https://doi.org/10.53453/ms.2026.5.11
Therapeutic applications and outcomes of transcranial magnetic
stimulation: literature review
Meda Maliorė¹, Kamilė Kulytė¹, Jonas Montvidas²
¹Faculty of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania
²Department of Psychiatry, Faculty of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania
Abstract
Background. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method in which a
magnetic field generated by alternating electric current induces electrical currents in the cerebral cortex. Therapeutic
stimulation most commonly targets the dorsolateral prefrontal cortex (DLPFC), where reduced metabolic activity is
associated with depressive symptom severity.
Aim. To analyze the therapeutic indications and clinical outcomes of TMS based on currently available literature.
Materials and methods. A literature search was performed in the PubMed database between 2025-05-01 and 2025-
07-01 using predefined English keywords. A total of 78 articles were identified, of which 32 met the inclusion criteria.
Publications from 2014 to 2025, including systematic reviews, randomized clinical trials, reviews, and retrospective
studies in adult populations, were included.
Results. Available evidence shows that repetitive transcranial magnetic stimulation (rTMS) is a safe and effective
treatment for treatment-resistant depression. Stimulation of the left DLPFC significantly reduces depressive
symptoms, with clinical response commonly defined as a ≥50% symptom reduction. Approximately 60% of patients
with suicidal ideation demonstrated improvement after treatment. In bipolar disorder, rTMS increased the probability
of clinical response compared with placebo. In schizophrenia, low-frequency rTMS and continuous theta-burst
stimulation (cTBS) reduced auditory hallucinations and improved negative symptoms.
Conclusions. TMS is an effective adjunctive treatment for treatment-resistant depression and shows promising
benefits in bipolar disorder and schizophrenia, although further standardized studies are needed.
Keywords: transcranial magnetic stimulation, repetitive transcranial magnetic stimulation, theta burst stimulation,
continuous theta burst stimulation, intermittent theta burst stimulation, dorsolateral prefrontal cortex,
electroencephalogram, Hamilton Depression Rating Scale.
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Medical Sciences 2026 Vol. 14 (3), p. 88-96, https://doi.org/10.53453/ms.2026.5.11
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1. Introduction
TMS began to be applied for therapeutic purposes in
1985, when the first modern TMS device was invented
[1]. It is a non-invasive method of brain stimulation in
which specific cortical regions are stimulated by
electrical impulses, thereby modulating neuronal acti-
vity. The mechanism of action of TMS is based on a
magnetic field generated by alternating electric
current, which induces the flow of electrical impulses.
During electrical stimulation, current flows between
two electrodes, while short, high-current pulses are
generated in a magnetic coil, thereby creating a
magnetic field. The magnetic impulse is of very high
energy and typically lasts approximately 100 μs. The
magnetic coil plays an important role in generating
and maintaining the effectiveness of the propagating
impulse [2]. By selecting the appropriate position of
the magnetic coil, impulses are directed toward the left
dorsolateral prefrontal cortex (DLPFC). This region is
associated with the pathogenesis of mood disorders
[3]. Activated brain cells release neurotransmitters
such as serotonin, norepinephrine, and dopamine.
Thus, it is believed that during the TMS process,
neurotransmitter imbalance is restored, the cerebral
cortex is activated after the first stimulation procedure,
and positive results become evident after several
weeks [4].
The duration of the therapeutic procedure and the
frequency of impulses are selected individually, taking
into account the indication for TMS and the specific
application algorithm. Several types of TMS are used
in treatment, differing in impulse characteristics and
frequency. Repetitive transcranial magnetic stimu-
lation (rTMS) is a form of TMS in which the cerebral
cortex is stimulated with repeated magnetic pulses to
modulate neuronal activity. Low-frequency rTMS (1
Hz or less) is used to achieve cortical inhibition,
whereas high frequencies (5–20 Hz) exert an
excitatory effect by increasing neuronal activity in the
cortex [5]. In some cases, a shorter rTMS method
known as theta-burst stimulation (TBS) is applied.
During this procedure, impulses consist of three 50 Hz
triplets repeated at a frequency of 5 Hz [6]. TBS may
be continuous continuous theta-burst stimulation
(cTBS) or intermittent theta-burst stimulation (iTBS).
