Repetitive Transcranial Magnetic Stimulation in Major Depression
Hiroe Alencar Braga1, Akila Macedo Freire1, Ageu de Oliveira Saraiva1, Alisson Cordeiro Moreira1,Flaviane Cristine Troglio da Silva2 and Modesto Leite Rolim Neto1,2*
1Faculty of Medicine, Estácio-FMJ, Juazeiro do Norte, Ceará, Brazil
2Post Graduation Program in Health Sciences –Faculty of Medicine of ABC, Santo André, São Paulo, Brazil
- *Corresponding Author:
- Modesto Rolim Neto
Faculty of Medicine, Estácio-FMJ
Juazeiro do Norte, Ceará, Brazil
Received date: Sep 27, 2016; Accepted date: Sep 29, 2016; Published date: Oct 03, 2016
Citation: Braga HA, Freire AM, Saraiva AO, et al. Repetitive Transcranial Magnetic Stimulation in Major Depression. J Neurol Neurosci. 2016, 7:5.doi: 10.21767/2171-6625.1000150
Major depression is the most common psychiatric disorder described, being a highly disabling disorder with a high prevalence in ocident and has a huge social and economic impact. With several effective treatments to combat depression, whether with drugs, with evidencebased psychotherapy or its association, most of these depressed patients or not outweigh the disease or reach partial improvement. This group is classified as depression resistant to treatment (TRD). Transcranial magnetic stimulation (TMS) is effective alternatives for nonresponsive cases. It is a brain intervention that modulates the activity of cortical areas and neural circuits associated with induction of non-invasive intracerebral current and its most common use is high frequency stimulation in the dorsal region of the left lateral prefrontal cortex (DLPFC). Several single-center, controlled studies TMS studies were made and in most cases, been proven antidepressant properties of TMS, despite certain recommendations for greater safety and efficacy in the treatment of depression.
Major depression; Transcranial magnetic
Major depression is the most common of all psychiatric
disorders [1,2]. It is a highly prevalent and disabling condition
associated with significant morbidity and mortality . While
depression can be effectively treated in majority of patients by
either medication or some form of evidence-based
psychotherapy [2,4], up to 20% of patients fail to respond to
standard interventions [2,5,6]. After acute-phase
pharmacotherapy, psychotherapy, or both, most depressed
patients either do not improve or achieve only partial
symptomatic improvement [7-12]. This group is considered to
have treatment-resistant depression (TRD) .
The lack of sufficient treatment response and the enormous
impact of the disorder make the development of alternative
treatment approaches a priority .
Electroconvulsive therapy (ECT) is considered an effective
alternative for such patients, but necessitates administering
general anesthetic, induces a seizure, and causes significant
memory [3,14] and learning [3,15] impairments. Transcranial
magnetic stimulation (TMS) has been proposed as a refined
TMS is a noninvasive technique used to apply magnetic
pulses to the brain. The pulses are administered by passing
high currents through an electromagnetic coil placed upon the
scalp that can induce electrical currents in the underlying
cortical tissue, thereby producing a localized axonal
Repetitive TMS (rTMS) refers to TMS applied repeatedly
during a session [12,17-19]. It was introduced as a promising
new treatment option for depression and showed beneficial
effects in single-centre studies [20-23].
Numerous lines of evidence deriving from different research
and clinical methodologies attest that depression involves
integrated neural pathways linking select cortical, subcortical,
and limbic sites and their related molecular mediators [24-29].
The H-coil is a novel rTMS tool, which enables direct
stimulation of deeper and larger brain volumes [13,16,30-32].
The intensity of stimulation was found to be a critical factor in
the therapeutic effect of DTMS. Studies questioning the
efficacy of standard TMS in the treatment of depression
concluded that among other factors, higher intensities are
needed to reach clinical significance [3,33,34]. In the current
study, direct stimulation of deeper brain regions by the H-coils
resulted in very high response and remission rates .
Studies showed that deep TMS utilizing the H-coil is
generally safe and effective as an augmentation treatment in
patients who did not sufficiently respond to at least two
antidepressant medications in the current episode . The
efficacy of dTMS and standard TMS cannot be compared at the
moment because previous studies investigating rTMS not only vary by TMS parameters, but also differ by inclusion criteria,
patient characteristics and efficacy criteria .
Adverse events reported were principally limited to scalp
discomfort or pain within the confines of the TMS session itself
and were mostly transient phenomena in the first weeks of the
TMS course. The most serious side effect that has been
reported with TMS is a seizure [35,36]. There have been no
reported seizures in therapeutic trials in depression with the
application of safety guidelines developed following initial
reports of seizures with high frequency stimulation [37-40].
Methods to account for individual differences in anatomy
have been proposed including targeting based on standardized
EEG electrode positions [41,42], or specific MRI coordinates
[42,43-45]. Most clinical rTMS protocols have stimulated the
left DLPFC. Recent studies have shown that different DLPFC
sub regions stimulated by standard protocols vary considerably
in terms of their connectivity with medial prefrontal structures
such as the subgenual cingulate gyrus [13,46,47], which
appears to be an important region involved in the
pathophysiology of MDD [2,13].
It remains difficult to draw general conclusions about the
antidepressant efficacy of rTMS because of heterogeneous
study designs, variable stimulation parameters and low sample
sizes [23,48]. Despite the encouraging results presented in this
study, there are others limitations that should be addressed
1. The rTMS has antidepressant properties that are
supported by a number of lines of research , however,
Herwing et al., observed the same rates of responders
(31%) in both groups (real and the sham treatment
groups), implying that even if many more patients had
been treated the outcome in the primary efficacy variable
would not have been any different [23,49].
2. The rTMS is applied in adults between the ages of 18 and
70. There is a suggestion of reduced efficacy in the elderly
from the limited trials in this population to date and more
research is required before rTMS is more widely applied
in this age group .
3. Greater rates of overall response and remission would
likely be seen if TMS were delivered in combination with
pharmacotherapy, as was recently demonstrated with
electroconvulsive therapy [12,50].
Although most studies indicates clinical significance of the
proposed procedure, there is still no consensus on the ideal
protocol to be adopted to optimize the results of the therapy,
as well the impact of their long-term effects, making it hasty to
actual clinical use. Thus, we conclude that there is a clear need
for more research, but with better planning, aiming to bring a
new treatment and actual effectiveness of major depression
for the population.
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