According to the World Health Organization (WHO), depression is projected to become the number one global disease burden by 2030. Present-day statistics suggest that depression affects over 350 million people worldwide. Among those who are depressed, seeking professional psychiatric treatment is often helpful.
An estimated 66% of all individuals who seek treatment are able to experience symptomatic relief as a result of prescription antidepressants (e.g. SSRIs, SNRIs, etc.). Another percentage of individuals may find that adding psychotherapy to the equation provides synergistic symptomatic relief, reducing depressive symptoms to a greater extent than a standalone antidepressant. Unfortunately, a large percentage of individuals aren’t able to reduce their depression no matter how many science-based treatments are pursued.
These individuals may even attempt to overcome depression logically with lifestyle changes, or resort to exploring natural cures for depression. For certain individuals, no matter how many attempts are made to treat depression, the genetic deck may be stacked against them. This inevitably results in “battle fatigue” in which a person is tired of trying new treatments because they’ve yet to find anything that works.
Even worse, they may end up experiencing learned helplessness, believing nothing will ever work. Fortunately, neuroscientists, psychiatrists, psychologists, and pharmaceutical companies are constantly devising new, high tech treatments for depression. One such strategy utilizes high-powered magnets to electrically stimulate specific regions of the brain to improve mood. This technique called transcranial magnetic stimulation (or “TMS”) is considered an effective non-pharmacological treatment for depression.
What is Transcranial Magnetic Stimulation (TMS)? (How It Works)
Transcranial magnetic stimulation (TMS) involves the usage of a high-intensity magnetic field generator (in the form of a “coil”) to emit intermittent [small-scale] electrical currents. These currents are capable of stimulating neurons up to 2.5 cm beneath the cortex. Each pulsation is thought to promote depolarization of neurons, prompting the release of neurotransmitters.
It is believed that specific neural pathways connecting the prefrontal cortex with the limbic system are also indirectly activated as a result of TMS therapy. Changes in blood flow and cerebral glucose metabolism have been recorded by neuroimaging scans following TMS therapy. It is the combination of the neurotransmitter release, limbic activation, and altered blood flow plus glucose metabolism – that contribute to mood improvement.
TMS Coils
To target a particular region for stimulation, a coil is placed above the specific region of the brain that will be targeted with treatment. There are several types of coils that can be used in transcranial magnetic stimulation. Coil types can differ based on materials, shape of the coil, and types of pulsations they emit. Certain coils are thought to be filled with air (eliciting no effect), while others may contain a core full of a solid material to enhance the delivered effect by generating greater amount of energy within the magnetic field.
The standard coil used in TMS is a rounded coil, but the coil can be tweaked in dimensions to provide more potent penetration beneath the surface of the cortex. The standard TMS coils are able to impact neurons within the range of 1.5 cm to 2.5 cm, whereas a coil shaped differently may exceed the 2.5 cm. H-coils are commonly used for deep transcranial magnetic stimulation, penetrating neurons much deeper than standard TMS.
Neurons emit an action potential
As the pulsations of the magnetic field are delivered to a specific area of the brain, neurons become depolarized or hyperpolarized, triggering neurons to emit an action potential (and release neurotransmitters). This stimulation is thought to facilitate mood improvement among those who are severely depressed. There are a number of different ways in which the mood improvement may occur as a result of TMS.
Targeting the left vs. right prefrontal cortex
In particular, it is thought that stimulation of the left prefrontal cortex with rTMS excites surface-level neurons, ultimately increasing activation in this region to boost mood. Those with depression often display hypoactivation (underactivation) of the left-prefrontal cortex, and rTMS gives various neurons and circuitry a much-needed “jump start.” Another TMS administration protocol for depression is to target the right prefrontal cortex with low frequencies.
This may provide benefit to those who have overactive right prefrontal activity contributing to their depressive symptoms. The lower frequencies of stimulation tone down activity in the right prefrontal cortex and simultaneously tone down the severity of a person’s depression.
Note: Despite the fact that the procedure is called transcranial “magnetic” stimulation, this name is somewhat misleading due to the fact that the mechanisms associated with its effect are electrical (as opposed to magnetic).
