Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5250_Библиотеки_им_академика_М_И_Перельмана.pdf
11 Post-traumatic Stress Disorder
305
undergo careful evaluation prior to receiving AITBS treatment. Additionally, the
long-term safety and efcacy of AITBS for PTSD remain undetermined and require
further study.
Treatment Regimen
The AITBS treatment regimen for PTSD generally involves delivering brief bursts
of high-frequency magnetic pulses to the right DLPFC or bilateral DLPFC, utilizing
TMS to induce synaptic plasticity, which may contribute to symptom alleviation [59].
Treatment protocols vary according to symptom severity and individual response.
However, a typical regimen consists of daily sessions over 10–15days, each lasting
3–10 min. The stimulation follows a theta-burst pattern, with bursts of 50 Hz
repeated at 5Hz (with a 200ms interval between bursts).
The intensity of the magnetic pulses is usually calibrated to the motor threshold,
sufcient to induce a muscle twitch in the contralateral hand or forearm, ensuring
adequate stimulation of neural activity in the targeted brain region.
Unlike conventional TMS, AITBS employs the theta-burst pattern, which is
believed to induce synaptic plasticity more effectively, potentially enhancing its
therapeutic efcacy for PTSD.
Clinical Recommendations
AITBS offers a promising treatment alternative for individuals with PTSD, with
preliminary evidence indicating its potential efcacy in reducing symptoms and
demonstrating good tolerability. However, further research is required to establish
its safety and effectiveness in larger, more diverse patient populations and to explore
the underlying neurobiological mechanisms responsible for its effects.
11.2.5.3 Bilateral TBS
Efficacy
Early studies have examined the efcacy of bilateral TBS in mitigating PTSD
symptoms [60]. Bilateral sequential TBS has been shown to effectively alleviate
post-traumatic stress and associated depressive symptoms [64]. Additionally, several studies have reported improvements in both depression and PTSD symptoms
following TBS treatment, with bilateral stimulation potentially yielding more substantial responses compared to single-site stimulation [65]. These ndings suggest
that bilateral TBS could be a viable treatment strategy for individuals with comorbid PTSD and MDD.
Safety
The safety of bilateral TBS for PTSD has been evaluated in multiple studies, with
preliminary evidence indicating that TBS is relatively safe, causing minimal side
effects such as mild headaches and discomfort at the stimulation site [60, 64].
While these ndings are encouraging, further research is necessary to fully
assess the potential risks and long-term effects of TBS.Additionally, individual
306
S. Sha et al.
variations in tolerability, as well as contraindications such as the presence of metallic implants or certain medical conditions, should be carefully considered.
Treatment Regimen
The optimal treatment regimen for bilateral TBS in PTSD remains an area of active
investigation. The bilateral sequential TBS protocol typically consists of 67 iTBS
trains, delivered to each hemisphere at 8-s intervals. Treatment is administered
5days per week for 2weeks, totaling 10 sessions. The TBS protocol involves delivering 20 columns of stimulation at 5Hz, each containing three 50Hz pulses repeated
at 5Hz. Previous studies have reported a treatment schedule consisting of 5 consecutive treatment days followed by 2days of rest, extending over a 3-week period
[60, 64].
The choice of treatment regimen may vary depending on factors such as the
severity of PTSD symptoms, comorbid conditions, and patient preferences. Thus, it
is crucial for clinicians to tailor treatment plans to the individual, closely monitoring
patient response and tolerability.
Clinical Recommendations
Bilateral theta-burst stimulation holds signicant promise as a therapeutic option
for individuals with PTSD, particularly those with comorbid MDD.Preliminary
evidence supports its effectiveness in alleviating PTSD symptoms, with good tolerability and minimal side effects. However, additional research is needed to better
understand the optimal treatment regimen, assess potential risks, and evaluate the
long-term effects of this innovative treatment modality.