TBS is based on two main principles: repeated
stimulation over a short period produces an effect no
inferior to rTMS in controlling depressive symptoms,
and intensively scheduled sessions have long-term
efficacy [7]. The duration of a TMS treatment course
may last several weeks, with sessions most commonly
conducted 5 days per week, each lasting
approximately 20–40 minutes [8].
During the TMS procedure, the patient’s and the
magnetic coil’s positions are selected, and stimulation
parameters are determined. During the procedure, the
patient sits in a reclining chair with back and head
support, aiming to achieve the most comfortable body
position possible. Hearing protection is often used to
protect against sounds generated by stimulation. To
avoid unnecessary head movements that may reduce
treatment accuracy, the patient’s head is stabilized
during stimulation. The device generating magnetic
impulses is placed close to the patient’s head, and the
coil is positioned directly over the individually
determined stimulation area on the scalp. Prior to
stimulation, the individual intensity of magnetic
impulses is determined by establishing the patient’s
individual “motor threshold” – the lowest level of
magnetic stimulation that induces a slight contraction
of the small muscles of the hand or fingers. During the
course of treatment, the dose is usually increased from
80% to 120% of the patient’s individual motor
threshold. During stimulation, the patient may
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experience mild tingling or vibration in the head area,
as well as movements of the fingers, jaw, or eyebrows.
After the procedure, the patient may return to daily
activities, and no special precautionary measures are
required [9]. The main advantages of TMS are that the
procedure is non-invasive, does not require anesthesia,
has no systemic side effects, and is safe and effective.
In addition, TMS does not reduce alertness and does
not require hospitalization.
2. Materials and methods
The search for articles was conducted in the PubMed
database during the period from 2025-05-01 to 2025-
07-01. The following English keywords were used for
the search: transcranial magnetic stimulation,
repetitive transcranial magnetic stimulation, theta-
burst stimulation, intermittent theta-burst stimulation,
continuous theta-burst stimulation, dorsolateral
prefrontal cortex, treatment-resistant depression, beam
F3 method, 5.5 cm rule, application of TMS in the
treatment of schizophrenia, application of TMS in the
treatment of bipolar disorder.
Using the keywords and their combinations, 78
articles were identified. A total of 32 scientific articles
meeting the inclusion criteria were included in the
review. Sources not older than 11 years, published
between 2014 and 2025, were included in the review.
Systematic reviews with or without meta-analysis,
randomized clinical trials, reviews, and retrospective
studies corresponding to the topic and examining the
application of TMS in the adult population were
selected for analysis. Sources older than 11 years,
written in languages other than English, duplicated, or
unavailable in full-text format were excluded from the
review.
3. Results
3.1 TMS in the treatment of depression
First-line evidence-based methods for the treatment of
depression are psychopharmacotherapy and
psychotherapy; however, in cases of treatment-
resistant depression, these methods alone are often
insufficient. Approximately 30% of patients may be
diagnosed with treatment-resistant depression – when
no clinical improvement is observed despite the use of
at least two antidepressants at adequate doses for a
sufficient duration [9]. In cases of treatment-resistant
depression, second-line treatment methods such as
TMS become particularly important.
The use of rTMS in the left DLPFC region is an
evidence-based method for the treatment of resistant
depression. It is known that patients with depression
exhibit lower metabolic activity of gray matter in the
left DLPFC region [10]. From this, it is inferred that
an imbalance between the left and right prefrontal
cortex may be associated with the pathophysiology of
depression. Most commonly, 10 Hz stimulation is
applied in such patients [11]. To achieve clinical
remission and a favorable long-term clinical response,
at least 6–8 sessions are required. Moreover,
neurophysiological evidence suggests that a greater
effect of rTMS on cortical excitability is achieved if
the second rTMS session is performed within 24 hours
of the first session [12].
Precise selection of the cortical target for stimulation
in the DLPFC region has not yet been standardized.
