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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5250_Библиотеки_им_академика_М_И_Перельмана.pdf
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gambling, the published articles are mainly clinical studies or case report studies
with single-digit sample sizes. According to a systematic review published in 2023,
only eight studies were included in the analysis [43]. Among them, there were only
three randomized controlled clinical studies, which also indicates that the quality of
the original research evidence needs to be improved. It is currently difcult to draw
conclusions about the effectiveness of rTMS intervention in gambling populations.
In addition to gambling addiction, there have been case reports of high-frequency
intervention on the left DLPFC, reducing the time spent watching pornographic
images in a man with compulsive sexual behavior disorder related to online porn
use and the gaming time in a patient with internet gaming disorder [44].
Relapse
Due to certain practical difculties in collecting relapse data, only a few studies have
reported data on relapse. Taking a systematic review published in 2024 as an example, about 10% of the studies reported results related to relapse [10]. In alcohol
research, three out of ve studies on alcohol use disorder reported that multiple sessions of rTMS could signicantly reduce alcohol consumption [10]. In studies on
nicotine, some also showed that rTMS intervention could reduce the amount of
smoking [22, 45, 46]. For instance, a study by Amiaz etal. showed that 10 sessions
of 10Hz intervention on the left DLPFC could reduce patients’ tobacco use, but this
effect did not last until 6months after the intervention [22]. The study by DinurKlein etal. further revealed that 10Hz intervention on the lateral PFC and insula
could reduce tobacco use, while the effect of 1Hz rTMS intervention was not signicant [46]. In the research on cocaine, marijuana, opioids, and methamphetamine,
only one to two studies reported relapse situations after the rTMS treatment [11], and
all found signicant differences between the real rTMS group and the sham group.
Overall, the intervention effect of rTMS on relapse is still unclear, especially for
illegal drugs, and the existing evidence is insufcient to draw conclusions. The
existing evidence mainly suggests that effective rTMS protocol to reduce alcohol
and nicotine use disorder mainly adopt high-frequency stimulation targeting the
frontal lobe/insula, which may provide a reference for further research.
Other Outcomes
Existing studies have also found that rTMS intervention has potential therapeutic
effects on cognition, emotion, and sleep quality in patients with addictive disorder. In
terms of cognition, for example, Min and colleagues used a continuous 20- session
iTBS protocol to target the left DLPFC, which signicantly improved the verbal
working memory of patients with methamphetamine use disorder, with the therapeutic effect still maintained during a follow-up 1year after the intervention [27]. Another
study using 1Hz low-frequency intervention on the left DLPFC suggested an improvement in the inhibitory control abilities of methamphetamine-dependent patients [31].
In terms of emotion and sleep, there are also studies indicating that rTMS has a certain
intervention effect on levels of depression and anxiety, as well as sleep quality. For
instance, studies by Su and Yuan have shown the ability to improve sleep quality and
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emotional levels in methamphetamine users [47, 27], while Tsai and colleagues’
research claimed that high-frequency stimulation of the left DLPFC could improve
the level of depression in heroin-dependent patients in methadone clinics [38].
Safety
Most studies report that the adverse effects of rTMS on patients with SUDs are
generally mild. For instance, a meta-analysis conducted by Gay etal. showed that
out of 34 rTMS studies, 33 reported the presence of adverse effects, but the most
common adverse effects were minor discomfort, headache, dizziness, or insomnia
[48]. Patients receive the rTMS stimulation generally tolerate the treatment well,
with few cases of discontinuation or withdrawal due to adverse reactions. Notably,
the induction of seizures is theoretically the most severe acute adverse effect of
rTMS intervention. Given the potential variety of drugs used by the patient population with SUDs, some may facilitate the risk of seizure induction, such as seizures
occurring post-detoxication in some alcohol-dependent individuals [49].
