TMS in Depression

Personalizing TMS therapy for the individual patient

At Nexstim we are using our decades of scientific research to help treat depression noninasivley and without the use of drugs. As the world’s leading company combining TMS with 3D imaging, we enable personalized TMS treatment with unsurpassed accuracy and precision.

Bringing accuracy and precision to TMS therapy for depression

Transcranial magnetic stimulation (TMS) stimulates the brain using small electrical fields. A coil resting against the patient’s head communicates directly with the underlying neurons of the brain. The Nexstim NBT® System uses TMS with sophisticated navigation tools to visualize the location, orientation and magnitude of the maximum stimulating E-field induced when the TMS coil is activated. We call this SmartFocus® TMS.

Choose your Location

A non-drug option, SmartFocus® TMS only influences the brain and doesn’t impact the rest of the body’s chemistry. In fact, TMS speaks the same language as the brain—electricity.

Targeting the left DLPFC

TMS is targeted to a region of the brain called the left DLPFC (dorso-lateral pre-frontal cortex) which is at a depth easily accessible by the normal strength of magnetic field emitted by TMS coils. It is believed that the left DLPFC is a window into a brain network including the subgenual cingulate and that stimulation of the left DLPFC has effects on the brain’s deeper limbic system. Brain imaging studies (fMRI) have shown connectivity between the stimulation site and the subgenual is a predictor of response to TMS in major depressive disorder (MDD)**. PET imaging studies in patients diagnosed with MDD have shown lower metabolism, compared to controls, in their left DLPFC regions, which supports the concept of using TMS as a therapy to increase the excitability of the left DLPFC. 

The left DLPFC has been validated as an efficacious target in several large, randomized controlled trials. The effects of TMS treatment have been shown to be dependent on the left DLPFC region receiving a sufficient “dose” of E-field each session and the sessions being repeated almost daily over many weeks. The observed effects of TMS suggest that the part of the mechanism behind TMS is neuroplasticity, the brain responding to the TMS treatment by “re-wiring” its own circuits.

**Weigand A et al. Prospective Validation That Subgenual Connectivity Predicts Antidepressant Efficacy of Transcranial Magnetic Stimulation Sites. Biol Psychiatry. 2017 Nov 10

The Nexstim NBT® System uses TMS with sophisticated navigation tools to visualize the location, orientation and magnitude of the maximum stimulating E-field induced when the TMS coil is activated. We call this SmartFocus™ TMS .

Researchers have shown that the location of the E-field in the brain is dependent on both the conductivity as well as the geometry of the underlying tissues.

Calculating the E-field location requires sophisticated modelling of tissue geometry. Nexstim uses an algorithm based on mathematically modelling the human brain as over 40,000 spheres—taking into account the brain’s shape as well as the effects of cerebrospinal fluid, grey matter and white matter on the induced E-field.

The Nexstim multi-sphere model of the brain has been scientifically-validated to accurately determine the location and orientation of the maximum induced E-field—and is the foundation for the FDA-clearance of our technology for pre-procedural planning, used in neurosurgery.**

** Krieg S (Ed.), Navigated Transcranial Magnetic Stimulation in Neurosurgery, Springer International Publishing, 2017

Personalizing the stimulation level for the individual patient

The effects of stimulation are always dependent on the intrinsic excitability state of the patient’s brain and cortex. This state is unique for each patient but can easily be measured by TMS. 
Once the motor strip has been identified, TMS is applied to the hand motor representation area, the “hand knob” with varying intensities to quantify the patient’s resting motor threshold, RMT. A patient’s RMT is defined as the minimum stimulation intensity capable of generating an MEP in 50% of given stimuli. Nexstim systems use an algorithm to ease the calculation.

It is important to carefully map for the optimal hand knob location using all the dimensions available for moving the coil, especially rotation. The goal of this mapping is to locate the site most sensitive to stimulation, otherwise the patient’s true resting-state cortical excitability cannot be determined. If the patient’s motor threshold calculation is based on measurement at an erroneous location, there is the subsequent danger of over-stimulating the cortex in therapy, as well as causing the patient unnecessary discomfort or pain.

rTMS therapy for depression is normally given at 120% of RMT. Cortical motor mapping can normally be performed at 110% of RMT, or higher.

Clinical efficacy

The clinical efficacy and safety of 10 Hz rTMS stimulation of the left dorsolateral prefrontal cortex in the treatment of MDD has been studied in a sham-controlled multicenter clinical trial (see O’Reardon et al.*) with an overall population of 301 patients meeting DSM-IV criteria in the diagnosis of MDD. MDD episode as defined by DSM-IV involves the nearly daily presence during the same two-week period of five or more of the following symptoms:

  • Depressed mood most of the day as indicated by either subjective report or observation made by others
  • Markedly diminished interest or pleasure in all, or almost all, activities most of the day
  • Significant weight loss or weight gain, or decrease or increase in appetite
  • Insomnia or hypersomnia
  • Psychomotor agitation or retardation
  • Fatigue or loss of energy
  • Feelings of worthlessness or excessive or inappropriate guilt
  • Diminished ability to think or concentrate, or indecisiveness
  • Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.