History of Transcranial Magnetic Stimulation (TMS)
The concept of electromagnetic induction was initially discovered in 1831 by Michael Faraday. By 1910, Silvanus P. Thompson had attempted to stimulate his own brain with magnetic fields. In the early days of magnetic brain stimulation, it was thought that the devices used to stimulate the brain weren’t potent enough to produce substantial change.
In order for TMS to be effective, it is necessary to generate large magnetic fields that can quickly change. By 1976, the University of Sheffield was attempting to stimulate nerves using currents of a short magnetic pulses. A method of transcranial stimulation was initially suggested by Merton and Morton in 1980, involving direct electrical current on the scalp.
In the early 1980s, scientists were able to stimulate peripheral nerves, and by 1985 transcranial magnetic stimulation was demonstrated by Anthony Barker et al. It was thought that TMS could be used to help diagnose neurological pathologies and as a form of therapy.
Transcranial Magnetic Stimulation for Depression (Scientific Research)
Research investigating the efficacy of TMS for depression began in the early 1990s, and has continued throughout present-day. Below is a synopsis of the cumulative scientific research of TMS for depression. While there are several studies spanning from 2002 to 2006 that question the efficacy of TMS, an overwhelming majority of research suggests that rTMS targeting the left dorsolateral prefrontal cortex at a high-frequency is an effective treatment for depression.
2014: A study published in 2014 noted that a previous trial had been conducted in 48 individuals with treatment-resistant depression. The trial was controlled with a “sham” TMS and analyzed the efficacy of 5 Hz rTMS (repetitive transcranial magnetic stimulation) across the left and right dorsolateral prefrontal cortex. Results indicated that individuals derived the greatest antidepressant benefit from targeting the right dorsolateral prefrontal cortex with rTMS.
Researchers analyzed these results and attempted to understand how neuropsychological function changed compared to baseline. Specifically, they analyzed the following: depression severity, changes in depression with treatment, rTMS compared to “sham” TMS, laterality of stimulation, and rTMS-laterality interaction. The right dorsolateral PFC targeting of rTMS improved language function significantly compared to the “sham.”
Furthermore, the rTMS targeting the right dorsolateral PFC enhanced visuospatial performance and episodic memory significantly compared to the rTMS targeting the left dorsolateral PFC. The results indicated that despite improvements in neuropsychological abilities, these were unrelated to relief from depressive symptoms. Authors concluded that rTMS targeting the right dorsolateral PFC may provide simultaneous cognitive enhancement and mood improvement among those with depression.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24968008
2012: A study published in 2012 noted that there haven’t been many studies analyzing the efficacy of TMS in real-world practices. Researchers focused on 42 locations practicing TMS, treating a total of 307 patients formally diagnosed with major depression. All of these individuals had refractory depression that was considered unresponsive to antidepressant treatment.
Administration of TMS therapy was based on specific instructional procedures that came with the TMS device. Baseline measures were collected, followed by more measures at Week 2, and again at Week 6. The primary measure was the CGI (Clinical Global Impressions)-Severity of Illness.
Other measures collected included a Patient-Health Questionnaire (PHQ) and an Inventory of Depressive Symptoms Self-Report (IDS-SR). Outcomes suggested that TMS treatment significantly improved depressive symptoms compared to baseline. The CGI-S assessments determined that 58% of patients had significantly improved as a result of TMS interventions.
Researchers concluded that TMS is an effective option for those who don’t respond to pharmaceutical antidepressants. An estimated 37% of patients experienced complete remission, and patient self-reports (PHQ and the IDS-SR) also revealed substantial symptomatic improvement. This is more research suggesting that TMS is a practical intervention for depression.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22689344
2011: A study published in 2011 analyzed the efficacy of rTMS as an antidepressant augmentation strategy among adolescents diagnosed with depression. Repetitive TMS was administered to 8 adolescents that were formally diagnosed with major depression and failed to respond to 2 antidepressant drugs. All 8 participants were taking a stable clinical dose of an SSRI throughout the rTMS trial.