Nonetheless, considering the large number of subjects who have undergone rTMS
treatment since 1998 and the extremely low incidence of actual seizures, the academic community generally considers the risk of rTMS-induced seizures to be very
low. Some adverse effects in case reports are relatively rare such as the unusual
adverse reaction of nocturnal emission and wet dreams reported by Shen etal. in a
case of methamphetamine use [50]. A case report described an unusual incidence of
extreme thirst in a patient after treatment [51]. There is also a study reporting a case
where a patient subjectively described unusual self-limiting involuntary hand movements after treatment, but without clear positive neurological examination evidence
[52]. When rTMS studies are conducted with parameter settings that do not signicantly exceed existing research evidence or are implemented under standardized
operational guidance, the probability of serious adverse events is low. To ensure the
safety of implementation and individual compliance, adverse effects should be continuously monitored and recorded during the intervention process.
Treatment Regimen
RTMS intervention parameters encompass various elements such as stimulation frequency, intensity, location, and duration. The distinct combinations of these parameters signicantly inuence treatment outcomes [46, 53]. Research has also been
directed toward symptomatology and brain activity during stimulation, indicating
their impact on the eventual therapeutic efcacy. The majority of studies utilize a
stimulation intensity ranging from 90% to 120% RMT, while a few have experimented with an 80% intensity level [48]. To date, no consensus exists on the optimal
stimulation intensity. However, due to the signicant discomfort experienced by
some patients when employing intensities above 100% RMT, a number of studies
have implemented a strategy of gradually increasing the intensity for intervention
[24]. The duration of rTMS therapy spans from a single day to several weeks. In
terms of target selection for stimulation, the DLPFC has been the focus of most
research efforts [10]. A meta-analysis has separately evaluated the effects of excitatory parameters targeting the left DLPFC versus the right DLPFC on craving
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T. Chen et al.
reduction, revealing that excitatory stimulation of the left DLPFC signicantly
decreases cravings, whereas the right-sided intervention does not show signicant
differences from the control group [13]. A limited number of studies have explored
the treatment effect of inhibitory parameter stimulation of the left DLPFC, right
frontal lobe, or mPFC.For example, Yuan etal. demonstrated that 1Hz frequency
stimulation of the left frontal cortex markedly reduced cravings in drug-dependent
patients, with a positive association between the reduction in cravings and the
enhancement of response inhibition capabilities [31]. Regarding dTMS, studies
have predominantly concentrated on the insula, with concurrent stimulation of the
PFC, showing promising results in smoking cessation. Over an 18-week monitoring
period, the 4-week continuous quit rate for patients was 19.4%, compared to 8.7%
in the control group [23]. The application of dual-target approaches appears to be
more effective than single-target stimulation. Chen and colleagues conducted a
study indicating that the combination of rTMS targeting the mPFC and DLPFC
resulted in superior and faster craving intervention effects [24]. In conclusion, the
potential applications of rTMS in addiction treatment are vast, yet its efcacy is
subject to a multitude of intervention parameters. Future research should delve into
identifying the most effective rTMS parameter combinations to enhance therapeutic
outcomes and offer more tailored treatment plans for individuals with addiction.
Additionally, larger-scale, systematic studies are necessary to conrm the long-term
efcacy and safety of TMS in the treatment of addiction.
In the selection of rTMS targets for behavioral addictions, the DLPFC is the
primary focus, with a particular emphasis on the left side. One study reported an
intervention protocol for the bilateral SMA.When targeting the left dorsolateral
DLPFC, high-frequency (e.g., 10–15Hz) stimulation is predominantly used, and
after 1–20 sessions of intervention, it can to some extent reduce the craving for
gambling [54], and also improve scores on emotional scales, but reports on the
impact on gambling behavior are limited. Zack etal. also analyzed the effectiveness
of a single session of nontraditional intervention parameters—continuous thetaburst stimulation (cTBS)—on gambling populations [54], but this protocol did not
show a signicant difference from the control group in reducing cravings. Sauvaget
etal. chose another inhibitory parameter of 1Hz to intervene on the right DLPFC of
gambling patients, setting the intensity to 120%, and also found no evidence of
effective intervention [55]. This seems to suggest that high-frequency intervention
on the DLPFC brings greater clinical benets to gambling populations than lowfrequency parameters. However, it is still too early to draw conclusions. In TMS
research on behavioral addictions, very few studies have explored the role of interventions in deep brain areas such as the insula.