Efficacy of the treatment was established in retrospective analysis (see Lisanby et al.**) for the outpatient group (164 patients, aged 18-70 years) who had one adequate antidepressant treatment in the current episode but failed to achieve satisfactory improvement and were moderately to severely symptomatic. Efficacy of treatment, sham or active stimulation, was measured in total change in MADRS score at 2, 4 and 6 weeks into treatment when compared to baseline level (see the figure).

*O’Reardon et al., Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry 2007 Dec 1; 62(11): 1208-1216. Epub 2007 Jun 14. PubMed PMID: 17573044.

**Lisanby et al., Daily left prefrontal repetitive transcranial magnetic stimulation in the acute treatment of major depression: clinical predictors of outcome in a multisite, randomized controlled clinical trial. Neuropsychopharmacology. 2009 Jan; 34(2):522-34. Epub 2008 Aug 13. PubMed PMID: 18704101.



FDA Cleared and CE Marked for iTBS as well

Each depression treatment session ranges between 3–37 minutes approximately, depending on the decided treatment protocol: Nexstim NBT® System with SmartFocus® TMS is FDA cleared and CE marked for the 50Hz 3–minute theta burst protocol as well as for the 10Hz protocol.

SmartFocus® TMS — a new noninvasive, non-drug therapy for depression.


SmartFocus® TMS creates a 3D model of the patient’s brain from an MRI head scan. With the patient comfortably seated, the MRI is co-registered to the patient’s head using the tracking system with Nexstim’s unique forehead tracker. When resting the coil against the patient’s head, the system now visualizes the coil and E-field overlaid on the 3D model of the brain. As the coil is moved, the magnitude (V/m) and orientation of the E-field relative to the cortex are dynamically calculated and displayed in real time.


Place EMG electrodes over hand muscles. Using single-pulse TMS to accurately locate the primary motor area, the SmartFocus® TMS software quickly guides the operator to determine an optimized intensity of the TMS dose for the patient’s individual cortical excitability.


The published, science-based algorithm allows accurate and reliable identification of the left DLPFC in the brain — the validated target in the cortex for treating depression.


The coil is aligned to the target and then locked in place for the treatment session. The system delivers the prescribed dose of TMS pulses while the system operator monitors treatment precision from on-screen visual feedback — in real time.


The system automatically stores the target-finding, dosedefining and other settings needed to personalize the TMS therapy for the patient. In subsequent treatment session, SmartFocus® TMS guidance software helps the system operator ensure the patient receives the same optimized dose at the same location and in the same orientation.

Same dose, same location—every time.

After 6 months of clinical use, we are even more convinced that our decision to go with Nexstim for treatment of our patients with refractory depression, was the correct one.

Randall Solomon, MD, Island Psychiatry, New York, United States

We have been very impressed with the navigated Nexstim NBT® System which is clearly an advance on the brain stimulation systems we have used previously during the past 20 years.

Dr. Andreas Winkler, Neurologist, Head of the Neurological Department, Klinik Pirawarth, Austria

Use of navigated rTMS has the potential for a significant increase in treatment efficacy compared to non-navigated rTMS. Navigation is specifically helpful  for target stimulation over the DLPFC, but also to stimulate the various regions of the motor cortical area with anatomical and functional relevance.

Prof. JP LEFAUCHEUR, Henri Mondor University Hospital, Clinical Neurophysiology, Creteil – Paris Est, France

Indications for use and patient safety


FDA IFU: Nexstim Navigated Brain Therapy (NBT) System 2 is indicated for the treatment of Major Depressive Disorder in adult patients who have failed to achieve satisfactory improvement from prior antidepressant medication in the current episode.

CE mark : Nexstim Navigated Brain Therapy System for depression is intended to be used for treatment of major depressive disorder (MDD) by targeting and delivering noninvasive repetitive TMS stimulation to the patient's dorsolateral prefrontal cortex.


  1. Patients with non-removable conductive, ferromagnetic, or other magnetic-sensitive metal anywhere in the head or within 30 cm (12 in) of the stimulation coil. Examples include cochlear implants, implanted electrodes or stimulators, aneurysm clips or coils, stents, bullet fragments, ocular implants, and stents.
  2. Patients who have an active or inactive implanted device (including device leads), including deep brain stimulators, cochlear implants, cardiac pacemakers, and vagus nerve stimulators. Contraindicated use could result in serious injury or death.
  3. Patients with increased intracranial pressure or patients with intracardiac lines, intravenous pumps, or dose calculators. 

Failure to follow these restrictions could result in serious injury or death.


Seizures (convulsions): Cortical magnetic stimulation runs the risk of inducing seizures; although they are rare. Under ordinary clinical use, the estimated risk of seizure is approximately 1 in 30 000 treatments (0.003%) or 1 in 1000 patients (0.1%). 

