advantage of otherwise unrecognized potential ‘teachable moments’ to foster behavior change and cessation. Operationally, this can be facilitated by the use of automated tobacco-use documentation, prompts in the electronic health record, and opt-out referrals to treatment services. ⁴¹ A proactive and integrated system-based approach to follow-up can strengthen tobacco cessation efforts by ensuring more consistent patient engagement. Embedding screening and cessation support into routine care workflows lessens both clinician and patient burden, enabling sustained population -level impact without requiring intensive reassessment of tobacco use at every clinical encounter. Opt-out approaches facilitate greater enrollment for treatment as compared to opt-in approaches. ⁴² Programs that combine medication, counseling, and regular follow-up are more effective than single interventions.^38,43 A stepped-care model (see Figure 1) incorporates behavioral support, first-line pharmacotherapy, early and frequent follow-up, and adds additional treatments when needed. Within this model, patients achieving abstinence continue maintenance therapy and relapse prevention strategies, whereas patients who continue smoking despite initial treatment undergo reassessment, escalation of behavioral or pharmacologic support, and consideration of specialty referral or adjunctive therapies. These system-level approaches shift tobacco treatment from episodic intervention to routine care.^38,43OPEN IN VIEWER

Emerging and Innovative Treatment Approaches

Repetitive Transcranial Magnetic Stimulation (rTMS)

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that operationalizes this network-based approach by using magnetic fields to target cortical regions involved in craving, reward processing, and impulse control, particularly the dorsolateral prefrontal cortex. Both surface and deep TMS modalities have been studied, with deep TMS receiving FDA clearance for smoking cessation in 2020 (following prior approval for depression in 2008). In a pivotal multicenter randomized controlled trial, continuous quit rates were approximately 25% vs. 6% at 4 weeks and 28% vs. 12% at 18 weeks, while sustained abstinence approached one-third at 6 months.^48,49 Treatment is generally well tolerated, with the most common adverse effects including transient scalp discomfort, headache, lightheadedness, and facial muscle twitching. ⁴⁸ Given cost, access, and the need for specialized equipment, rTMS is best positioned as an adjunctive option for patients who have not achieved cessation with optimized pharmacotherapy and behavioral counseling.^{13,14,27,48,49}

In addition to TMS, which has been approved by the FDA, three additional investigational approaches are being explored for smoking cessation. These include Vagal Nerve Stimulation (VNS), EEG-based wearables and virtual reality, which are not currently recommended as routine primary care smoking cessation interventions and remain areas of ongoing investigation.

Vagal Nerve Stimulation (VNS)

Vagal nerve stimulation (VNS) is an emerging neuromodulatory approach with potential relevance to nicotine dependence through its effects on autonomic regulation and neurocircuitry implicated in addiction. Chronic tobacco use has been associated with alterations in vagal tone and heart rate variability, both of which are linked to stress reactivity, craving, and relapse risk. VNS is hypothesized to modulate these pathways by influencing central neurotransmission, and by promoting neuroregulatory and anti-inflammatory effects. VNS may influence stress, autonomic regulation, and neural pathways involved in craving and relapse. Although implantable VNS devices are FDA-approved for conditions such as epilepsy and treatment-resistant depression, newer noninvasive, portable devices are expanding the feasibility for broader clinical applications.^50,51 Although VNS has demonstrated biologic plausibility and potential relevance across several substance use disorders, smoking cessation-specific clinical evidence remains sparse. To date, evidence consists primarily of mechanistic studies and extrapolation from other addiction populations. However, interest in this approach is growing, and an NIH-funded exploratory clinical trial (R21CA302802) is currently evaluating non-invasive vagal nerve stimulation as an adjunct to nicotine replacement therapy for smoking cessation. ⁵² Larger controlled studies will be needed before routine clinical adoption.

EEG-Based Wearables and Neuroadaptive Behavioral Interventions

Electroencephalogram (EEG)-based wearable devices represent a novel intersection of digital therapeutics and neurofeedback, capable of delivering adaptive behavioral interventions in real time based on detected brain activity patterns. These devices, often configured as headband-style sensors, can guide users through brief cognitive behavioral therapy (CBT) or mindfulness-based exercises aimed at reducing stress and enhancing self-regulation, key drivers of smoking behavior and relapse. In early pilot studies, regular use over several weeks has been associated with statistically significant reductions in perceived stress, along with improvements in resilience, cognitive function, and quality of life.^53-55 Importantly, most of the current EEG-based wearable studies have evaluated stress reduction, mindfulness training, or symptom management in non-smoking populations rather than tobacco dependence specifically. While these findings highlight the potential role of neuroadaptive feedback in addressing the behavioral and affective components of nicotine dependence, current evidence remains limited to small, early-phase trials. As such, these technologies remain investigational and best used as adjunctive tools within a comprehensive cessation strategy.