Clinical Recommendations
Based on the existing evidence, Table6.1 summarizes the current recommendations
for rTMS interventions targeting SUDs. The rTMS treatment guidelines published
by the International Federation of Clinical Neurophysiology in 2019 only classied
“high-frequency intervention on the left DLPFC to reduce tobacco cravings and
consumption” as a C-level recommendation (possibly effective), while other SUDs
6 Addictive Disorders
Table 6.1 TMS in addictive disorder
Clinical recommendations
Frequency
TMS
Unilateral
rTMS
Deep TMS (H4
coil)
Bilateral rTMS Unclear Unclear Unclear Unclear NA
Accelerated
rTMS
Priming TMS Unclear Unclear Unclear Unclear NA
Synchronized
TMS
iTBS Unclear Unclear Unclear Unclear NA
Accelerated
iTBS
Continuous
TBS
Bilateral TBS Unclear Unclear Unclear Unclear NA
MST Unclear Unclear Unclear Unclear NA
Abbreviations: rTMS repetitive transcranial magnetic stimulation, TMS transcranial magnetic
stimulation, DLPFC dorsolateral prefrontal cortex, PFC prefrontal cortex
a
Evidence-based guidelines established by a group of European expert mention Unilateral rTMS
as Level C (possible efcacy) only for cigarette craving and consumption but no other addiction type
b
Clinical Practice Guidelines developed by the Indian Psychiatric Society mention Unilateral
rTMS as low recommendation for smoking cessation but no other addiction type
Left DLPFC High
Bilateral lateral
PFC+insula
Unclear Unclear Unclear Unclear NA
Unclear Unclear Unclear Unclear NA
Unclear Unclear Unclear Unclear NA
Unclear Unclear Unclear Unclear NA
(Hz)
frequency
10 20 18 FDA
Length
(min)
Not
mentioned
Duration
(sessions)
Not
mentioned
Levels +
referencesTarget
a
Level C [56]
b
Low level
[57]
approved
[58]
155
were not included due to insufcient evidence [56]. In 2020, the FDA approved
rTMS (H4 deep coil) for the treatment of nicotine use disorder. In 2023, the Indian
Psychiatric Association again classied “high-frequency intervention on the left
DLPFC for the treatment of nicotine use disorder” as a low-level recommendation,
while other substance uses were not recommended due to limited evidence [57]. In
summary, based on the current research, the evidence for rTMS treatment of nicotine use disorder has gradually gained recognition, while there is still a lack of sufcient evidence to support the widespread clinical application for other SUDs.
6.2.1.2 Bilateral rTMS
Compared to unilateral rTMS intervention, bilateral rTMS intervention could
simultaneously stimulate both hemispheres of the brain, which may help to more
comprehensively activate brain regions associated with specic functions, thereby
improving therapeutic outcomes. Additionally, bilateral rTMS may contribute to
balancing the excitability of both cerebral hemispheres. Taking depression as an
example, previous studies have suggested that there is a functional imbalance
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T. Chen et al.
between the left and right DLPFC regions in patients with depression during the
emotional regulation process [59]. There are relatively few studies on bilateral
rTMS intervention in the eld of addiction. Wing etal. conducted a bilateral rTMS
study targeting patients with nicotine dependence comorbid schizophrenia. The
study applied a 20-Hz frequency rTMS to both DLPFC regions, and 20 sessions of
consecutive intervention signicantly reduced cravings [60]. Another study conducted by Kozak etal. used similar parameters but adjusted the number of intervention sessions to six and found no change in the craving levels of nicotine-dependent
patients [61]. Bidzinski etal. recently explored the efcacy of high-frequency bilateral DLPFC stimulation on patients with schizophrenia comorbid cannabis use disorder, nding that it could reduce PANSS scores but had limited impact on cannabis
craving scores [62].