Headache: The most common side effects reported during clinical trials are mild headache (~50% of TMS treatment group) and scalp pain or discomfort (35.8%). In general, headache and pain on the stimulation site have been generally mild to moderate and occurring less frequently after the first week of treatment. The reason for headache may be the tension of scalp and neck muscles due to an uncomfortable and stressful situation.

Muscle Twitching:  You may feel twitches in the muscles of your arm, leg or face during the magnetic stimulation. This is a common sensation but not hazardous. The twitches will stop when the magnetic stimulation stops.

Skin Irritation:  There is a small risk of mild skin irritation at the location where the muscle electrode sensors have been placed, but this usually consists of minor redness that will go away quickly after they are removed.

Changes in hearing:  The loud “click” produced by the TMS stimulator can cause temporary hearing changes following treatment.  This is prevented by wearing soft foam ear plugs during treatment. No problems with hearing due to TMS have ever occurred when earplugs have been properly worn


There is no evidence that single therapy sessions would improve mood.  rTMS treatment effects in reducing depression are temporary, and patients may need to continue other forms of depression therapy. Relapse into depression is likely without follow-up treatment. Notify your doctor in case of worsening depression or suicidality. 


All patients must be screened for the characteristics listed in this section and excluded without clear benefit or compelling clinical reason.
The safety and effectiveness of Nexstim TMS treatment has not been established in the following patient populations:

  • Younger than 22 years or older than 70 years
  • Suicide plan or recent suicide attempt
  • History of concurrent use of electroconvulsive therapy (ECT) or vagus nerve stimulation (VNS)
  • Depression secondary to a general medical condition or substance-induced
  • Seasonal affective disorder
  • History of substance abuse, obsessive compulsive disorder, or post-traumatic stress disorder
  • A psychotic disorder, including schizoaffective disorder, bipolar disorder, or major depression with psychotic features
  • History of increased intracranial pressure or head trauma
  • Cardiac pacemakers, implantable cardioverter defibrillators, ocular implants, deep brain stimulators, vagus nerve stimulators, implanted medication pumps, intracardiac lines, or significant cardiac disease
  • Pregnant or nursing

NBT System stimulation protocol for the treatment of major depressive disorder (MDD)

Pulse timing


10 Hz bursts of 40 pulses (one burst is of 4 s duration)
One burst every 30 s, interval of 26 s
Total pulses in a sequence: 3,000
Total sequence duration:  18.8.-37.5 min


50 Hz bursts of 3 pulses
5 burst per second, duration 2 seconds, 8 seconds interval
Total pulses in a sequence: 600
Total sequence duration:  3min 17s

Stimulation intensity

The intensity of the output of the stimulator should be set by operator to 120 % of the resting motor threshold (rMT) of the individual patient’s cortex. A patient’s rMT is determined in a two-step process.
First, single-pulse mapping of the primary motor cortex is used to find the coil location and orientation—the “hotspot”— giving the maximal EMG amplitude in the APB-muscle abductor pollicis brevis (APB) of the left thumb.
Second, targeting the hotspot, the operator uses Nexstim’s proprietary software-assisted stimulation sequence to determine the patient’s rMT. The NBT System software defines the rMT as the lowest level of stimulator output needed to elicit a >50 µV MEP response (peak-to-peak) in the muscle, as observed on EMG, 50% of the time from 10 stimuli.
It is important that the patient is fully relaxed during rMT finding and does not voluntarily activate (move) the hand or arm muscles.

Re-measurement of motor threshold

Re-measurement of rMT may be required if the treating physician suspects that the patient’s cortical excitability has changed. Since the patient’s individual hotspot is one of the patient’s vital parameters stored by the NBT System, rMT re-measurement is a rapid procedure offering a reliable result for intra-patient comparison.

Caution on special conditions and populations

The safety and effectiveness of the NBT System has not been established in the following patient special populations or clinical conditions.

  • Patients who have had no prior antidepressant medication failure.

Special Populations

  • Patients who have a suicide plan or have recently attempted suicide.
  • Patients with seasonal affective disorder.
  • Patients younger than 22 years-of-age or older than 70 years-of-age.
  • Patients with a history of substance abuse, obsessive compulsive disorder, or post-traumatic stress disorder.
  • Patients with a psychotic disorder, including schizoaffective disorder, bipolar disease, or major depression with psychotic features.
  • Patients with neurological conditions that include a history of seizures, cerebrovascular disease, dementia, movement disorders, increased intracranial pressure, having a history of repetitive or severe head trauma, or with primary or secondary tumors in the CNS.
  • Patients with metal in or around the head, including metal plates, aneurysm coils, cochlear implants, ocular implants, deep brain stimulation devices and stents.
  • Patients with vagus nerve stimulators (VNS) or implants controlled by physiologic signals, including pacemakers, and implantable cardioverter defibrillators.
  • Patients with major depressive disorder who have failed to receive clinical benefit from electro-convulsive therapy (ECT) or VNS.
  • Patients who are pregnant or nursing.