A total of 30 rTMS sessions were completed daily, for 5 days per week over the course of 6 to 8 weeks. The rTMS was administered specifically to the left dorsolateral prefrontal cortex at 10 Hz with an estimated 3,000 stimulations per treatment. It was noted that 7 out of the 8 participants were able to complete the full 30 treatment sessions.
Results indicated that the repetitive TMS was well tolerated with no major safety concerns. Baseline levels of depression were assessed prior to the rTMS treatment with the CDRS-R (Children’s Depression Rating Scale). Scores of the CDRS-R pre-rTMS were an average 65.9 and had plummeted to an average 50.9 after 10 rTMS sessions.
After 20 sessions, depression scores had further dropped to an average of 40.1, and after 30 sessions, the average depression score was 32.6. Researchers conducted a 6-month follow-up and determined that scores were approximately 32.7 – indicating that the antidepressant benefits were sustained. While this was a small-scale study, it provides evidence suggesting that rTMS may be an effective adjunct option for adolescents with refractory depression.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21951987
2011: A paper published in 2011 documented the fact that transcranial magnetic stimulation (TMS) has been around for nearly 20 years as a treatment for depression. Authors noted that many researchers have attempted to improve upon existing TMS procedures to enhance its therapeutic efficacy. They stated that it is important to understand the specific mechanisms behind TMS’ influence on neurobiology.
Specifically, they hypothesize that TMS alters neuroendocrinological processes, neurotransmitters, and neurotrophic factors. They believe that the effects of TMS are not limited to the region targeted with stimulation, rather they suspect that TMS elicits widespread effects across the cortex; influencing a multiplicity of connected regions. Authors mentioned that the left dorsolateral prefrontal cortex seems to be a valid target for those with major depression.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21485753
2010: A publication from 2010 noted that TMS targeting the left prefrontal cortex was hypothesized as a treatment for depression since the early 1990s. Several studies have documented that TMS is more effective than a “sham” procedure, and clinical trials have lead to the approval of TMS for the treatment of depression in 2008. An additional trial sponsored by the National Institute of Health documented that 3 to 5 weeks worth of TMS significantly reduced depressive symptoms.
Despite the preliminary efficacy in the field of TMS, authors of this publication note that we still don’t understand various aspects of the practice. Many experts question the proper location to administer treatment, the mechanisms of action, the dosage, and whether the procedure should be used in conjunction with other interventions (e.g. pharmaceuticals). Authors suggest that TMS is safe without any interactions or substantial side effects.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/20977332
2009: The usage of TMS is considered safe and has improved tolerability compared to many pharmaceutical drugs and ECT (electroconvulsive therapy). That said, the efficacy of TMS among those with refractory depression has been questioned. Some studies have analyzed whether certain characteristics were likely to predict whether certain individuals derived benefit from TMS compared to others.
Researchers noted that an analysis documented that individuals experienced superior responses to TMS with a reduced number of failed antidepressant treatments. In other words, the greater the number of times a person has tried an antidepressant and failed, their odds of ameliorating depression with TMS decrease. Comparing the efficacy of TMS to antidepressants, researchers noted that randomized controlled trials of each were similar.
Moreover, it was noted that usage of atypical antipsychotics with antidepressants among those with refractory depression yielded equal efficacy rates to TMS procedures. This research suggests that TMS is likely an effective treatment for those in pursuit of non-pharmaceutical antidepressants.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19629020
2008: An open-label study was conducted to determine the short-term efficacy of TMS. Researchers designed a randomized trial that was sham-controlled with a total of 325 participants. Assessments of adverse effects were collected throughout the study, as were safety assessments measuring cognition and auditory function.
Results from the study documented that TMS treatments were administered over 10,000 times. No severe adverse reactions such as deaths or seizures were reported. Some adverse effects such as headaches and scalp irritation were documented, but less than 5% of participants discontinued the research as a result of adverse reactions.
It was evident that TMS should be considered safe, with a minimal likelihood of adverse reactions. Authors of this study suggested that TMS is likely to serve as a safe, tolerable intervention for the treatment of major depression. This bolsters other aforementioned studies highlighting the safety and efficacy of TMS.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/18232722
2008: The efficacy of TMS was tested on a specific diagnostic subtype of depression known as “vascular depression.” Vascular depression is considered depression that often emerges later in life among elderly patients. These patients are suggested to have cerebrovascular diseases, or conditions that compromise blood-flow to the brain.