Virtual Reality–Based Interventions

Virtual reality (VR)–based interventions offer an immersive platform for delivering behavioral therapy through simulated, controlled environments that replicate real-world smoking cues and high-risk situations. Grounded in principles of cue exposure therapy, VR allows for repeated, graded exposure to triggers while enabling patients to practice coping strategies in a safe and structured setting. Systematic reviews of VR interventions targeting health behaviors, including smoking, suggest potential benefits for both smoking cessation and reduction, with several studies demonstrating improved outcomes compared with minimal or standard behavioral support.^56,57 In addition to cue exposure, VR platforms may incorporate relaxation training, cognitive restructuring, and skills rehearsal, enhancing engagement and experiential learning. Despite these promising signals, most available studies remain small, heterogeneous, and frequently evaluate broader health-behavior outcomes rather than smoking cessation alone.^58-60 Consequently, heterogeneity in intervention design and the lack of large-scale RCTs limit definitive conclusions, and VR is best used as an adjunctive behavioral tool pending further evidence.

Integrative Perspective on Device-Based Therapies

Among device-based interventions, rTMS currently has the strongest clinical evidence and is the only modality with FDA clearance for smoking cessation. In contrast, VR-based interventions, EEG-guided wearables, and noninvasive VNS remain investigational and are supported primarily by pilot studies or small heterogeneous trials.^{13,14,27,48-51,53-56} At present, these approaches are not ready for routine primary care implementation, although they may help inform future adjunctive treatment strategies for patients with persistent nicotine dependence. Major limitations include limited availability, implementation variability, cost, and the lack of long-term outcome data.

Pharmacologic, behavioral, and device-based interventions address different components of nicotine dependence, supporting a multimodal approach that reflects the biologic and behavioral complexity of addiction.

Harm Reduction Strategies and Noncombustible Nicotine Products

For patients who do not achieve abstinence despite optimized treatment, alternative strategies such as harm reduction can be considered.^18,61,62 The increasing availability of e-cigarettes and other noncombustible nicotine products has complicated smoking cessation counseling in primary care.^13,18,62 While harm-reduction strategies may reduce toxicant exposure, current clinical guidelines continue to prioritize complete cessation with FDA-approved therapies as first-line treatment. Most of the health risk from tobacco use comes from combustion, which generates high levels of toxicants and carcinogens. Nevertheless, from a harm-reduction perspective, moving a patient from combustible cigarettes to noncombustible products may reduce exposure to those toxicants, even if nicotine use persists. Harm reduction does not eliminate risk, and counseling should address both potential reductions in exposure and ongoing uncertainties about long-term risks and the possibility of sustained nicotine dependence. In this context, smoking cessation (abstinence from combustible tobacco), nicotine abstinence, and harm reduction represent distinct but overlapping clinical goals. In practice, harm reduction is typically considered after adequate trials of evidence-based first-line therapies and is generally reserved for patients who are unable or unwilling to achieve abstinence after adequate trials of first-line therapies.

Current U.S. clinical guidelines do not recommend e-cigarettes as first-line smoking cessation therapies, and no e-cigarette product is FDA-approved for smoking cessation.

Although recent Cochrane reviews report high-certainty evidence that nicotine e-cigarettes can increase smoking cessation rates compared with some comparators, ¹⁵ the overall clinical evidence base remains more complex than efficacy outcomes alone. Concerns regarding product heterogeneity, long-term safety, dual use, regulatory status, and variability in real-world implementation continue to influence guideline recommendations and clinical adoption.^9,14,18 Systematic reviews focused on new nicotine products emphasize the need for robust study designs, clear definitions of quit motivation, adequate familiarization, and better compliance verification beyond self-report. Despite growing evidence, many clinical practice guidelines continue to prioritize approved pharmacotherapies and counseling as first-line treatment, reflecting safety concerns, product variability, and limited long-term outcome data.

