Trial Summary
What is the purpose of this trial?The goal of this clinical trial is to compare two active types of transcranial magnetic stimulation in two nicotine-using populations: nicotine-using people with psychosis and nicotine-using people without a diagnosis of a psychotic disorder. The main questions it aims to answer are:
1. Can rTMS change functional connectivity in brain circuits associated with nicotine use?
2. Are those rTMS-induced changes in functional connectivity related to craving?
Participants will complete tasks assessing their cognitive performance and craving before and after each week of TMS. Researchers will compare the effect of each TMS intervention on participants with and without psychosis to see if one type of TMS has an effect on nicotine craving.
What data supports the idea that Brain Stimulation for Nicotine Addiction in Schizophrenia is an effective treatment?The available research shows that brain stimulation, specifically repetitive transcranial magnetic stimulation (rTMS), may help reduce tobacco cravings and consumption in people with schizophrenia. One study found that rTMS decreased tobacco consumption and craving in people with schizophrenia. Another study showed that rTMS led to a higher quit rate in smokers compared to a fake treatment, with 19.4% of participants quitting smoking after real rTMS compared to 8.7% after the fake treatment. However, results are mixed, and more research is needed to confirm its effectiveness specifically for people with schizophrenia.25678
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you must stop taking your current medications. However, your medications will be reviewed by a physician, and a decision will be made based on your medical history and medication details. Any recent changes in medications or hospitalizations within the past 90 days may affect your eligibility.
Is the treatment Network-Targeted Neuromodulation effective for helping people with schizophrenia quit smoking?Yes, Network-Targeted Neuromodulation, also known as repetitive transcranial magnetic stimulation (rTMS), shows promise in helping people with schizophrenia reduce cigarette cravings and consumption. Studies suggest it can decrease tobacco use and cravings by stimulating specific brain areas, making it a promising treatment for smoking cessation.12356
What safety data exists for brain stimulation treatment for nicotine addiction in schizophrenia?The safety of repetitive transcranial magnetic stimulation (rTMS) for nicotine addiction has been evaluated in several studies. A multicenter double-blind randomized controlled trial involving 262 chronic smokers demonstrated that rTMS is a safe treatment protocol for smoking cessation, leading to FDA clearance for this use. Additionally, a study on high-dose rTMS in schizophrenia patients with refractory negative symptoms evaluated its safety, although specific safety outcomes were not detailed in the abstract. Overall, rTMS is considered a non-invasive and safe method for treating psychiatric disorders and addictions, including nicotine dependence.24568
Eligibility Criteria
This trial is for individuals who use nicotine and have schizophrenia, as well as those without a psychotic disorder. Participants should be interested in how brain stimulation might help with nicotine cravings.Treatment Details
The study tests two types of transcranial magnetic stimulation (rTMS) to see if they can alter brain activity related to nicotine use and reduce cravings. It compares the effects on people with and without psychosis.
2Treatment groups
Active Control
Group I: L DLPFC-Targeted iTBS, Then DMN-Targeted cTBSActive Control1 Intervention
Participants will first receive intermittent theta burst stimulation (iTBS) at 100% active motor threshold (AMT) anatomically targeted to the left dorsolateral prefrontal cortex for five consecutive days. iTBS will be administered in a pattern consisting of 2s trains of 3 pulses at 50Hz, repeated at 5Hz, every 10s for a total of 600 pulses. There will then be a washout period of at least two weeks before starting the DMN-Targeted cTBS. Participants will then receive continuous theta burst stimulation (cTBS) at 100% AMT targeted to an individual-specific map of the left parietal node of the default mode network for five consecutive days. cTBS will be administered in a pattern consisting of 1 60s train of 3 pulses at 50Hz, repeated at 5Hz, for a total of 600 pulses.