Researchers set up a randomized, sham-controlled trial, administering rTMS to individuals diagnosed with vascular depression. A total of 92 individuals participated in the study, and were assigned at random to receive a sham (phony) TMS or legitimate rTMS targeting the left dorsolateral PFC (prefrontal cortex). One experiment involved administration of 12,000 pulses, whereas a second experiment involved administration of 18,000 pulses.
Results from the first experiment (12,000 pulses) indicated that individuals receiving the sham-TMS had reduced depressive symptoms of 13.6% based on the Hamilton Depression Rating Scale (HAM-D). Those receiving the legitimate rTMS experienced a 33.1% reduction in depressive symptoms. The second experiment (18,000 pulses) documented a decrease in depressive symptoms by approximately 17.5% in the sham group and 42.4% in the rTMS group (as determined by the HAM-D scale).
This suggests that TMS may be among the best antidepressants for elderly with vascular depression. Those who respond best to rTMS tend to be younger in age and have increased gray matter volume in the frontal cortex. Individuals of older age with reduced frontal cortex volume don’t derive as much benefit from rTMS.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/18316673
2006: A review published in 2006 analyzed over 25 sham-controlled trials testing the efficacy of rTMS for the treatment of depression. The researchers responsible for this review documented that administration of rTMS in the left-prefrontal region at a high frequency is superior to a sham intervention for the treatment of depression. Despite the superior efficacy when compared to a sham, the actual benefits derived from the technique were regarded as minimal.
Researchers questioned the efficacy of rTMS as well as the specific protocols being administered. They expressed concern for the fact that there are no specific rTMS parameter guidelines that are considered optimal. They also noted that rTMS isn’t yet associated with adequate therapeutic benefit.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/16683966
2003: A review conducted in the early 2000s suggested that TMS is able to effectively alter cortical physiology. The technique is considered both non-invasive and well-tolerated – with a minimal amount of adverse reactions. Authors analyzed evidence of the previous 10 years to determine the potential therapeutic benefit of using TMS for the treatment of depression.
All data collected involved TMS studies for the treatment of depression up until 2002. Results suggested that high-frequency rTMS to the left prefrontal cortex was effective for alleviation of depression. It was suspected that younger age, lack of psychotic symptoms, and certain neurological biomarkers may influence efficacy of rTMS treatment.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12727683
2003: Another study aimed to determine the efficacy of rTMS for the treatment of depression among those with bipolar disorder. Researchers specifically focused on using rTMS targeting the left prefrontal region of the brain. A total of 23 individuals with bipolar depression (12 with BP1 depression, 9 with BP2 depression, and 2 in a BP1 mixed-state) participated in the study.
All individuals were assigned at random to receive rTMS targeting the left prefrontal region or a placebo. The rTMS and/or placebo was administered daily each morning for 2 consecutive weeks. The Hamilton Rating Scale for Depression (HAM-D) and Young Mania Rating Scale (YMRS) were administered at baseline, as well as after each week of treatment.
Resulted indicated that both the rTMS and the placebo (sham-TMS) failed to improve mood among those with bipolar depression after 2 weeks. While this was a small-scale study among those with bipolar depression, it doesn’t appear to provide therapeutic benefit for depressive symptoms. That said, the technique was considered safe and did not provoke manic switching.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12656937
2003: Another paper documents that high-frequency rTMS to the left prefrontal cortex is effective as an antidepressant based on double-blinded trials. In addition, there is some evidence that targeting the right prefrontal cortex with lower rTMS frequencies may provide benefit for individuals with refractory depression. As a result, researchers investigated the therapeutic benefits of high frequency, left prefrontal TMS compared to low frequency, right prefrontal TMS.
A sham-TMS procedure was also added as a placebo control. A total of 60 individuals diagnosed with refractory depression were divided into three evenly numbered groups of 20. These groups included the: left-high frequency TMS, right-low frequency TMS, and the sham-TMS.