11.2.6 MST
Magnetic seizure therapy (MST) is an emerging noninvasive brain stimulation technique that utilizes high-intensity TMS to induce a generalized seizure under anesthesia. Derived from electroconvulsive therapy (ECT), MST differs in several
signicant ways. Unlike ECT, which targets deeper brain structures, MST focuses
on more localized brain regions and induces seizures in the supercial cortical layers, potentially reducing the impact on deeper structures such as the hippocampus
[66, 67]. Additionally, MST employs pulsed magnetic elds, while ECT uses electric currents. Although both therapies are effective in treating severe psychiatric
disorders, MST is generally regarded as safer, with fewer cognitive and memory
side effects, whereas ECT may cause transient cognitive impairments but remains
highly effective in a broader range of conditions. Both treatments have shown efcacy in treating severe depressive disorder and other psychiatric conditions, with
MST being a newer and less explored option compared to ECT.The choice between
the two treatments should be informed by individual patient factors and preferences,
in consultation with a qualied psychiatrist [20].
11 Post-traumatic Stress Disorder
307
11.2.6.1 Efficacy
Although MST has demonstrated potential in treating a variety of psychiatric disorders, including MDD and schizophrenia, its effectiveness in treating PTSD has not
been extensively researched. However, the underlying mechanisms by which MST
induces neural plasticity and alters resting-state functional connectivity suggest that
it may be a promising tool for modulating the fear extinction network, which plays
a pivotal role in PTSD treatment [66]. Furthermore, emerging evidence supports the
clinical efcacy of MST in MDD [68], bipolar depression [69], and schizophrenia
[70], hinting at potential benets for patients with PTSD.In studies examining MST
for MDD, patients have reported substantial improvements in depressive symptoms
and reductions in suicidal ideation, with fewer cognitive side effects compared to
ECT [20]. These results imply that MST may provide a comparable therapeutic
benet for PTSD, particularly in cases where other treatments have been ineffective.
Notably, no studies have specically investigated the efcacy of MST for
PTSD.However, ongoing clinical trials and future research are essential to explore
the potential application of MST in PTSD treatment further.
11.2.6.2 Safety
MST has demonstrated a promising safety and tolerability prole for treating various psychiatric conditions, including MDD and schizophrenia. However, its safety
in the treatment of PTSD has not been extensively studied. MST is generally considered more targeted than ECT, which results in a reduced side effect prole.
Common side effects of MST, such as headache, nausea, and transient memory loss,
are typically mild and resolve quickly after treatment [70].
When comparing the cognitive side effects of MST and ECT, MST has been
shown to cause less cognitive impairment [71]. This is particularly relevant for
patients with PTSD, who may already be facing cognitive challenges due to the
effects of their trauma. Despite its generally favorable side effect prole, MST carries potential risks, including the risk of seizure induction, as it involves anesthesia
and the induction of generalized seizures. Therefore, careful patient evaluation and
monitoring are crucial to ensure safety during MST.
11.2.6.3 Treatment Regimen
Since specic studies on MST for PTSD are lacking, the treatment regimen for this
application has not been denitively established. However, based on existing studies of MST for other psychiatric conditions, some general guidelines can be inferred.
MST typically targets the cortex, particularly the vertex or prefrontal cortex,
depending on the desired therapeutic effect and protocol [70]. For PTSD, the specic stimulation targets may need to focus on the neural circuits and brain regions
implicated in trauma-related responses, such as the prefrontal cortex and amygdala.
The intensity of MST stimulation is high enough to induce a seizure under anesthesia. While the exact intensity may vary depending on the patient’s tolerance and
the therapeutic goals, high-frequency MST (e.g., 100Hz) has been found to be
effective in alleviating symptoms of depression [68]. The optimal frequency for
308
PTSD treatment, however, remains unknown and will require further research to
determine.
MST treatment typically involves a series of sessions over several weeks, with
the number and duration of treatments adjusted based on patient response and
symptom severity. In general, longer MST treatment courses are associated with
higher remission rates in conditions like depression [66].
S. Sha et al.
11.2.6.4 Clinical Recommendations
While MST has not yet been specically studied for PTSD, its mechanisms of
action and the promising results observed in other psychiatric conditions suggest
that it could be a viable treatment option for PTSD.However, further research is
needed to explore the safety, efcacy, and optimal treatment regimens for MST in
PTSD, to determine its potential as a therapeutic tool for this disorder (See
Table11.1).
