Transcranial magnetic stimulation: A review of its evolution and current applications.

Repetitive transcranial magnetic stimulation (rTMS) is a recently developed noninvasive brain stimulation method for the treatment of psychiatric and neurological disorders. Although, its exact mechanism of action is still not clear, current evidence points toward its role in causing long-term inhibition and excitation of neurons in certain brain areas. As evidence steadily grows in favor of rTMS as a therapeutic tool; there is a need to develop standardized protocols for its administration. There have been no reports of any serious side effects with rTMS, though its use is restricted in those having magnetic implants or recent adverse neurological or cardiac event. Of all the psychiatric indications of rTMS, the evidence is most robust for treatment of refractory unipolar depression. This paper reviews contemporary literature highlighting the evolution of rTMS as a diagnostic and therapeutic tool, especially in the management of treatment-resistant depression.

Energy is dynamic, has a frequency, can change its form and is electromSagnetic (EM) in nature. All atoms, chemicals and cells produce EM fields (EMFs) of their own and all 70 trillion cells in the body communicate via EM exchanges.[1] Disruption of EM flow of energy in cells can causes impaired cell metabolism and its role and that may be the underlying cause of any disease process. These principles have led to an explosion of information pertaining to understanding of normal and abnormal brain in the past few decades. Barker et al. discovered the induction of finger and foot movements through the use of magnetic coil placed on the motor cortex.[2] Transcranial magnetic stimulation (TMS) is a neurophysiological procedure for noninvasive stimulation of the nervous system. It involves the application of rapidly changing magnetic field to the superficial layers of the cerebral cortex, which locally induces small electric currents, known as “Eddy or Foucault currents.” Cerebral cortex acts as a secondary coil in this situation.[3] TMS has an advantage over electroconvulsive therapy (ECT) as it is focused and bypasses the impedance of skull and superficial tissues. Therefore, it needs lesser stimulus strength and need for a true seizure or any form of anesthesia is completely obviated. However, despite the plethora of evidence supporting its usefulness in selected cases, skeptics continue to question its efficacy and the usage of repetitive TMS (rTMS) is still less. Therefore, a need was felt to systematically review the data on evolution and use of TMS in the treatment of refractory depression. We searched the PubMed/MEDLINE, EMBASE, PsycInfo, and Web of Science from inception up until July 2018. Two authors (AC and RKS) independently performed the search. Disagreements were discussed with other authors (PSB and KS) and resolved by consensus.

THE DEVELOPMENT OF MODERN TRANSCRANIAL MAGNETIC STIMULATION

Experiments on electrical stimulation of cerebral cortex started somewhere in 1874 in which contralateral motor response was elicited. The laws of electro-magnetic induction were given by Faraday in 1881.[4] d’Arsonval (1896) pioneered the use of magnetic fields to induce cortical stimulation.[5] In 1959, Kolin et al.[6] achieved nerve stimulation by using magnetic energy in frogs which laid the foundation for EM stimulation of neural tissue for diagnostic and therapeutic purposes. In the past few years, there have been rapid advances in the development of shape of coils to ensure concentrated magnetic field to achieve better control over the spatial extent of excitation. While the old form of treatment took up to 37 min per session, with high-frequency (HF) theta-burst stimulation the session may last for few minutes only.[7] It is likely that treatment protocols will undergo further refinements in the years to come making it more comfortable for patients.