The Montgomery-Asberg Depression Rating Scale was administered at baseline, and then again following the 4-week experiment to gauge improvement. Results indicated that high-frequency, left prefrontal TMS and low-frequency, right prefrontal TMS are both capable of effectively treating depression over the course of 4 weeks. This provides evidence that targeting the left and right PFC with TMS can improve depressive symptoms.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/14557145
2003: A systematic review of repetitive TMS was published in 2003, analyzing its efficacy for the treatment of depression. The review incorporated randomized controlled trials comparing rTMS with a placebo (sham-TMS). A total of 14 trials fit inclusion criteria for the review, but the researchers noted that most trials were of poor quality.
The results of the systematic review revealed that rTMS was more effective than a sham-TMS for the treatment of depression for a 2 week period. Results were based on the Hamilton Rating Scale for Depression (HAM-D). Despite the increased efficacy of rTMS over the sham-TMS following 2 weeks, a post-trial follow-up (2 weeks after the experiment) documented no sustained antidepressant benefit.
Authors of the review suggested that the quality of the trials were too poor to suggest efficacy of rTMS for depression. In addition, even if rTMS was an effective antidepressant, the therapeutic effects seem to diminish within a 2-week post-treatment window.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12777338
2002: A previous review of evidence had been published in 2002, analyzing the efficacy and safety of TMS for depression. Inclusion criteria for the review was limited to randomized controlled trials that documented the therapeutic efficacy and safety of TMS for depression. Researchers were able to incorporate 16 total trials in the review, all of which were published prior to 2001.
When comparing rTMS to sham-TMS, researchers assessed degree of symptomatic improvement with the BDI (Beck Depression Inventory) and the HAM-D (Hamilton Depression Rating Scale). An analysis indicated that rTMS was no more effective than the sham-TMS. Researchers uncovered one exception to the rule of efficacy, determining that high-frequency, left dorsolateral prefrontal cortex stimulation and low-frequency right dorsolateral prefrontal cortex stimulation favored rTMS over the sham-TMS.
Comparisons of rTMS to electroconvulsive therapy (ECT) revealed that ECT was the more effective therapeutic approach for depression after two weeks of treatment. Authors of the review concluded that there was no substantial evidence to support TMS for depression. However, it was noted that there is still potential for benefit due to the fact that most samples of studies within the review were extremely small-scale.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12076483
2002: Researchers published a paper in 2002 documenting that rTMS is capable of providing modest to potent antidepressant effects (based on clinical research). They did note that there is somewhat of a dilemma in regards to choosing optimal TMS parameters for stimulation. This study specifically hypothesized that intensity of stimulation may be associated with antidepressant efficacy.
A total of 31 individuals with refractory were assigned to receive rTMS at varying degrees of stimulatory intensity. Intensity was delivered either: at motor threshold (MT), subthreshold, or low intensity of a sham-TMS. All participants were administered 10 total sessions of rTMS at a frequency of 10 Hz with 1,500 pulsations over the left dorsolateral prefrontal cortex.
Researchers noted that the antidepressant efficacy of rTMS was directly related to the degree of stimulatory intensity across all three groups. The results indicate that there is likely a relationship between intensity of stimulation and antidepressant potency. It should be noted that there may also be an unexplored, more complex relationship between administration site, frequency, and efficacy.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12377400
2001: A review published in 2001 sought to determine the efficacy of rTMS for bipolar depression and schizophrenia. Researchers included 7 controlled trials of rTMS for depression, 5 of which documented benefit of rTMS over a placebo. All trials were published prior to the year 2000.
Despite these trials documenting antidepressant efficacy of rTMS, the degree of antidepressant benefit was still unclear. Authors suggested that randomized, controlled experiments with rTMS are warranted. Furthermore, they suggest comparing rTMS directly to electroconvulsive therapy (ECT) to determine which is more effective.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/11681540
1997: A study published in the late 1990s documented early progress of TMS as a psychiatric intervention for depression. This study incorporated both published and unpublished research, ultimately suggesting that the technique is effective for the treatment of depression. Specifically, it was mentioned that high-frequency repetitive TMS yields greater therapeutic benefit than non-repetitive, lower frequency methods.