Group II: DMN-Targeted cTBS, Then L DLPFC-Targeted iTBSActive Control1 Intervention
Participants will first receive continuous theta burst stimulation (cTBS) at 100% AMT targeted to an individual-specific map of the left parietal node of the default mode network for five consecutive days. cTBS will be administered in a pattern consisting of 1 60s train of 3 pulses at 50Hz, repeated at 5Hz, for a total of 600 pulses. There will then be a washout period of at least two weeks before starting the L DLPFC-Targeted iTBS. Participants will receive intermittent theta burst stimulation (iTBS) at 100% active motor threshold (AMT) anatomically targeted to the left dorsolateral prefrontal cortex for five consecutive days. iTBS will be administered in a pattern consisting of 2s trains of 3 pulses at 50Hz, repeated at 5Hz, every 10s for a total of 600 pulses.
Network-Targeted Neuromodulation is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Transcranial Magnetic Stimulation for:
- Smoking cessation
- Major depressive disorder
- Obsessive-compulsive disorder
🇪🇺 Approved in European Union as Transcranial Magnetic Stimulation for:
- Major depressive disorder
- Obsessive-compulsive disorder
- Smoking cessation
🇨🇦 Approved in Canada as Transcranial Magnetic Stimulation for:
- Major depressive disorder
- Obsessive-compulsive disorder
- Smoking cessation
Find a clinic near you
Research locations nearbySelect from list below to view details:
Vanderbilt University Medical CenterNashville, TN
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Who is running the clinical trial?
Vanderbilt University Medical CenterLead Sponsor
References
Repeated high-frequency transcranial magnetic stimulation over the dorsolateral prefrontal cortex reduces cigarette craving and consumption. [2022]To evaluate the effect of repeated high-frequency transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC), combined with either smoking or neutral cues, on cigarette consumption, dependence and craving.
Repetitive transcranial magnetic stimulation reduces cigarette consumption in schizophrenia patients. [2017]High-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) seemed to decrease tobacco consumption and craving in nicotine-dependent people without psychiatric disorder or otherwise healthy people. Even if the prevalence of cigarette smoking in schizophrenia patients is high and estimated to be between 45% and 88%, this technique has not been systematically studied in this indication in schizophrenia yet.
Transcranial Magnetic Stimulation Combined With Nicotine Replacement Therapy for Smoking Cessation: A Randomized Controlled Trial. [2018]Further evidence suggests that repetitive Transcranial Magnetic Stimulation (rTMS) is an effective method to reduce tobacco craving among smokers.
[Effectiveness and safety of high dose transcranial magnetic stimulation in schizophrenia with refractory negative symptoms: a randomized controlled study]. [2018]To evaluate the efficacy and safety of high dose transcranial magnetic stimulation (rTMS) in patients with schizophrenia with refractory negative symptoms.
Effects of short-term, high-frequency repetitive transcranial magnetic stimulation to bilateral dorsolateral prefrontal cortex on smoking behavior and cognition in patients with schizophrenia and non-psychiatric controls. [2021]High rates of tobacco smoking and smoking cessation failure in schizophrenia may be related to prefrontal cortical dysfunction. Novel treatment options for tobacco use disorder are needed given the limited efficacy of current pharmacotherapies. Preliminary evidence suggests high-frequency repetitive transcranial magnetic stimulation (rTMS) to bilateral dorsolateral prefrontal cortex (DLPFC) may suppress tobacco craving in smokers with schizophrenia. The goal of this study was to determine effects of rTMS for tobacco craving and cognition using a short-term (3-day) human laboratory paradigm.