Other harm-reduction strategies include extended use of approved NRT for patients who cannot discontinue conventional cigarette smoking immediately, structured reduction-to-quit approaches, and contingency-based support in selected settings. Some patients also use oral nicotine products (e.g., nicotine pouches). Nicotine pouches are tobacco-free oral nicotine products that deliver nicotine without combustion or aerosol generation. Although they likely expose users to substantially fewer toxicants than combustible cigarettes, evidence supporting their use as smoking cessation therapies remains limited.^63,64 Most available studies focus on toxicant exposure profiles, pharmacokinetics, product appeal, and patterns of use rather than long-term smoking abstinence outcomes.^63-66 Importantly, much of the available evidence regarding noncombustible nicotine products focuses on reductions in toxicant exposure rather than durable smoking cessation outcomes, and these endpoints should not be considered equivalent. Still, evidence supporting their use as cessation tools is sparse and often focuses on toxicant exposure rather than durable clinical outcomes. ⁶⁶ When discussing these products, clinicians should distinguish between complete abstinence from combustibles (i.e., conventional cigarettes) and a reduction in combustibles. This clarity helps avoid miscommunication in which “cutting down” is perceived as equivalent to meaningful risk reduction without changes in toxicant exposure or compensatory smoking.

Harm reduction also intersects with vaping cessation and dual-use management. Some patients, including young adults, seek to stop vaping nicotine; randomized trials of automated text-message programs have demonstrated efficacy for vaping cessation among young adult e-cigarette users. For dual users of conventional cigarettes and e-cigarettes, counseling must address both products and avoid unintended substitution of one harmful behavior for another. In primary care, the most defensible approach is to prioritize elimination of combustible exposure while supporting patients in reducing and ultimately discontinuing all nicotine when feasible. Although noncombustible nicotine products may reduce exposure to combustion-related toxicants, the long-term cardiopulmonary and vascular effects of sustained e-cigarette use remain uncertain. In addition, persistent dual use of combustible and noncombustible products may attenuate potential risk reduction and prolong nicotine dependence. In practice, follow-up should assess combustible and noncombustible product use, frequency of dual use, progression toward eliminating combustible exposure, nicotine dependence severity, adverse effects, quit readiness, and progress toward further nicotine reduction or eventual abstinence.

In primary care, harm reduction can be considered for selected patients, particularly those with repeated unsuccessful quit attempts or intolerance to first-line therapies. For patients who are unwilling or unable to quit combustible cigarettes despite optimized evidence-based therapy, clinicians may discuss switching to noncombustible products after failure or intolerance of evidence-based first-line therapies. A structured plan including clear goals, monitoring, and ongoing efforts toward eventual abstinence should be provided. Patients should be advised to avoid long-term dual use, and clinicians and practices should have a plan in place for monitoring, follow-up, and reassessment.

Special Populations

Important disparities persist in tobacco use prevalence, cessation success, and access to evidence-based treatment. Smoking rates remain disproportionately high among individuals with lower socioeconomic status, rural populations, sexual and gender minority groups, and persons with serious mental illness or substance use disorders. Structural barriers, including limited access to counseling, insurance coverage variability, prior authorization requirements, limited reimbursement for counseling, out-of-pocket costs for medications, transportation challenges, digital inequities, and targeted tobacco marketing, contribute to these disparities and limit treatment uptake and continuity. Primary care systems implementing smoking cessation interventions should prioritize equitable access, culturally responsive counseling, and flexible treatment delivery models.^67-69

Smoking prevalence remains substantially elevated among individuals with depression, schizophrenia spectrum disorders, and substance use disorders. These populations often experience higher nicotine dependence severity, greater relapse risk, and lower access to treatment. Nevertheless, evidence supports the effectiveness and safety of evidence-based pharmacotherapy and behavioral interventions in these populations when accompanied by close monitoring and integrated behavioral support.^70-73

In pregnant individuals, behavioral counseling remains the preferred first-line intervention because evidence supporting pharmacotherapy remains limited and safety data are less robust. Intensive counseling, motivational interviewing, pregnancy-specific quitline support, and repeated follow-up visits may improve cessation outcomes during pregnancy.^74,75 These disparities underscore the importance of equitable implementation strategies, culturally responsive counseling, and flexible treatment delivery models within primary care systems.

Implications for Primary Care Practice

PCCs and practices play a central role in identifying, initiating treatment for, and managing tobacco dependence over time. Integrating device-based therapies, digital tools, and harm-reduction strategies into routine practice can expand the reach of evidence-based interventions, especially for patients who do not respond to behavioral counseling and first-line pharmacotherapy. In practice, this means consistently delivering guideline-concordant care, including same-visit pharmacotherapy initiation and proactive behavioral support, with early follow-up to adjust treatment as needed, including extended duration pharmacotherapy or referral to more intensive services rather than repeated unsupported quit attempts.