In addition, no significant unwanted side effects were provoked via TMS treatment. Authors at the time speculated that TMS was a promising new intervention to improve activity (in otherwise underactive, hypometabolic) left prefrontal regions of the brain. This provided preclinical evidence to continue investigation of TMS.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/9140635
1995: Among the earliest studies of TMS for depression was one published in the mid-1990s. Researchers at the time suspected that hypoactivation of the left prefrontal cortex promoted depressive symptoms. Since repetitive TMS is known to stimulate neurons, it was suspected that it could be used to improve mood of those with depression.
A pilot study of 6 individuals with refractory depression used rTMS targeting the left prefrontal cortex. The rTMS was administered daily and scores of depression were analyzed with the Hamilton Depression Rating Scale (HAM-D). Results indicated that HAM-D scores significantly decreased from an average of 23.8 (pre-TMS) to an average of 17.5 (post-TMS).
Perhaps most notable was the fact that an individual experienced complete remission of depression for the first time in over 3 years. Another 2 individuals experienced prominent mood improvement, which steadily increased over several weeks. Authors concluded that stimulation of the left prefrontal cortex with rTMS is safe and can be effective for depression.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/8547583
Benefits of Using rTMS for Depression
There are many potential benefits associated with using rTMS as a treatment for depression. Perhaps the most appealing benefit is that the technique can alleviate depression without any significant side effects (e.g. weight gain) that are associated with pharmaceutical approaches. Other reported benefits include: cognitive enhancement, safety, and efficacy for refractory cases of depression.
- Adjunct: Studies have shown that TMS can be used with success as an adjunct to a pharmaceutical antidepressant (e.g. SSRI). In fact, it could be speculated that the combination of the neurostimulation (via TMS) and pharmacological impact (via the medication) elicit synergistic effects. In other words, using TMS as an adjunct may provide more substantial benefit than either standalone option.
- Cascade effects: While the exact mechanisms of TMS haven’t been fully deciphered, it is believed that stimulation of one area (e.g. the left dorsolateral prefrontal cortex) affects more than that specific region. Targeting one specific region may elicit more pronounced effects in the targeted area, but may have widespread cascade effects throughout the entire brain. Variables such as neural activation, neurotransmission, neural pathways, circuitry, brain waves, and neurotrophic factors are likely altered as a result of the TMS.
- Cognitive benefit: There is preliminary evidence to suggest that TMS enhances cognitive function. Many people with depression are unable to concentrate at school and/or work as a result of severe “brain fog.” The brain fog accompanying depression is caused by a variety of complex factors, some of which may be addressed by TMS. Assuming TMS is an effective cognitive enhancer, this should improve performance at school and workplace, and theoretically should improve certain aspects of mood.
- Durability of effect: A report documented in 2013 suggests that the effect of TMS is likely to be extremely durable. Despite the lack of published clinical trials investigating the sustainability of TMS’ antidepressant effect, a 2013 American Psychiatric Association annual meeting presented findings of patients that received 4 to 6 weeks of TMS treatment and tapered off. Following the taper, they had received additional TMS with symptomatic relapses. That said, after 12-months of follow-up, 68% of patients had maintained significant symptomatic improvement and 45% were in complete remission.
- Minimal side effects: While there are some TMS side effects such as head twitching, scalp irritation, and headaches – most side effects are transient and relatively short-term. This means that if you were to receive treatment, you may have some side effects on the day of your TMS, but these would be unlikely to persist for a long duration. The side effect profile associated with TMS is favorable to pharmaceutical drugs that cause weight gain and sexual dysfunction.
- Non-pharmaceutical: Many people like the idea of taking a non-pharmaceutical drug for the treatment of their depression. Not only are there less side effects from TMS by comparison, but you don’t have to worry about filling prescriptions, taking a drug every day, and worrying about the potential long-term deleterious neurophysiological effects of daily antidepressant ingestion.