11.3 tDCS
11.3.1 Conventional tDCS
Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulatory
technique that has shown promise in modulating neuronal activity through the
application of a low-intensity direct current delivered via saline-soaked electrodes.
This method can inuence cognitive processes such as learning and memory
[72–75], making it a potential adjunct to treatments for various psychiatric disorders, including depression, schizophrenia, and PTSD [76, 77]. Conventional tDCS
is receiving growing attention as an adjunctive treatment for PTSD, owing to its
capacity to target specic brain regions associated with PTSD symptomatology [78].
11.3.1.1 Efficacy
In recent studies, conventional tDCS has demonstrated efcacy in reducing PTSD
symptoms. Small-sample, randomized double-blind trials have shown that tDCS
can alleviate hyperarousal, negative cognitive and emotional symptoms, as well as
symptoms of depression and anxiety in individuals with PTSD [76]. Research has
further highlighted that patients with PTSD often exhibit reduced volume and activation in regions such as the ventromedial prefrontal cortex (vmPFC) during fear
extinction processes [79]. As a result, studies have suggested that tDCS, when
applied during the consolidation phase of fear extinction, can enhance extinction
memory and potentially improve the treatment of PTSD [80].
Advancements in technology have led to the development of novel approaches
that combine tDCS with other therapeutic modalities, such as computerized cognitive training and virtual reality (VR). One study involved a computerized cognitive
program administered over 5weeks following tDCS treatment in a small group of
patients with PTSD.The results indicated signicant improvements not only in cognitive and emotional performance indicators but also in neurophysiological changes,
11 Post-traumatic Stress Disorder
309
as evidenced by electroencephalography (EEG) recordings taken before and after
treatment [81].
In the context of PTSD treatment, combining tDCS with VR has yielded even more
signicant improvements. A double-blind randomized trial found that the combination of tDCS and VR resulted in a signicant reduction in self-reported PTSD symptom severity. Similarly, a single-blind trial demonstrated that the combined treatment
group showed a decrease in physiological arousal and clinically signicant reductions
in PTSD symptoms compared to the VR-only group with sham stimulation [82, 83].
In conclusion, tDCS has demonstrated promising efcacy in treating PTSD
symptoms, along with associated emotional and cognitive sub-symptoms. However,
given the heterogeneous nature of PTSD and the variability in patient responses,
further research is necessary to optimize treatment parameters and determine longterm outcomes.
11.3.1.2 Safety
Conventional tDCS is widely regarded as a safe neuromodulatory intervention with
minimal serious adverse effects. In a study involving 12 male veterans with warzone-related PTSD, common side effects included mild headaches, skin irritation at
electrode sites, and transient tingling sensations, typically manageable with overthe-counter analgesics. Although rare, issues such as itching, burning, and erythema
have been reported in prior studies, yet larger-scale investigations in diverse populations have not corroborated these observations [82, 84].
Consequently, patients should be informed about potential side effects prior to
treatment, with careful monitoring both during and following the intervention.
11.3.1.3 Treatment Regimen
The optimal protocol for conventional tDCS in the treatment of PTSD remains
undetermined and warrants further investigation. However, several general parameters can be inferred from existing studies, including stimulation target, intensity,
frequency, duration, and treatment session count.
Research in PTSD, encompassing both animal models and human studies, has
revealed dysregulations in neural circuits, notably hyperactivity in the amygdala
and dorsal anterior cingulate cortex—regions involved in fear processing—alongside diminished activity in the vmPFC, a key area responsible for inhibiting fear
responses [85–87]. As such, the vmPFC is a primary target for tDCS in PTSD,
particularly for augmenting extinction learning [80].
Another frequently targeted area is the bilateral DLPFC, with its therapeutic efcacy demonstrated in a double-blind, randomized controlled trial. In this study, 40
patients with PTSD were randomly assigned to receive either 10 sessions of active
tDCS at 2mA to the right (cathode) and left (anode) DLPFC or sham stimulation.
The active treatment group showed signicant improvements across a spectrum of
PTSD symptoms as well as mood and cognitive sub-symptoms [76]. Additional
research has indicated that left prefrontal anodal stimulation enhances working
memory performance, with the effect being dependent on stimulation polarity and
site specicity [88].