Two methods for determining the exact stimulation
site have become primary options – the 5.5 cm rule and
the Beam F3 method. The 5.5 cm method is older and
determines the stimulation site 5.5 cm anterior to the
motor cortex (M1) region from the point that elicits
movement of both of the patient’s hand fingers. The
Beam F3 method is anatomically based, with electrode
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positioning determined using the international 10–10
electroencephalography (EEG) coordinate system. To
maximize accurate localization of the stimulation
target, neuronavigation based on individual
neuroimaging data is increasingly applied, allowing
more precise positioning of the magnetic coil and
increasing treatment effectiveness compared to
standard anatomical landmarks [13]. According to
analyses, neuronavigation is the most accurate
method; the Beam F3 method demonstrates greater
accuracy compared to the 5.5 cm rule; however, no
significant clinical difference in depression symptom
relief has been observed between these methods
[14,15].
In investigating the effect of rTMS in reducing the
severity of depressive symptoms, a retrospective study
assessed symptom reduction and remission depending
on coil position during the procedure. The authors
reported that dysphoric symptoms (depressed mood,
reduced interest, suicidality) improved more when the
stimulation target was directed toward the left DLPFC,
whereas somatic symptoms (insomnia, decreased
libido, irritability) were most effectively influenced by
stimulation of the left dorsomedial prefrontal cortex
(DMPFC) [16]. According to recent studies, overall
improvement in depressive symptoms indicates that,
despite highly precise focal cortical stimulation, rTMS
stimulates broad neuronal networks in the brain and
exerts a positive effect on most depressive symptoms
[17].
Standard rTMS may also be beneficial for patients
with depression who are at risk of suicide. A
retrospective cohort study published in 2025 analyzed
the application of bilateral rTMS in the DLPFC region
in individuals with depression experiencing suicidal
ideation and anxiety symptoms. During the study,
patients received 30 rTMS sessions, and suicidal
ideation was assessed using the third item of the
Hamilton Depression Rating Scale (HDRS). After
treatment, suicidal symptomatology was reduced in
approximately 60% of patients, and significant
reductions in depressive and anxiety symptoms were
observed [18].
A newer TBS methodology is increasingly applied in
the treatment of depression. The literature frequently
compares two main neuromodulation methods for
treating antidepressant-resistant depression: high-
frequency rTMS (10 Hz) and intermittent theta-burst
stimulation (iTBS, 50 Hz). According to analyses, the
effectiveness of both methods in reducing depressive
symptoms and achieving remission is similar.
However, iTBS has a greater practical advantage – a
significantly shorter stimulation duration of only 192
seconds [19–21].
3.2 TMS in the treatment of bipolar disorder
Bipolar disorder is characterized by alternating
episodes of mania and depression. Depressive
symptoms occur in 70–80% of symptomatic bipolar
disorder episodes and result in significant impairment
in daily functioning. As in the treatment of depression,
psychopharmacotherapy and psychotherapy are first-
line treatment methods; however, in not all clinical
cases are these methods effective in achieving
regression of psychopathological symptoms [22].
TMS in the treatment of bipolar disorder may be an
effective method, particularly during depressive
episodes. In the literature, the response rate to rTMS
in bipolar disorder treatment reaches approximately
40–50% [23].
During a depressive episode, functional, structural,
and metabolic disturbances are observed in certain
brain regions: hyperactivity of limbic regions
(amygdala, hippocampus) and decreased functional
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activity in prefrontal areas (DLPFC, anterior cingulate
cortex) [24]. These regions are associated with
emotion regulation, motivation, and self-control.
According to neuroimaging data, TMS application is
associated with increased activity in the anterior
cingulate and prefrontal cortices responsible for mood
regulation [25].
A systematic meta-analysis published in 2021
evaluated the efficacy of rTMS in treating depressive
episodes of bipolar disorder. Clinical response was
defined as a ≥50% reduction in depressive symptoms
from baseline according to a depression rating scale.
Analysis of 14 randomized controlled trials revealed
that rTMS increased the likelihood of clinical response
by 2.5 times compared with the placebo group. The
study emphasized that the most significant clinical
effect is achieved by stimulating the left DLPFC using
high-frequency rTMS [26].
On the other hand, scientific literature indicates that
the effect of TMS in the treatment of bipolar disorder
remains limited due to the small number of studies,
small sample sizes, and heterogeneity of control
groups. More comprehensive and detailed studies are
required to demonstrate the efficacy of rTMS in the
treatment of this disorder [27].