Despite limited research, existing studies still suggest the safety prole of bilateral rTMS intervention on addictive disorder. Overall, no studies have reported
severe adverse effects. The adverse reactions are similar to those of unilateral rTMS
intervention, mostly manifesting as headaches, neck pain, dizziness, and so on, and
are generally mild, without signicantly affecting treatment participation [62].
Current research on bilateral rTMS intervention has focused on bilateral DLPFC
(i.e., studies that specically used gure-eight coils or other non-deep coils), and all
have used high-frequency parameters (10–20Hz) with a treatment intensity of
90–100% rMT.Unlike ndings in depression, there is currently no concrete evidence to suggest an hemispheres imbalance in populations with addictive disorder.
However, some studies suggest that there may be weakened connections between
the two cerebral hemispheres, thus promoting the strength of both hemispheres
could be a direction for intervention. In individuals with internet addiction, weakened functional connectivity between different brain regions has been observed
[63]. Additionally, there are many possibilities for bilateral rTMS intervention, such
as the above studies that seem to nd that low-frequency intervention on the right
DLPFC can reduce cravings [64], while conventional high-frequency parameter
intervention on the left DLPFC can achieve the similar therapeutic goal [27].
Furthermore, the collaboration between different brain regions in the two hemispheres may also be a direction for future development of bilateral interventions.
For instance, Serenella etal. found abnormal connectivity in bilateral regions such
as the putamen, caudate nucleus, and middle frontal gyrus [65]. In fact, an increasing number of studies highlight the signicant role of interregional network activity
in addictive disorder and other cognitive activities. Compared to unilateral interventions, bilateral interventions are expected to further leverage the advantages of
rTMS.However, due to the limited number of published studies and sample sizes all
below 30 participants, it is still difcult to draw conclusions about the efcacy of
interventions targeting both brain hemispheres.
6.2.1.3 Accelerated rTMS
While rTMS has shown signicant therapeutic effects in the treatment of some
mental and psychological disorders, it has also been constrained by a slow response
time. For patients with acute episodes and urgent treatment demands, the rapid
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onset of treatment is an important factor for clinicians to determine whether a therapy is suitable for practical clinical work. On the other hand, it appears that an
increase in the total number of stimulation pulses is correlated with the nal therapeutic outcome. Accelerated rTMS protocols have been developed in response to
such needs. In 2022, a renowned accelerated protocol—Stanford Accelerated
Intelligent Neuromodulation Therapy (SAINT)—received FDA approval for the
treatment of treatment-resistant depression, with remission rates (78.6–90.5%) signicantly higher than the 33% of conventional rTMS [66, 67]. There is a scarcity of
research on accelerated interventions in the eld of addiction. For instance, in a
study by Wu and colleagues, after 15 sessions of accelerated high-frequency rTMS
treatment, 13 out of 22 alcohol-dependent patients relapsed within 4weeks [68].
Interestingly, compared to those who abstained, relapsers exhibited a greater reduction in brain gray matter volume. In another study, 15 consecutive sessions targeting
the right DLPFC signicantly reduced psychological cravings in alcohol-dependent
patients, although cue-induced cravings did not change signicantly [69].
Although accelerated rTMS therapy appears to demonstrate stronger therapeutic
effects in various mental disorders, accelerated protocols may induce additional
adverse effect and risks. Therefore, it is important to monitor changes in cortical
excitability and subjective discomfort reported by patients as the number of pulses
increases. Although one of the serious risks of TMS, seizure, is relatively low, but
due to the increase in the number of stimulation pulses, EEG monitoring during the
stimulation process may have certain clinical signicance [70].
Given the limited research and only one accelerated rTMS study suggesting a
reduction in cravings for alcohol-dependent patients [69], further evidence is needed
to conrm the effects of accelerated rTMS, making it difcult to recommend for
clinical use at this time.