Device-based and technology-enabled adjuncts are promising but should be reserved for patients with persistent dependence after adequate trials of established therapies, and clear goals, monitoring, and ongoing reassessment should guide their use. Harm reduction may be appropriate for those unable or unwilling to achieve abstinence, but should be approached as a secondary strategy, accompanied by structured plans to avoid long-term dual use and to support eventual cessation of all tobacco and nicotine products. Clinicians should educate patients on the distinctions between reducing combustible tobacco use and achieving meaningful risk reduction, as well as the limitations and uncertainties associated with noncombustible products.

Embedding these interventions into routine primary care workflows through opt-out referral systems, digital support integration, and stepwise care escalation can help overcome barriers to treatment delivery and sustain engagement. Continued evaluation of new technologies and harm-reduction approaches in real-world primary care settings is needed to guide best practices as the landscape of nicotine products and cessation tools evolves. Established pharmacotherapy and behavioral counseling remain the standard of care. Digital and device-based approaches should generally be considered adjunctive or investigational depending on the evidence base (Table 3). Figure 1 provides a stepwise, chronic-care algorithm that is practical for primary care implementation.^9,14

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Table 3.

Evidence Status of Smoking Cessation Interventions

Intervention	Evidence strength	Guideline supported	Clinical status
Behavioral counseling + pharmacotherapy	High	Yes	Standard of care
Combination NRT	High	Yes	Standard of care
Varenicline	High	Yes	Standard of care
Bupropion SR	High	Yes	Standard of care
Digital CBT/text support	Moderate	Adjunctive	Emerging adjunct
rTMS	Moderate	Limited specialty role	Adjunctive/select use
E-cigarettes for cessation	Mixed	No	Harm-reduction option
VNS	Low/Preliminary	No	Investigational
EEG wearables	Low/Preliminary	No	Investigational
VR interventions	Low/Preliminary	No	Investigational

Device-based therapies and digital tools can improve access to cessation interventions, particularly in settings with limited access to TTSs or where referrals are not feasible. Digital support and opt-out referral systems can streamline workflows, allowing care teams to deliver guideline-concordant interventions more efficiently and reduce missed opportunities. Multimodal approaches, including harm reduction, offer flexibility for patients with complex needs, supporting individualized care and potentially improving outcomes among those not responsive to standard therapies. Integrating these interventions within routine visits for acute, chronic, or preventive care leverages established patient relationships and continuity of care.

PCC and practices will need to navigate likely challenges in adopting these approaches. Resource constraints, including limited time, staffing, and reimbursement, can make it difficult to deliver and follow up on smoking cessation interventions, particularly when clinicians must also address competing demands across acute, chronic, and preventive health needs. Access to device-based therapies and digital tools may be hindered by cost or patient digital literacy, potentially widening disparities if not implemented equitably. The availability of TTS or behavioral health support also varies widely, and cumbersome or delayed referral processes can reduce the effectiveness of stepped-care models. Economic pressures, such as productivity targets and reimbursement models, may deprioritize preventive interventions, such as smoking cessation, when urgent acute or chronic issues require immediate attention. Managing harm reduction also requires careful counseling and monitoring to avoid unintended consequences, such as long-term dual use or misunderstanding of risk reduction, which can be particularly challenging in brief primary care encounters. Yet, despite these considerations, expanding access to comprehensive tobacco treatment and cessation support through these approaches has the potential to reduce smoking prevalence and associated morbidity and mortality.

This narrative review highlights several strengths, such as digital tools, messaging programs, device-based therapies, and harm-reduction strategies, to support smoking cessation in primary care. However, there are important limitations. The evidence supporting some of these emerging approaches, including neuromodulation, digital therapeutics, and noncombustible nicotine products, is still evolving and often based on early-phase or short-term studies. Additionally, implementation in primary care is challenged by issues of accessibility, cost, and varying levels of patient engagement. The rapid evolution of nicotine products and digital tools may outpace current evidence and guideline recommendations, underscoring the need for ongoing evaluation in real-world settings. Despite these limitations, embedding proactive follow-up, opt-out referral systems, and prioritizing early pharmacotherapy initiation within routine workflows offers a practical way to increase the reach and sustainment of smoking cessation interventions. Continued research and adaptation will be essential to maximize the benefits of these strategies while addressing their inherent challenges.