3.3 TMS in the treatment of schizophrenia
In approximately one-third of patients with
schizophrenia, symptom control with conventional
antipsychotic medications is ineffective [28].
Treatment-resistant schizophrenia is defined as the
failure to achieve symptom remission after the use of
two antipsychotic medications for a sufficient duration
(approximately 6–8 weeks) at optimal doses. In the
literature, the benefit of TMS in the treatment of
treatment-resistant schizophrenia is associated with
improved control of persistent auditory hallucinations
and improvement of negative symptoms [29,30].
Auditory hallucinations are associated with increased
activity in the left temporoparietal region, the activity
of which is targeted for reduction during TMS
treatment. According to studies, low-frequency rTMS
(1 Hz) is most commonly used in treatment. It has been
established that this frequency may help reduce neural
activity and the intensity of hallucinations [31].
Continuous theta-burst stimulation (cTBS) may also
be used, during which TBS is delivered continuously
for approximately 20–40 seconds. When comparing
the therapeutic effects of rTMS and cTBS in the
treatment of auditory hallucinations, the literature
emphasizes the superiority of the cTBS method [32].
In the literature, rTMS is considered a promising
adjunctive treatment method for patients experiencing
medication-resistant auditory (verbal) hallucinations.
According to recent randomized clinical trials, this
method may significantly reduce the intensity and
frequency of hallucinations compared with placebo
stimulation, and the effect may persist during the
follow-up period [33].
Negative symptoms – such as low motivation and
emotional withdrawal – are often insufficiently
corrected with conventional antipsychotic
medications. To address negative symptoms, the left
DLPFC is most commonly stimulated, as its
insufficient activity is associated with the
pathophysiology of negative symptoms. High-
frequency TMS stimulation (10 Hz or higher) is used
to increase brain activity and alleviate negative
symptoms. According to research data, patients
undergoing TMS report greater motivation and
improved cognitive and social functioning [33].
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4. Discussion
This literature review underscores the growing role of
transcranial magnetic stimulation as a clinically
relevant neuromodulation approach in major
psychiatric disorders, particularly in patients who do
not respond adequately to standard treatments. In
treatment-resistant depression, stimulation of the left
dorsolateral prefrontal cortex is the most consistently
supported target, in line with neurobiological models
emphasizing functional imbalance within prefrontal–
limbic networks. Comparable efficacy between high-
frequency rTMS and intermittent theta-burst
stimulation suggests that shorter stimulation protocols
may improve feasibility without compromising
therapeutic outcomes. Emerging evidence also
indicates a potential beneficial effect on suicidality,
which is especially relevant for high-risk patient
populations.
In bipolar disorder and schizophrenia, therapeutic
effects of TMS appear to depend on symptom-specific
targeting of dysfunctional neural circuits. Depressive
episodes in bipolar disorder may benefit from
excitatory prefrontal stimulation, although current
evidence is limited by small sample sizes and
methodological heterogeneity. In schizophrenia,
inhibitory stimulation of temporoparietal regions is
associated with reductions in auditory hallucinations,
while excitatory prefrontal stimulation may alleviate
negative symptoms. Despite promising findings,
variability in study design, stimulation parameters,
and outcome measures restricts the generalizability of
results. Overall, TMS emerges as a safe and promising
adjunctive treatment for treatment-resistant
depression, with potential applications in bipolar
disorder and schizophrenia that warrant further large-
scale, standardized clinical trials.
5. Conclusions
Transcranial magnetic stimulation is a safe and
clinically effective adjunctive treatment, particularly
for treatment-resistant depression. The strongest
evidence supports stimulation of the left dorsolateral
prefrontal cortex using repetitive transcranial
magnetic stimulation or intermittent theta-burst
stimulation, both of which significantly reduce
depressive symptoms.
In bipolar disorder, TMS demonstrates beneficial
effects mainly during depressive episodes, although
current evidence remains limited by small and
heterogeneous study samples. In schizophrenia,
symptom-specific stimulation protocols may reduce
auditory hallucinations and improve negative
symptoms.
Overall, TMS represents a promising
neuromodulation strategy in psychiatry; however,
larger, methodologically standardized studies are
required to optimize stimulation targets, treatment
parameters, and long-term outcome assessment.
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