6.2.2 Deep TMS
Traditional gure-eight coils can typically stimulate depths of about 0.8cm beneath
the scalp, while dTMS can stimulate depths of up to 4cm beneath the scalp surface
[71], with the specic stimulated location being related to the coil model. Currently,
there are over 20 types of H-shape dTMS coils [72]. In addiction research, researchers mainly apply H coils to stimulate bilateral DLPFC, mPFC, ACC, and insular
regions [10]. The stimulation intensity is set between 80% and 120% rMT. The
number of sessions ranges from 10 to 20. Studies focus on cocaine, tobacco, and
alcohol use disorders, with one study conducted on gambling addiction [40].
Using dTMS coils to stimulate traditional targets such as the DLPFC for multiple
consecutive interventions can signicantly reduce cravings and depressive symptoms in alcohol-dependent patients (after 20 sessions) and also decrease relapse
rates in cocaine-dependent patients (after 12 sessions) [73, 74]. When using the H7
coil for high-frequency intervention on the mPFC and dorsal ACC regions, it can
signicantly reduce cocaine intake [34]. The choice of frequency may also affect
the outcome. For instance, Dinur-Klein etal.’s study further revealed that 10Hz
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T. Chen et al.
intervention on the lateral PFC and insula can reduce tobacco use, while the effect
of 1Hz intervention is not signicant [46]. However, the sample sizes of the above
studies are small. Due to the variety of coil types, the number of articles published
for different coil is limited, and the intervention sites for dTMS coils are not consistent, it is difcult to form a unied conclusion. For example, Harel etal. applied the
H7 coil to stimulate the mPFC and ACC [14], while Perini et al. targeted the
insula [15].
A large-sample, multicenter study has strengthened condence in dTMS treatment for addiction. This work used the H4 deep coil to stimulate bilateral lateral
PFC and insula, and a continuous 6-week intervention showed good effects on
reducing cravings [23]. Importantly, the protocol not only reduced psychological
cravings but also showed good effects in quitting smoking. It resulted in a 4-week
continuous quit rate of 19.4% (compared to 8.7% in the control group) during an
18-week follow-up [23]. It is known that compared to traditional rTMS interventions, dTMS have the potential to directly target deep brain regions associated with
reward, such as the insula, VTA, and nucleus accumbens, which are often considered closely related to addiction [6].
The potential adverse reactions of dTMS in addiction are very similar to other
rTMS intervention protocols. Zangen etal. provided a detailed report [23]. In their
study, the most common adverse reaction was headache. Additionally, pain at the
stimulation site, face, jaw, neck, and muscle spasms/twitches may occur. The pain
level is mild to moderate and disappears after treatment, which is similar to other
type of rTMS interventions [75].
There is currently a limited amount of evidence that can form recommendations
and the studies are distributed across different addictive substances. Among them,
Zangen etal.’s work [23], due to its large sample size and long-term follow-up evidence, has prompted the FDA to approve dTMS (H4 deep coil) for the treatment of
nicotine addiction in 2020. As for other types of substance dependence, it is difcult
to form conclusive recommendations recently.
6.2.3 Priming TMS
To optimize the therapeutic effects and advantages of TMS stimulation, researchers
are continuously exploring potential new intervention parameters and protocols.
Among them, pTMS has shown certain potential. The typical PpTMS protocol is
designed to optimize the subsequent main rTMS therapeutic effects. These protocols adjust the excitability state of the cerebral cortex in advance to enhance or alter
the response to subsequent treatments. Common priming rTMS protocols include
high-frequency rTMS priming and low-frequency rTMS priming strategies [76].
Previous studies on priming rTMS have mainly focused on patients with major
depressive disorder. For example, in a study by Fitzgerald etal. [77], compared to
the use of low-frequency rTMS intervention alone, applying 6Hz high-frequency
rTMS priming followed by 1Hz rTMS stimulation of the right DLPFC showed a
stronger antidepressant effect. The mechanism of priming rTMS is not yet clear, but
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it is generally believed to be related to the following mechanisms: changing the
excitability level of the cerebral cortex to regulate neural plasticity [76]. The therapeutic effect of priming rTMS on addiction is not yet clear. The author searched
databases such as PubMed and CNKI and found no published clinical trials.