310
S. Sha et al.
The standard tDCS protocol (<40min, 4mA, 7.2 Coulombs) has not been associated with serious adverse events or irreversible damage, even after over 33,200
sessions and 1000 repeated sessions across various subjects [89]. The majority of
studies employ 2mA as the stimulation intensity, with session durations typically
ranging from 20 to 30 min [76, 83]. An effective treatment regimen typically
involves administering ve to ten sessions over the course of 1 to 2weeks. The
frequency of stimulation varies across studies, with some conducting sessions daily
for 1–2weeks, while others employ intermittent schedules; however, research has
predominantly concentrated on continuous stimulation rather than intermittent protocols [60]. Evidence suggests that administering 6–10 sessions over 2–3weeks
yields relatively favorable outcomes [76, 83].
11.3.1.4 Clinical Recommendations
Based on existing evidence, typical clinical protocols for conventional tDCS in
the treatment of PTSD involve delivering 2mA tDCS to the DLPFC or vmPFC
for 20–30min per session. The number of sessions generally ranges from 10 to
20, administered over a period of 2–3weeks. Clinical trials have indicated that
targeting the DLPFC or vmPFC with 2mA tDCS can effectively reduce PTSD
symptoms, particularly those related to physiological arousal and re-experiencing [78, 82].
When combined with exposure therapy (such as VR exposure) or cognitive training, conventional tDCS has shown potential for enhancing treatment efcacy. The
integration of tDCS with VR, specically, has been noted as technically feasible and
may evolve into a valuable clinical adjunct [81, 83].
11.3.2 HD-tDCS
High-Denition Transcranial Direct Current Stimulation (HD-tDCS) represents an
advancement in noninvasive brain stimulation techniques, utilizing low-intensity
electric currents to modulate neuronal excitability. Unlike traditional pad-based
tDCS, which employs a single large anode and cathode, 4×1 ring HD-tDCS delivers more focal brain stimulation. This conguration surrounds a central electrode
with four “ring” electrodes, ensuring that the modulation of cortical excitability is
conned to the region enclosed by the ring electrodes. The peak electric eld intensity is localized to the central electrode, optimizing the precision of stimulation and
enhancing the current density within the target region, while minimizing effects on
nontarget areas. As such, HD-tDCS offers a promising approach for more targeted
and effective modulation of neuronal activity in the treatment of PTSD.
11.3.2.1 Efficacy
Research has explored the efcacy of HD-tDCS in PTSD, particularly for patients
exhibiting symptoms such as re-experiencing. Due to its ability to precisely and
deeply stimulate specic brain regions, HD-tDCS [84] may offer superior therapeutic effects compared to conventional tDCS.This is supported by previous studies
11 Post-traumatic Stress Disorder
311
demonstrating the effectiveness of HD-tDCS in treating other psychiatric conditions. For example, in aphasia treatment, HD-tDCS signicantly improved naming
accuracy and response time by precisely targeting higher cortical areas, outperforming traditional tDCS techniques [90].
However, patients with PTSD exhibiting specic symptom proles may require
longer or more intensive treatments, or more precise targeting, to achieve optimal
therapeutic outcomes. Given the small sample sizes and issues with reproducibility
in current studies, the ndings related to HD-tDCS in PTSD have not yet reached
the threshold for robust evidence-based recommendations. Nevertheless, the potential of HD-tDCS for treating PTSD, especially in patients with distinct symptomatology, remains an area of active interest. Future studies, with larger sample sizes
and rigorous methodologies, are needed to further validate and rene its therapeutic
applications.
11.3.2.2 Safety
HD-tDCS is widely recognized as a safe and well-tolerated intervention for
PTSD, with the most commonly reported mild adverse effects being itching and
tingling in studies involving patients with PTSD [84]. No signicant or severe
adverse events have been linked to HD-tDCS.However, studies involving other
populations, such as the elderly, frequently report sensations of tingling and
burning, with the majority of cases being mild, although 4% of individuals report
“severe” sensations [91]. These observations may have relevance for PTSD populations as well.