Mechanism of action

TMS uses principles of EM induction. According to the principle of EM induction when an electric current is passed through a coil (primary coil), a magnetic field is generated. When the magnetic flux flows to the secondary coil (neural tissue), a secondary electrical field is induced, and this causes stimulation of the same.[5] Neurons have bent or curved axonal processes, passing at right angles to the lines of force of the magnetic field. They act like secondary coils and thus experience electrical effects.[89] Therefore, by changing the direction of current flow at HFs, rapidly alternating magnetic fields can be generated which in turn stimulate the underlying neurons and their fibers. The phenomenon of applying such stimulation in pulses is known as pulsed EMF stimulation which causes persistent depolarization. These pulsed stimulations are known to correct impaired functioning of cells and aid healing. Repetitive TMS works on similar principles and thus leads to observable clinical effects.[10]

EFFECTS OF TRANSCRANIAL MAGNETIC STIMULATION

The effect of rTMS stimulation on the cortical surface depends on the frequency of pulses of stimulation. At low frequency (LF), i.e., <1 Hz, rTMS is inhibitory to the underlying cortex while stimulation at HF, i.e., >5 Hz, it is excitatory.[1112] In TMS studies, cortical excitability (CSE) can be assessed by either calculation of resting motor threshold (RMT) or by calculation of Motor evoked potential (MEP). RMT is the minimal stimulation intensity required to produce a reliable motor response (twitch) in a peripheral muscle. The strength of the stimulus is then calculated based on RMT and normally, it is 120% of the RMT. In the other method to calculate CSE, the test stimulus is adjusted to produce MEP responses up to 0.5 mV. MEP size is the averaged response to a series of pulses applied at consistent stimulator intensity. HF rTMS (i.e., >5 Hz) appears to produce a persistent increase in MEP size and a reduction in cortical inhibition.[13]

The effects of TMS can be acute or prolonged depending on the mode of stimulation.

Acute effects

Acute effects of TMS will depend on the area of the cortex being stimulated. In the primary motor cortex, it produces a muscle activity referred to as motor evoked potential (MEP). In the occipital cortex, it generates flashes of light or visual distortions also known as phosphenes. In other areas, it may lead to slowed cognition or speech arrest.[14]

Prolonged effects

rTMS can increase or decrease the excitability of the cortical neurons depending on the frequency of stimulation. The mechanism of these effects is believed to reflect changes in synaptic efficacy akin to long-term potentiation or long-term depression. Other proposed mechanisms include alteration in levels of neurotrophic factors such as BDNF, modulation of CSE, and functional connectivity among brain circuits.[8] In a systematic review of patients treated with ECT, Fidalgo et al. reported a correlation of clinical outcome with changes in BDNF levels.[15] Although the study was conducted on patients undergoing ECT, the underlying biological mechanisms are akin to rTMS.

Depth of stimulation

Depending on the type of coil and intensity of stimulus used, depth of stimulation can vary from 2 to 4 cm below the cortical surface. This means that only superficial brain structures can be stimulated.[13] Therefore, achieving equilibrium in depth-focality trade-off is a matter of intense research. Figure-8 type coils exhibit superior depth-focality than other coils.[1617]

Administration of transcranial magnetic stimulation

Informed consent – All patients are to be informed about the procedure, role in treatment, and expected adverse effects.

Transcranial magnetic stimulation safety screen – It is a standard set of 13 questions proposed by Rossi et al.[18] on behalf of the International Federation of Clinical Neurophysiology.

Food and Drug Administration (FDA) recommends at least 20 sessions spread over 4–6 weeks at a frequency of at least 5 times a week for treatment-resistant depression (TRD). It is also important to measure the symptoms with the help of a standardized questionnaire to monitor weekly progress or lack of it. A self-rated questionnaire in local vernacular (like Beck's Depression Inventory) is a useful instrument as it eliminates observer bias.[1920]

Scalp position of coil

While administering TMS, it is important to determine the position of the scalp and coil orientation for optimal therapeutic effects. In experimental models, the growing cells respond differently to moving electric fields. They tend to align preferentially either parallel or antiparallel to the field vector, a process known as galvanotaxis.[21] Forces in the direction perpendicular and parallel to the electric field are in competition with one another in a voltage-dependent manner, which ultimately govern the trajectories of the cells in the presence of an electric field.[22] Since hypofunctioning of the left dorsolateral prefrontal cortex (DLPFC) has been implicated in the pathophysiology of several psychiatric illnesses including depressive disorder; it remains the preferred area for stimulation in most of the studies.[23] There are two ways of determining surface landmark of DLPFC:

