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90
X. Yang et al.
4.3.2.2 Safety
Extensive evidence underscores the potential of HD-tDCS as an effective and safe
neurostimulation technique for bipolar disorder. Studies have reported favorable
outcomes across various brain targets in both short- and long-term follow-ups [70,
80]. For instance, in Zhang etal.’s study, no instances of epilepsy or seizures were
observed. However, 3 out of 28 participants in the active group and 2 out of 27in
the sham group reported burning and itching sensations. Additionally, two active
group participants experienced headaches, while one sham group participant
reported tingling sensations. Transient hypomania was noted in two active group
participants and one in the sham group. All adverse effects were deemed tolerable
and resolved by the conclusion of the treatment period. Despite these promising
ndings, current research on HD-tDCS in bipolar disorder remains constrained by
small sample sizes, single-center designs, and reliance on case studies. Future studies must address these limitations to validate the efcacy and safety of HD-tDCS in
broader populations. Furthermore, identifying optimal brain targets is crucial, as
therapeutic outcomes are likely to vary depending on the specic regions stimulated.
4.3.2.3 Treatment Regimen
Two studies [70, 81] investigating the application of tDCS for the treatment of
depressive episodes in bipolar disorder reported differences in their protocols.
Veenakumari etal. [81] implemented anodal stimulation of the right dorsolateral
prefrontal cortex (DLPFC) using a 4× 1 electrode conguration, with cathodes
positioned at adjacent electrode sites (AF4, AF8, FC2, FC6) and the central electrode at F4. In contrast, Zhang etal. [70] placed the anode over F3, with return
electrodes located at FP1, FZ, C3, and F7. The protocol involved 14 sessions, each
lasting 20min, with ramp-up and ramp-down periods of 30s each. These differences in protocol design could inuence therapeutic outcomes and patient adherence. Despite these discrepancies, both studies demonstrated the potential efcacy
of tDCS as a noninvasive neuromodulation technique for bipolar disorder.
4.3.2.4 Clinical Recommendations
The lack of robust evidence-based studies has left the clinical application of
HD-tDCS in bipolar disorder, including both depressive and manic episodes, an
unresolved issue (Table 4.3). The scarcity of empirical data has hindered the
Table 4.3 tDCS in bipolar disorder
Clinical recommendations
Anode
tDCS
Conventional
tDCS
HD-tDCS Unclear Unclear Unclear Unclear Unclear Both episodea
Abbreviations: HD-tDCS high-denition transcranial direct current stimulation, tDCS transcranial
direct current stimulation
a
Both episodes including depressive episode and mania episode
position
Unclear Unclear Unclear Unclear Unclear Both episodea
Cathode
position
Intensity
(mA)
Length
(min)
Duration
(sessions)
Episode: Levels
+ References
[8, 79]
[8, 79]
4 Bipolar Disorder
establishment of consensus on optimal clinical practices, leaving the eld of
HD-tDCS for bipolar disorder treatment open to ongoing debate [8, 79].
91
4.4 TMS vs. tDCS
4.4.1 Efficacy
TMS and tDCS are widely utilized noninvasive brain stimulation (NIBS) techniques
for treating bipolar disorder, particularly bipolar depression. A recent network metaanalysis encompassing 113 studies demonstrated that both TMS and tDCS exhibit
higher efcacy and acceptability compared to sham treatments for MDD and bipolar depression [40]. This analysis revealed superior response rates for several
modalities of TMS and tDCS over sham therapy, ranked by OR as follows: priming
TMS (OR=6.02), bilateral rTMS (OR=4.92), bilateral TBS (OR=4.44), lowfrequency right rTMS (OR=3.65), intermittent TBS (OR=3.20), high-frequency
left rTMS (OR=3.17), and tDCS (OR=2.65). All treatments demonstrated acceptability comparable to sham therapy.
While both TMS and tDCS are pivotal in the management of bipolar disorder,
they differ signicantly in their characteristics. TMS is frequently employed for
bipolar depression due to its rapid and robust efcacy, particularly in patients unresponsive to conventional antidepressants. In contrast, tDCS is an emerging modality
with promising potential for bipolar disorder treatment, though further research is
required to optimize its application and efcacy.
4.4.2 Safety
The safety proles of TMS and tDCS have been rigorously evaluated, with ndings
indicating that both techniques are generally safe and well-tolerated [40]. No signicant differences in dropout rates or severe adverse events were observed when
comparing active treatments to sham controls. However, left-sided excitatory stimulation, such as high-frequency rTMS over F3 (HF-rTMS-F3) and HD-tDCS targeting F3, may carry a heightened risk of side effects, including the potential induction
of hypomanic episodes, compared to right-sided inhibitory stimulation [40]. This
underscores the importance of careful patient monitoring and the customization of
stimulation parameters to ensure safety and efcacy.
Direct comparisons of safety proles between TMS and tDCS remain challenging due to methodological discrepancies, variations in patient demographics, and
differences in stimulation protocols across studies. To address these limitations,
RCTs with larger sample sizes and standardized evaluation criteria are necessary.
Such studies should systematically compare the safety and efcacy of TMS, tDCS,
and specic TBS protocols to establish more denitive recommendations for clinical practice.
92
X. Yang et al.
4.5 Conclusion
Both TMS and tDCS represent key components of a comprehensive treatment strategy for bipolar disorder, offering a viable alternative for patients who exhibit inadequate responses to traditional pharmacological interventions. It is crucial to
emphasize that the application of either modality necessitates oversight by qualied
medical professionals, in accordance with established clinical protocols, to safeguard patient well-being and maximize therapeutic outcomes.