11.3.2.3 Treatment Regimen
Drawing from the theoretical frameworks and neuroanatomical models of PTSD, it
is postulated that targeting the LTC with HD-tDCS could lead to enhanced therapeutic outcomes. Given that the LTC and insula may engage in interactions with the
fear circuit, creating a feedback loop that exacerbates the maladaptive symptoms of
PTSD, and considering that the amygdala, hippocampus, and ventromedial prefrontal cortex constitute the “fear circuit” [92, 93], which is considered the physiological foundation of PTSD, focused and precise stimulation of the LTC may more
effectively address this deeply located brain region, which is difcult to target with
noninvasive techniques, thereby promoting symptom alleviation.
The literature indicates that administering HD-tDCS at 2mA for 20min across
consecutive working days (Monday to Friday), totaling ten sessions, can yield positive effects in patients with PTSD [84]. These results suggest that further investigation into the optimization of these treatment parameters is warranted.
11.3.2.4 Clinical Recommendations
Currently, while limited research exists on HD-tDCS for PTSD, the treatment has
demonstrated some efcacy. Additional clinical trials and replication studies are
essential to validate and expand these ndings and to identify the most effective
treatment parameters (see Table11.2).
312
Table 11.2 tDCS in PTSD
Clinical recommendations
Anode
tDCS
Conventional
tDCS
HD-tDCS Unclear Unclear Unclear Unclear Unclear NA
Abbreviations: HD-tDCS high-denition transcranial direct current stimulation
position
Unclear Unclear Unclear Unclear Unclear NA
Cathode
position
Intensity
(mA)
Length
(min)
Duration
(sessions)
S. Sha et al.
Levels+references
11.4 TMS vs. tDCS
11.4.1 Efficacy
A systematic review of 981 patients from 21 randomized controlled trials [94] compared the effectiveness of various physical therapies in alleviating PTSD symptoms
and comorbid conditions. Among the treatments evaluated, dual tDCS was found to
improve PTSD symptoms more effectively than HF-rTMS, which, in turn, was
more benecial than LF-rTMS.
TMS has been shown to improve core PTSD symptoms, including intrusive memories, avoidance behaviors, and hyperarousal [9–11]. The therapeutic effects of
rTMS on brain regions are frequency-dependent: low-frequency rTMS at 1 Hz
applied to the DLPFC reduces overactivity in the region, alleviating symptoms such
as hypervigilance [8, 95], while HF-rTMS targeting the DLPFC enhances emotion
regulation and mitigates excessive fear responses in patients with PTSD [96, 97].
Additionally, TMS has demonstrated potential to improve cognitive function, with
both left-sided and right-sided rTMS associated with cognitive enhancements, particularly with right-sided rTMS, which signicantly improves verbal uency [17].
tDCS has been shown to signicantly reduce PTSD symptoms, including hyperarousal, negative cognitive and mood changes, and anxiety [76]. Notably, dual
tDCS has been linked to a reduction in anxiety symptoms in patients with PTSD
during the follow-up phase, suggesting that the therapeutic effects on anxiety may
persist long-term [98].
While the effects of noninvasive stimulation are generally less durable for persistent disorders [99], Xu Guobin’s meta-analysis conrmed the long-term stability of
symptom relief in patients with PTSD treated with rTMS [10]. Previous studies
have indicated that the effects of follow-up treatment remain signicant for periods
ranging from 2weeks to 3months [12, 17, 18]. Conversely, Liu’s study found that
only the therapeutic effect of dual tDCS on anxiety symptoms remained signicant
during the follow-up period (from half a month to 6months, with a mean duration
of 2.2months) [94]. These observations suggest cautious optimism regarding the
long-term efcacy of neuromodulatory treatments for PTSD.
11 Post-traumatic Stress Disorder
313
11.4.2 Safety
Both TMS and tDCS are considered low-risk interventions, with side effects primarily involving physical discomfort, with transient mood disturbances observed in
TMS treatments [6]. No signicant difference was observed in the incidence of side
effects between the two groups [94].