5 cm technique – About 05 cm toward the left of the vertex a point is marked and about 02 cm ahead of that lies the motor cortex. The motor cortex is functionally localized as a scalp position where TMS evokes a motor movement and a measurable motor-evoked potential (MEP) in the contralateral hand. The prefrontal cortex stimulation site is determined as 5 cm anterior further ahead of the motor strip in the parasagittal line. It corresponds to an area between F3 and F5 position of 10–20 system of EEG recording.[24]

Neuro-navigational method – This method is theoretically more precise and employs MRI scan to pinpoint DLFPC with live video navigation. Fitzgerald et al.[25] studied 51 patients with treatment-resistant depression using this method and compared matched controlled subjects with standard 5 cm technique and found the superior response at the end of 3 weeks. However, the method is yet to gain popularity probably owing to the high costs of equipment involved.[26]

According to existing literature, 5 cm method remains fairly reliable and popular method as far as daily rTMS sessions are concerned.

Coil orientation in repetitive transcranial magnetic stimulation

In routine clinical and experimental models with rTMS, the amplitude of muscle evoked potential (MEP) is an indicator of the maximum effect of a particular orientation with reference to head position. Optimal stimulation has been reported if coil current was at an angle of 45° with respect to the sagittal plain.[2728]

Terminologies and dosing considerations associated with transcranial magnetic stimulation

These are the terms frequently encountered while using rTMS in either experimental or treatment models. A detailed description of these terms is given in Table 1. It is to be noted that modern rTMS machines have inbuilt software which automatically do most of these calculations though RMT has to be determined by one of the above-mentioned methods and pre-selected protocol has to be mentioned to the machine.[89]

Table 1

Various terms used in transcranial magnetic stimulation[58]

Term	Description
Stimulus strength	A measure of magnetic field, generally expressed in terms of percentage of maximum machine capacity (about 1-3 T)
MT	Minimum stimulus strength that produces 5 motor responses out of 10 stimuli when applied over a specified muscle area e.g., thumb area
Frequency	Number of stimuli given in 1 s
Single pulse	Single stimulus given after fixed interval, for example, after every 5 s
Frequency	The number of stimuli in a given pulse
Pulse train	Several pulses administered continuously in a given period of time
Inter-train interval	The time gap between two trains
Repetitive TMS	Trains of pulses applied to one brain area, slow: Low frequency <1 Hz, fast (high frequency) >1 Hz
Theta burst	Three magnetic pulses with an inter-stimulus interval of 20 m (50 Hz) were applied repeatedly every 200 m representing the theta rhythm of 5 Hz. (Hence named theta as it corresponds to theta rhythm of EEG)
Session	A time period in a day when rTMS is administered; typically in one session several trains are administered (1200-3000)

MT - Motor threshold; TMS - Transcranial magnetic stimulation; EEG - Electroencephalography; rTMS - Repetitive TMS

Treatment protocols and their efficacy

A brief summary of these protocols and the results are given in a tabular form as per Table 2. In the past two decades, research has focused on establishing sound protocols which could be replicated across various studies. However, the field is still wide open and newer protocols are being proposed.