As highlighted in this chapter, a variety of optimization strategies for TMS
exist; however, the most effective approach for treating bipolar disorder has yet to
be clearly dened. Moreover, while the combined use of TMS and tDCS has demonstrated efcacy in the treatment of MDD [82], its applicability to bipolar disorder remains inconclusive. Concurrently, China is working toward the establishment
of rapid antidepressant centers, which will integrate advanced treatments such as
MST and SAINT.However, the effectiveness of these therapies for bipolar disorder—particularly in cases of refractory bipolar depression or mania—remains
uncertain. Furthermore, certain biomarkers, including stimulation parameters [83]
and genetic markers [84], have shown potential in predicting the clinical effectiveness of TMS or tDCS in MDD.However, research on these indicators within the
context of bipolar disorder remains limited [8]. In summary, the growing body of
research and technological advancements indicate that TMS and tDCS will play an
increasingly signicant role in the management of bipolar disorder in the
near future.
Acknowledgments None.
Disclosure/Conicts of Interest The authors declare no conicts of interest in conducting this
study or preparing the manuscript.
Financial Support This study was funded by the Science and Technology Program of Guangzhou
(20251A011047, 20252A011018, 2023A03J0839, and 2023A03J0436), Science and Technology
Planning Project of Liwan District of Guangzhou (202201012), National Clinical Key specialty
construction project [(2023) 33], the Natural Science Foundation Program of Guangdong
(2023A1515011383, 2024A1515012578), the Science and Technology Program of Guangzhou
(202206010077), Guangzhou Municipal Key Discipline in Medicine (2021–2023), Guangzhou
Traditional Chinese Medicine and Integrated Traditional Chinese and Western Medicine Science
and Technology Project (20232A010014), Guangzhou High-level Clinical Key Specialty,
Department of Emergency Medicine of National clinical key specialty and Guangzhou Researchoriented Hospital. The funders had no role in study design, data collection and analysis, decision
to publish, or preparation of the manuscript.
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97
Schizophrenia
HuDeng, XinyueYang, ShutingLi, ShujuanPan,
andChundiWang
Abstract
Schizophrenia is a chronic and debilitating psychiatric disorder characterized by het-
erogeneous clinical manifestations and a complex etiology involving genetic predis-
position, environmental triggers, and neurodevelopmental abnormalities. This makes
it difcult to treat schizophrenia in a clinical setting. Although some patients with
schizophrenia may benet from clinical drug therapy, many individuals still suffer
from treatment resistance and poor disease prognosis. Transcranial magnetic stimu-
lation (TMS), utilizing pulsed magnetic elds to induce focal neuronal depolariza-
tion, and transcranial direct current stimulation (tDCS), employing weak direct
currents to modulate resting membrane potentials, constitute cutting-edge neuro-
modulation modalities with growing evidence for efcacy in refractory neuropsychi-
atric conditions. Over the past two decades, many clinical trials have been conducted
to nd a better and more effective therapy for schizophrenia. Unfortunately, the
results are mixed and no consensus exists. Hence, additional studies are needed to
determine the optimal stimulus parameters and to identify key variables that might
inuence individual responses to TMS or tDCS.An overview of TMS and tDCS for
schizophrenia is provided in this chapter.
5
Keywords
Noninvasive neurostimulation · Schizophrenia · TMS · tDCS
H. Deng · X. Yang · S. Li · S. Pan
Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School,
Beijing, China
C. Wang (*)
Department of Psychology, School of Humanities and Social Sciences, Beihang University,
Beijing, China
e-mail: wangchundi@buaa.edu.cn
© The Author(s), under exclusive license to Springer Nature Singapore Pte
Ltd. 2025
W. Zheng, Y. Ning (eds.), TMS and tDCS for Psychiatric Disorders,
https://doi.org/10.1007/978-981-96-8504-2_5
99
100
H. Deng et al.
Abbreviations
ADRs adverse drug reactions
AF3 Left Anterior Frontal 3
AH auditory hallucinations
AHRS the auditory hallucination rating scale
AMT active motor threshold
AtDCS Anodal transcranial direct current stimulation
AVH auditory verbal hallucinations
BDNF brain-derived neurotrophic factor
cTBS continuous theta burst stimulation
DLPFC dorsolateral prefrontal cortex
dTMS deep transcranial magnetic stimulation
ECT electroconvulsive therapy
EEG electroencephalogram
F7 Left Frontal 7
FC1 Left Frontal-Central 1
FC3 Left Frontal-Central 3
FC5 Left Frontal-Central 5
FT7 Left Frontal-Temporal 7
GDNF glial cell line-derived neurotrophic factor
HD-tDCS high-denition transcranial direct current stimulation
HF-rTMS high-frequency repetitive transcranial magnetic stimulation
Hz hertz
iCiTBS intensive cerebellar intermittent theta burst stimulation
iTBS intermittent theta burst stimulation
kg kilogram
LF-rTMS low-frequency repetitive transcranial magnetic stimulation
M1 area primary motor cortex
mA milliampere
MCCB the MATRICS consensus cognitive battery
MCF-B65 a gure-eight coil
MDD major depressive disorder
MEP motor-evoked potential
mg milligram
min minute
mm millimeter
MST magnetic seizure therapy
MT motor threshold
NIBS noninvasive brain stimulation
P1 Left Parietal 1
PANSS Positive and Negative Syndrome Scale
PO7 Left Parieto-Occipital 7
PSYRATS-AH Psychotic Symptom Rating Scale—auditory hallucinations
PTSD posttraumatic stress disorder