11.5 ECT
11.5.1 Efficacy
To date, PTSD has not been considered an indication for ECT [100]. However,
mounting evidence suggests that ECT may be benecial for patients with refractory
PTSD [101], particularly those who have failed at least four different antidepressants and 12 sessions of cognitive behavioral therapy. ECT has also shown promise
in treating PTSD individuals with comorbid MDD [100, 102] and in providing
maintenance therapy for individuals with chronic PTSD (symptoms persisting for
more than 3months) [101].
Current evidence indicates that ECT can alleviate core PTSD symptoms, including intrusion, avoidance, and hyperarousal. However, it remains controversial
whether improvements in PTSD symptom severity are linked to concurrent improvements in depressive symptoms [100]. The comorbidity rate of PTSD and MDD is
high, with nearly half of patients with PTSD meeting the diagnostic criteria for
MDD [103], suggesting a signicant overlap between depression and PTSD.As a
result, distinguishing the specic effects of ECT on these two symptom clusters in
clinical studies presents challenges [104]. A recent meta-analysis suggested that
comorbid depression, given its high prevalence, may serve as an independent indication for ECT trials in patients with PTSD [105], though these observations require
further validation. Notably, no signicant differences in cardiovascular mortality or
all-cause mortality have been observed between PTSD and MDD individuals treated
with ECT and those without these comorbidities. However, ECT was independently
associated with reduced cardiovascular and all-cause mortality, as well as a lower
risk of suicide in patients with both depression and PTSD, showing more robust
outcomes compared to antidepressant treatment alone [102].
A previous study found that the intention-to-treat response rate for ECT in
patients with PTSD resistant to both pharmacological and psychotherapeutic interventions was 70%. Although the sample size was small, this suggests that ECT may
be particularly suitable for PTSD complicated by psychotic features [101].
In conclusion, while the acute-phase efcacy of MECT in improving core PTSD
symptoms appears promising, further supporting evidence is required to substantiate this claim. From a long-term clinical outcome perspective, ECT has been shown
to independently reduce the risk of suicide, cardiovascular diseases, and all-cause
mortality in PTSD individuals with comorbid MDD, with effects stronger than
those achieved by antidepressant therapy alone.
314
S. Sha et al.
11.5.2 Safety
The safety prole of ECT has been broadly validated in the general population, with
most side effects primarily affecting cognition [106]. Anterograde amnesia is typically transient, while retrograde amnesia can be long-lasting or, in some cases, permanent. However, due to the limited number of clinical studies involving ECT for
PTSD, specic safety data in this context remain sparse [107].
11.5.3 Treatment Regimen
There are relatively few clinical studies evaluating ECT in patients with PTSD.In
one prospective study [101], pretreatment medications included pentobarbital
(4–5 mg/kg) and succinylcholine (1 mg/kg), with ECT performed using the
MECTA-SR1 device. The protocol involved an 800mA current amplitude, 1.5ms
pulse width, and 50Hz pulse frequency. Stimulation duration was adjusted to ensure
full seizure induction, with EEG monitoring dened as lasting at least 25s. The
treatment regimen consisted of 6 sessions, with double temporal electrodes applied
twice a week.
In a recent meta-analysis [105], four studies utilized right unilateral ECT (RUL
ECT), while one study employed bilateral ECT (BL ECT). For patients who did not
respond adequately to initial RUL ECT, BL or bitemporal ECT (BT ECT) was
administered. The onset threshold for ECT varied from 100% to 600% over the
course of 6–14 treatments.
11.5.4 Clinical Recommendations
While PTSD has not been ofcially included in the indications for MECT, a notable
proportion of patients (approximately 10%) have received ECT for both major
depression and PTSD. This indicates that a signicant number of patients with
PTSD are already being treated with ECT.Future studies should include larger sample sizes, randomized controlled trials, and more rened patient populations to further evaluate the effectiveness and safety of MECT in treating PTSD [108].
11.6 Conclusion
This chapter provides an overview of TMS, tDCS, ECT, and their contemporary
variations in the management of PTSD.
Regarding rTMS, U-rTMS, particularly when high-frequency stimulation is
applied to the right DLPFC, has shown promising results in alleviating core PTSD
symptoms. B-rTMS, which targets both the right and left DLPFC with highfrequency stimulation, has also proven effective. However, the mixed outcomes
reported across existing studies have led to uncertainty regarding the optimal