Table 2

Various protocols used for treatment resistant depression

Years	Authors	Protocol/procedure/finding/remarks
2002	Boutros et al.[29]	Open label singe-blind study. Twenty one patients treated with sub-threshold (80% RMT) for 10 sessions over 2 weeks (20 Hz, 2-s trains, 20 trains). No meaningful clinical gain achieved
2005	Couturier[30]	Systematic meta-analysis and review of various protocols. rTMS is no different from sham treatment in major depression
2010	George et al.[31]	Sham controlled randomized trial. 199 TRD patients. Left prefrontal cortex at 120% MT (10 Hz, 4-s train duration, and 26-s intertrain interval) for 37.5 min (3000 pulses per session) using a figure-eight solid-core coil. The odds of attaining remission were 4.2 times greater with active rTMS than with sham
2011	Hadley et al.[32]	Open-label study. Nineteen patients received daily left prefrontal rTMS at 120% resting MT, 10 Hz, 5 s on, and 10 s off and for a mean of 6800 stimuli per session (34,000 stimuli per week), these higher rTMS doses were well tolerated without significant adverse effects or adverse events. All measured dimensions showed improvement, with many showing improvement in 1-2 weeks. Of perhaps most importance, suicidal ideation diminished in 67% of the patients after just 1 week
2013	Mantovani et al.[33]	Twenty five patients compared with matched controls. Cases received 1800 stimuli/day, 1-Hz, at 110% of RMT; Five times/week. At 4 weeks, response rate for panic disorder was 50% with active rTMS and 8% with sham. After 8 weeks of active rTMS, response rate was 67% for panic and 50% for depressive symptoms. A longer course of treatment resulted in better outcomes for both panic disorder and major depression
2013	Hizli Sayar et al.[34]	Prospective open study. 65 depressed elderly patients, 6 days/week, for 3 weeks. 100% RMT, 25 Hz, 2 s duration, 20 times with 30 s interval. Total 1000 pulses. Treatment safe and effective
2017	Bulteau et al.[35]	Randomized, controlled, double-blind, single-center study with two parallel arms. Intermittent theta burst, 80% MT, 50Hz, burst frequency 5Hz, 3 pulses, number of bursts 3, cycle time 10 s, number of cycles 20, 600 pulses. Ongoing study
2011/2017	FDA (USA)[36] 2011 and RC Psych (UK)[37]	120% above MT, 10 Hz, pulse duration: 4 s, 10 pulses per second, 26 s off, number of trains 75, 3000 pulses, total actual treatment time: 37.5 min
2016	Wilson and St George[38]	The authors reviewed existing protocols and their efficacy and called for uniformity and standardization of the procedure. They also acknowledged rapid advances and advocated collaing the data
2018	Blumberger et al.[7]	Randomized, multicenter, double blind clinical trial in which 205 participants received 10 Hz rTMS and 209 participants to receive iTBS. After 4-6 weeks of treatment both the groups had improved depression scores and there was no significant difference between the two groups implying that iTBS burst offers advantage in terms of time per patient

The protocols for delivering TMS are gradually evolving and keeping pace with technology and research in biosciences. The table shows evolution and refinement of protocols for TMS. It is noteworthy that latest protocols favor the role of TMS in TRD and are less time consuming. Dominant (left) DLPFC is the preferred site for stimulation in most studies. MT - Motor threshold; RMT - Resting MT; TMS - Transcranial magnetic stimulation; rTMS - Repetitive TMS; TRD - Treatment resistant depression; iTBS - Intermittent theta burst stimulation; DLPFC - Dorsolateral prefrontal cortex

Indications/applications of transcranial magnetic stimulation

What initially started as a purely noninvasive diagnostic tool is slowly emerging as an effective tool in the hands of a harried clinician dealing with intractable and chronic psychiatric and neurological conditions. The discussion below is restricted to the psychiatric applications, especially for TRD.

Investigational/diagnostic applications

Initially, the role of TMS was restricted to experimental brain research to localize motor and sensory areas. When combined with functional magnetic resonance imaging, positron-emission tomography or single-photon emission computed tomography, TMS indicates the functional integrity of intracortical neuronal structures and gives information about the conduction along various fibers, the function of nerve roots and peripheral motor pathways. It can also help in localizing level of the lesion within the nervous system in conditions such as stroke, injury, or demyelination/sclerosis.[39]