Consistent with other mental disorders, one of the important pathogenic mechanisms of addictive disorder lies in the impaired plasticity of brain regions [78]. This
also implies that priming rTMS may have certain therapeutic potential for addictive
disorder.
6.2.4 Synchronized TMS
Synchronized transcranial magnetic stimulation (sTMS) is a specic form of
rTMS.This stimulation protocol emphasizes synchronization with brain activity or
other stimuli in time or space. The design concept of sTMS is to enhance the effectiveness and specicity of stimulation by more precisely matching the natural
rhythms of the brain or neural activity patterns in specic task states. In terms of
integration with measurement tools, sTMS can be designed to synchronize with the
rhythms of electroencephalographic (EEG) activity (such as alpha frequency) and
can also be combined with specic cognitive-psychological tasks. sTMS emphasizes the individualization of each subject, resulting in signicant differences in
protocol design across various studies.
Taking depression as an example, studies have indicated that the power of left
hemisphere alpha oscillations is signicantly increased [79] and positively correlated with depressive symptoms [80]. A decrease in alpha power has also been
found to reect a good response to antidepressant treatment [81]. To enhance the
treatment effect of depression, Zrenner and colleagues developed a new intervention strategy—rTMS triggered at the negative EEG peak of instantaneous alpha
oscillations. It was found that a single session of alpha sTMS could signicantly
reduce EEG resting-state alpha activity in the left DLPFC region [82], with no signicant changes observed in the control group. Continuous low-eld magnetic stimulation synchronized to an individual’s alpha frequency (IAF) for 6weeks showed
more signicant improvement in depressive symptoms compared to the control
group [83]. However, several studies concluded that the alpha sTMS protocol did
not signicantly outperform the control in improving depressive symptoms in
patients with depression [84, 85].
In addiction area, there is currently a lack of rTMS intervention protocols synchronized with specic EEG activity. A study protocol published in 2023 plans to
conduct low-eld stimulation synchronized to an individual’s alpha peak frequency
among retired military subjects with addiction disorders, but the results have not yet
been announced [86]. In addition to synchronizing with EEG activity, synchronizing specic states during the rTMS intervention process seems to further enhance
the effectiveness of addiction intervention. Dinur-Klein used a high-frequency stimulation protocol targeting bilateral PFC and insula combined with smoking cue
exposure to enhance the reduction in cigarette consumption, increasing the quit rate
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to 44% [46]. Another study compared the therapeutic effects of 10Hz intervention
on DLPFC synchronized with smoking video cue exposure versus sham stimulation
synchronized with cue exposure [87], suggesting the role of 10Hz intervention in
reducing smoking consumption. Synchronized TMS protocols are theoretically
appealing. However, there is currently a lack of clear evidence, indicating superiority over traditional intervention strategies on additive disorder.