Repetitive transcranial magnetic stimulation for smoking cessation: a pivotal multicenter double-blind randomized controlled trial. [2021]Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation method increasingly used to treat psychiatric disorders, primarily depression. Initial studies suggest that rTMS may help to treat addictions, but evaluation in multicenter randomized controlled trials (RCTs) is needed. We conducted a multicenter double-blind RCT in 262 chronic smokers meeting DSM-5 criteria for tobacco use disorder, who had made at least one prior failed attempt to quit, with 68% having made at least three failed attempts. They received three weeks of daily bilat-eral active or sham rTMS to the lateral prefrontal and insular cortices, followed by once weekly rTMS for three weeks. Each rTMS session was administered following a cue-induced craving procedure, and participants were monitored for a total of six weeks. Those in abstinence were monitored for additional 12 weeks. The primary outcome measure was the four-week continuous quit rate (CQR) until Week 18 in the intent-to-treat efficacy set, as determined by daily smoking diaries and verified by urine cotinine measures. The trial was registered at ClinicalTrials.gov (NCT02126124). In the intent-to-treat analysis set (N=234), the CQR until Week 18 was 19.4% following active and 8.7% following sham rTMS (X2 =5.655, p=0.017). Among completers (N=169), the CQR until Week 18 was 28.0% and 11.7%, respectively (X2 =7.219, p=0.007). The reduction in cigarette consumption and craving was significantly greater in the active than the sham group as early as two weeks into treatment. This study establishes a safe treatment protocol that promotes smoking cessation by stimulating relevant brain circuits. It represents the first large multicenter RCT of brain stimulation in addiction medicine, and has led to the first clearance by the US Food and Drug Administration for rTMS as an aid in smok-ing cessation for adults.
Investigating repetitive transcranial magnetic stimulation on cannabis use and cognition in people with schizophrenia. [2022]Cannabis use disorder (CUD) occurs at high rates in schizophrenia, which negatively impacts its clinical prognosis. These patients have greater difficulty quitting cannabis which may reflect putative deficits in the dorsolateral prefrontal cortex (DLPFC), a potential target for treatment development. We examined the effects of active versus sham high-frequency (20-Hz) repetitive transcranial magnetic stimulation (rTMS) on cannabis use in outpatients with schizophrenia and CUD. Secondary outcomes included cannabis craving/withdrawal, psychiatric symptoms, cognition and tobacco use. Twenty-four outpatients with schizophrenia and CUD were enrolled in a preliminary double-blind, sham-controlled randomized trial. Nineteen participants were randomized to receive active (n = 9) or sham (n = 10) rTMS (20-Hz) applied bilaterally to the DLPFC 5x/week for 4 weeks. Cannabis use was monitored twice weekly. A cognitive battery was administered pre- and post-treatment. rTMS was safe and well-tolerated with high treatment retention (~90%). Contrast estimates suggested greater reduction in self-reported cannabis use (measured in grams/day) in the active versus sham group (Estimate = 0.33, p = 0.21; Cohen's d = 0.72), suggesting a clinically relevant effect of rTMS. A trend toward greater reduction in craving (Estimate = 3.92, p = 0.06), and significant reductions in PANSS positive (Estimate = 2.42, p = 0.02) and total (Estimate = 5.03, p = 0.02) symptom scores were found in the active versus sham group. Active rTMS also improved attention (Estimate = 6.58, p
Noninvasive Brain Stimulation for Nicotine Dependence in Schizophrenia: A Mini Review. [2022]Individuals with schizophrenia are 10 times more likely to have a tobacco use disorder than the general population. Up to 80% of those with schizophrenia smoke tobacco regularly, a prevalence three-times that of the general population. Despite the striking prevalence of tobacco use in schizophrenia, current treatments are not tailored to the pathophysiology of this population. There is growing support for use of noninvasive brain stimulation (NIBS) to treat substance use disorders (SUDs), particularly for tobacco use in neurotypical smokers. NIBS interventions targeting the dorsolateral prefrontal cortex have been effective for nicotine dependence in control populations-so much so that transcranial magnetic stimulation is now FDA-approved for smoking cessation. However, this has not borne out in the studies using this approach in schizophrenia. We performed a literature search to identify articles using NIBS for the treatment of nicotine dependence in people with schizophrenia, which identified six studies. These studies yielded mixed results. Is it possible that nicotine has a unique effect in schizophrenia that is different than its effect in neurotypical smokers? Individuals with schizophrenia may receive additional benefit from nicotine's pro-cognitive effects than control populations and may use nicotine to improve brain network abnormalities from their illness. Therefore, clinical trials of NIBS interventions should test a schizophrenia-specific target for smoking cessation. We propose a generalized approach whereby schizophrenia-specific brain circuitry related to SUDs is be identified and then targeted with NIBS interventions.