Therapeutic uses

TMS is slowly gaining popularity as a useful therapeutic tool in many psychiatric disorders though FDA has cleared its role in Major unipolar depression and obsessive-compulsive disorder only. This paper focuses primarily on current evidence supporting its role in the treatment of unipolar depression. The findings are summarized in Table 3. George and Wassermann[40] first reported the benefits of daily rTMS to left PFC in resistant depression which were further corroborated by Pascual-Leone et al.[41] in 1996 and Liu et al.[42] In their meta-analysis, the pooled rates for rTMS group were 46.6% and 22.1% for response and remission, respectively. The pooled odds ratio was 5.12 (95% confidence interval; 2.11–12.45, P = 0.0003). The number needed to treat in their analysis was 3.4. However, there was marked variability in terms of number of treatments and the stimulus intensity. Padberg et al.[43] provided evidence of relation between antidepressant efficacy and stimulation intensity. They found clinical improvement at 100% RMT as compared to sub-threshold at 90% RMT. Avery et al.[44] reported results of their double-blind sham-controlled RCT done on 68 TRD patients (35 in rTMS and 33 in the sham arm). Patients with medication-resistant depression were randomized to receive 15 sessions of active or sham rTMS delivered to the left DLPFC at 110% RMT. Each session consisted of 32 trains of 10 Hz rTMS delivered in 5-s trains. They concluded that by adjusting the protocol to therapeutic levels in terms of stimulation intensity, pulse frequency and number of treatments, rTMS is an effective strategy to treat-resistant depression. The probability of adverse effects besides clinical improvement was the focus of research by O’Reardon et al.[45] They found a significant reduction in HAMD score after 4 weeks of treatment with rTMS and reported minimal side effects such as scalp pain (35%) and local discomfort (10%). These effects were transient and resolved spontaneously within a few minutes or hours. Long-term efficacy of rTMS in the prevention of recurrence and relapse has been topic of intense debate. Dunner et al.[46] studied long-term effectiveness of TMS across many sites and concluded that TMS demonstrates a statistically and clinically meaningful durability of acute benefit over 12 months of follow-up. Cost-benefit ratio was another area of research, which warranted systematic analysis. Nguyen and Gordon[47] concluded that rTMS was statistically superior and cost-effective antidepressant for patients with TRD. However, web results in this area did not reveal many references. In brief, research about long-term efficacy and cost-benefit ratio is sparse and continues to be hotly debated, especially in third world countries where resources are limited. Regarding who may benefit more from rTMS therapy, Fregni et al.[48] concluded that rTMS may be most suited for younger and less treatment-resistant patients. Head-to-head comparison of rTMS with ECT was done by Slotema et al.,[49] who reported that ECT was superior to rTMS in the treatment of depression (mean weighted effect size −0.47, P < 0.004). However, comparative acceptability and side effect profile were superior for rTMS. Chen et al.,[50] conducted head-to-head comparison of ECT and rTMS as augmentation strategy for TRD. They included 25 studies with 1288 individuals with MDD. They reported that ECT was more efficacious than bilateral-PFC rTMS, however, differences were not statistically significantly. Razza et al.[51] reported that though there may be placebo response to rTMS in depression trials, pooled data reveal that current protocols achieve 29%–49% response and 19%–34% remission in TRD, indicating intermediate efficacy between medication and ECT. In 2014, the International Federation of Clinical Neurophysiology gave guidelines for therapeutic use of rTMS.[13] They gave three levels of evidence for the efficacy of rTMS in various neuro-psychiatric disorders, i.e., level A (definite efficacy) was for antidepressant effect of HF-rTMS of left DLPFC, level B (probable efficacy) for antidepressant effect of LF rTMS of the right DLPFC and HF-rTMS of the left DLPFC for the negative symptoms of schizophrenia; whereas level C (possible efficacy) was for LF-rTMS of the left temporoparietal cortex for auditory hallucinations in Schizophrenia. The most recent approval by US FDA for rTMS has been for obsessive-compulsive disorders in Aug 2018.[52]

Table 3

Summary of evidence for therapeutic uses of repetitive transcranial magnetic stimulation