6.2.5 TBS
6.2.5.1 iTBS
Efficacy
Intermittent theta burst stimulation (iTBS) is a variant of rTMS. iTBS is generally
believed to excite the brain activities. By mimicking the brain’s natural activity patterns, iTBS enhances therapeutic effects with short bursts of high-frequency stimulation. iTBS is typically set to deliver three burst pulses every 200 ms, with an
intra-burst frequency of 50Hz, and this pattern is applied for 2s followed by an 8-s
interval [88]. The mechanism of iTBS involves changes in synaptic plasticity [89],
i.e., by regulating the activity of certain excitatory or inhibitory neurotransmitter
receptors, which in turn induce long-term potentiation (LTP) or long-term depression (LTD)-like effects. Additionally, TBS can regulate gene expression and protein
synthesis [90]. In clinical applications, due to its short stimulation time and low
stimulation intensity, iTBS has been widely used to treat neurological and psychiatric disorders such as depression and ischemic stroke, showing good efcacy and
safety [56]. A multicenter clinical trial found that iTBS stimulation of the DLPFC
has comparable antidepressant efcacy to 10Hz rTMS, leading to FDA approval for
the treatment of treatment-resistant depression [91]. Exploration of iTBS in addiction disorders has mainly focused on populations with methamphetamine use disorder [24, 27, 92–95]. Additionally, a small number of studies have been conducted in
nicotine, cocaine, and heroin use disorders [96–100]. In studies reporting cravings
outcome, almost all studies found that iTBS intervention on the left DLPFC signicantly reduced psychological cravings in methamphetamine use disorder. Moreover,
under the premise of shorter treatment duration, the iTBS protocol is not inferior to
the 10Hz classical protocol [92]. Chen etal.’s study showed that iTBS intervention
targeting the left DLPFC reduced patients’ attention bias toward drugs, which was
signicantly related to changes in cravings [101]. Additionally, iTBS targeting the
left DLPFC also showed improvements in working memory [27]. In previous studies, impaired working memory was found to be one of the most common cognitive
impairments in methamphetamine use disorder [102]. Although the sample sizes of
the above studies are small and larger randomized controlled studies are needed to
conrm the observations, iTBS appears to be an effective method that better meets
clinical needs, especially considering the difference between its short duration
(3min) and that of high-frequency stimulation (often more than 10min). Reducing
treatment duration helps to decrease patient discomfort and is expected to reduce
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dropout rates while ensuring treatment effectiveness. In populations with nicotine
and heroin use disorder, iTBS intervention on the PFC has also been found to reduce
psychological cravings [98, 100]. These consistent results seem to indicate the
strong potential of the iTBS intervention protocol in reducing cravings in populations with addictive disorder. Other indicators, due to the high heterogeneity of
studies, are still difcult to conclude.
Safety
One of the advantages of the TBS protocol is its relatively short intervention time,
which may reduce the discomfort associated with longer durations of rTMS interventions. In studies regarding iTBS intervention, the main adverse reactions reported
are mild scalp discomfort, temporary headaches, dizziness, and nausea, all of which
improve after the treatment is discontinued. No studies have reported severe adverse
reactions such as seizures. These adverse reactions are similar to those observed
with other TMS intervention protocols. In fact, due to the lack of dedicated comparative studies, it is currently difcult to determine which intervention strategy has
more prominent adverse reactions.
Treatment Regimen
In addiction treatment, iTBS intervention protocols often target the left DLPFC,
with a minority of studies stimulating the bilateral DLPFC or the right inferior frontal gyrus [99, 100]. The intensity of stimulation is between 80–100% rMT.The
majority of studies have focused on changes in psychological cravings, with a
smaller portion addressing relapse and cognitive changes. In terms of psychological
cravings, iTBS intervention targeting the left DLPFC has been found to signicantly improve patients’ levels of psychological cravings. However, there is only
one study that conducted iTBS intervention on the right side, and although this
study also suggested a signicant reduction in psychological cravings [103]. It is
noteworthy that relapse, a key behavioral observation indicator in addiction treatment, is rarely reported. Su etal. followed up with methamphetamine-dependent
patients after 20 consecutive iTBS interventions and found no signicant difference
in relapse rates compared to the control group [27].
Clinical Recommendations
Synthesizing the current application exploration of iTBS intervention protocols in
populations with addictive disorder, it seems meaningful that iTBS stimulation of
the left DLPFC could reduce psychological cravings; however, further large sample
randomized controlled clinical trial need to be conducted. There is currently a lack
of more substantial research evidence to recommend improvements in other clinical
indicators.
6.2.5.2 Accelerated iTBS
Based on the potential demonstrated by iTBS intervention protocols, to meet the
needs of more urgent disease conditions (such as suicide), researchers have explored
the role and safety of accelerated iTBS intervention protocols. Accelerated iTBS