Author	Methodology	Year of publication	Measures	Outcome	Additional remarks
Pascual-leone et al.[41]	Multiple cross-over, randomised placebo controlled trial	July 1996/The Lancet	HDRSBQ	Significant improvement in HDRS and BQ scores after real rTMS over left DLPFC11/17 patients showed pronounced improvement that lasted for 2 weeks after 5 days of daily rTMS sessions	No patient experienced any significant undesirable side-effects
Liu et al.[42]	Meta-analysis	2014/BMC Psychiatry	Pooled OR NNT	Pooled response and remission rate for the rTMS and sham group was 46.6% and 22.1%, respectively; pooled OR was 5.12 (95% CI 2.11-12.45, Z=3.60, P=0.0003), NNT was 3.4Pooled SMD of change from baseline was 0.86 (95% CI 0.57-1.15, Z=5.75, P<0.00001)	rTMS was a safe strategy with relatively low adverse events and low dropout rate
Padberg et al.[43]	Parallel design controlled study	2002/Neuro psychopharmacology	HDRS MADRS Duration of hospital stay	HRSD decrease by 30% after 100% MT rTMSFor MADRS scores, the antidepressant effect significantly increased from sham rTMSover 90% MT rTMS to 100% MT rTMS (P<0.05)rTMS at MT significantly reduced hospital stay and the number of AD trials	No severe side effects of rTMS were observed
Avery et al.[44]	Double blind sham controlled RCT	2006/Biol Psychiatry	HDRS	Response and remission rates for rTMS group were 30.6% (11/35) and 20% (7/35), respectively, and for sham group were 6.1% (2/33) and 3% (1/33), respectively.The differences were statistically significantly (P<0.008) for response and (P<0.033) for remission	No seizures were associated with active TMS. No subject dropped out because of pain or discomfort of the TMS treatment
O’Reardon et al.[45]	Double-blind, multisite study, sham controlled RCT	2007/Biol Psychiatry	HDRS MADRS CGI-S	Response rates were significantly higher with active TMSRemission rates were approximately twofold higher with active TMS	Scalp discomfort and pain with (mild-moderate) and diminished in incidence after the first treatment week
Dunner et al.[46]	Multisite, naturalistic, observational study	2014/J Clin Psychiatry	CGI-SIDS-SR PHQ-9	Statistically significant reduction in mean total scores on CGI-S, IDS-SR and PHQ-9 scales sustained throughout follow-up (P<0.0001)	No control group
Nguyen and Gordon[47]	A 3-year Markov microsimulation model with 2-monthly cycles	2015/value in health	Incremental cost per QALY	Although both pharmacotherapy and rTMS are clinically effective treatments for major depressive disorder, rTMS is shown to outperform antidepressants in terms of cost-effectiveness for patients who have failed at least two adequate courses of antidepressant medications
Fregni et al.[48]	Systematic review (6 studies)	2006/International Journal of Neuro psychopharmacology	HDRS	TMS antidepressant therapy in younger and less treatment-resistant patients is associated with better outcome	Most common adverse effects were headache, neck pain, and scalp burnNo report of seizures
Slotema et al.[49]	Meta-analysis	2010/Journal of Clinical Psychiatry	Standardized mean effect sizes of rTMS versus sham	DepressionMean weighted effect size of rTMS versus sham was 0.55 (P<0.001)ECT >rTMS in the treatment of depression (mean weighted effect size - 0.47, P=0.004)	Side effects were mild, yet more prevalent with high-frequency rTMS at frontal locations
Chen et al.[50]	Double-blind sham controlled RCT	2013/Neuropsychiatric Disease and Treatment	HDRS	Active rTMS group maintained their improvement as measured 1 month after completion of the rTMS protocol	Small sample size (10 in each arm)
Razza et al.[51]	Systematic review and meta-analysis	2018/Progress in Neuro psychopharmacology and Biological Psychiatry	Hegdes g Placebo response in rTMS	Placebo response was large (g=0.8, 95% CI=0.65-0.95, P<0.01)	Placebo response a part of therapeutic response to rTMS
Lefaucheur et al.[13]	Evidence based guidelines on therapeutic use of rTMS	2014/Clinical Neurophysiology	Levels of evidenceLevel A (definite efficacy)Level B (probable efficacy)Level C (possible efficacy)	Level A: Antidepressant effect of HF-rTMS of DLPFCLevel B: Antidepressant effect of LF rTMS of the right DLPFC, HF-rTMS of the left DLPFC for the negative symptoms of schizophreniaLevel C: LF-rTMS of the left temporoparietal cortex auditory hallucinations	Guidelines by International Federation of ClinicalNeurophysiology
US FDA Aug 2018[52]	Sham controlled RCT	US FDA press releaseApproved marketing of Brainsway dTMS for obsessive-compulsive disorder	YBOCS	38% in dTMS group responded versus 11% in sham group. Difference in response was clinically significant	Brainsway dTMS with 5 cm depth of penetration

TMS - Transcranial magnetic stimulation; rTMS - Repetitive TMS; LF - Low-frequency; dTMS - Deep TMS; BQ - Beck questionnaire; DLPFC - Dorsolateral prefrontal cortex; OR - Odds ratio; NNT - Number needed to treat; CI - Confidence interval; SMD - Standardized mean difference; MT - Motor threshold; ECT - Electroconvulsive therapy; RCT - Randomized controlled trial; HF - High-frequency; HDRS - Hamilton depression rating scale; MADRS - Montgomery-asberg depression rating scale; HRSD - Hamilton rating scale for depression; AD - Anti-depressant medication; CGI-S - Clinical Global Impression- severity scale; IDS-SR - Inventory of Depressive Symptomatology (Self-Report); PHQ-9 - Patient health Questionnaire-9; QALY - Quality Adjusted LifeYear; US FDA - United States Food and Drug Administration; YBOCS -Yale-Brown Obsessive Compulsive Scale

Use of repetitive transcranial magnetic stimulation in special population

Although a lot of data and best practice recommendations for TMS usage in adults are largely available, there is a dearth of similar data for the pediatric population. However, its practice in children continues to grow. Its minimal risk, excellent tolerability and increasingly sophisticated ability to interrogate neurophysiology and plasticity make it an easy technology for use in pediatric research, with future extension into therapeutic trials. While adult trials show promise in using TMS as a novel, noninvasive, nonpharmacologic diagnostic and therapeutic tool in a variety of neurological disorders, its use in children is only just emerging.[5354] Its use in pregnancy is safe and effective and pregnancy per se is not a contraindication.[55] rTMS was well tolerated and found to be statistically and clinically effective in pregnant patients with TRD. It may be preferred choice of treatment in the elderly population owing to the lack of cognitive side effects and very little chance of drug interactions. Cognitive impairment has been researched the most in this population and evidence so far suggests that TMS may, in fact, have therapeutic benefits.[56] However, additional research that specifically includes older subjects is needed to replicate findings and to optimize treatment protocols for this population.

Other psychiatric indications of transcranial magnetic stimulation

There are reports of the role of rTMS in chronic schizophrenia in controlling intractable hallucinations and negative symptoms. The US FDA and NICE guidelines (UK) have included rTMS a therapy for treating migraine.[5758] There are also reports of its role in treatment of anxiety disorder like PTSD and substance use disorders. However, detailed description of these indications is beyond the purview of this article and reader is advised to refer to other sources of information.[5960]

CONCLUSION

The field of diagnostics and therapeutics in psychiatry is still in a state of flux. As research in neurosciences moves at a rapid pace, there is a need to translate the findings into treatment methods. rTMS is a big step in this direction and offers a therapeutic approach without serious and long-lasting side effects. It is slowly emerging as an effective tool in managing TRD, though evidence in favor of its role in other psychiatric conditions is still sparse. It is safe and well tolerated by most patients. There is a need to develop well-standardized protocols for its application and to establish it as an affordable therapeutic tool.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.