- Refractory depression: Approximately one third of users who try antidepressants find that they either do not treat their depression and/or make symptoms even worse. For these individuals, current-market pharmaceutical options are viewed as helpless. Fortunately, individuals with refractory depression often derive significant benefit from TMS which has a completely different mechanism of action. For certain people, this may be literally the only treatment that works for their depression.
- Safety: No individuals have died or experienced seizures as a result of TMS, and it is considered to be an extremely safe procedure. Obviously there are still some risks of side effects and adverse effects, but thus far no deleterious outcomes have been associated with the technique. It is unlikely to cause a worsening of depression or an increase in suicidal ideation – two outcomes that occur with medication.
Limitations associated with research of TMS for depression
There are several limitations associated with researching TMS for the treatment of depression. The major limitation is the concept of “study blinding” or the ability to convincingly facilitate a “sham-TMS” procedure. Most sham-TMS procedures are not convincing enough to mimic the real thing, which could significantly influence reported trial outcomes for depression.
- Coil types: There remain many types of coils that can be utilized via TMS for the treatment of depression. Certain coil designs may penetrate the brain deeper and be less focused in delivery, while others affect only surface-level neurons up to 2.5 cm beneath the skull. Researchers need to distinguish and focus on determining the efficacy of TMS based on specific types of coils attached to the pulse generators.
- Depressive subtypes: It is obvious that not everyone with depression has the same neurophysiological depressive signature. Some individuals may experience depression primarily as a result of an underactive left-prefrontal cortex, while others may experience depression as a result of a different degree of regional activation. Researchers should attempt to determine whether certain depressive subtypes are more or less responsive to specific TMS parameters.
- Efficacy: Most evidence indicates that TMS is an effective intervention for the treatment of depression, but the exact efficacy remains unknown. Researchers should attempt to compare the efficacy of TMS to other antidepressant modalities such as pharmaceutical drugs, and even other neurostimulation methods such as electroconvulsive therapy (ECT). Future studies should give us a better idea how the efficacy of TMS compares to other treatments.
- Mechanism of action: The mechanisms of TMS’ action aren’t fully understood and warrant further research. Understanding how TMS works should aid in the construction of new parameters for the treatment of depression. It is currently suspected that TMS stimulates neurons and circuitry, but other downstream cascade effects aren’t well-understood.
- Parameters: It is important to consider the multitude of possible TMS parameters that can be adjusted for treatment. While many studies focus on targeting the left dorsolateral prefrontal cortex with high-frequency stimulation, even the specific “high frequencies” often differ. Researchers should attempt to investigate new parameters, intensities, localizations, and protocols to understand whether certain protocols are more effective than others.
- Sample sizes: There is considerable need for larger-scale TMS studies in the future. Many studies incorporate small sample sizes of participants. Small sample sizes can often lead to false interpretations of TMS’ efficacy or inefficacy. Formal research should focus on recruitment of larger populations with hundreds of individuals to test TMS in a blinded, placebo-controlled, randomized experiment.
- Sustainability: Many trials fail to investigate the sustainability of the antidepressant effect derived from TMS. Despite the fact that certain trials have incorporated post-study follow-ups, many do not. This means that TMS may prove to be an effective treatment as long as it is continuously administered, but the effects may quickly linger, with depression quickly returning.
- Study blinding: TMS researchers have noted that it is relatively challenging to devise a “sham-TMS” procedure that is convincing enough to serve as a placebo. To fully understand whether TMS is effective, a convincing placebo-like procedure warrants development. The real procedure often triggers headaches, bodily pain, and twitching in the head. Furthermore, sham-TMS procedures can alter cerebral glucose metabolism, which could skew results. The problem is that most people receiving the sham-TMS suspect that it’s the sham rather than the real thing.
Based on the scientific evidence, is TMS effective for depression?
Yes, a bulk of evidence suggests that repetitive-TMS is an effective procedure for the treatment of depression. In particular, targeting the left dorsolateral prefrontal cortex with high frequencies seems to provide adequate stimulation to ameliorate depressive symptoms. This is likely due to the fact that many individuals with depression have underactive functioning in the left prefrontal cortex – a region associated with positive mood, logical thinking, and cognitive function.
Of the 18 studies that I was able to find that investigated “TMS” for “depression” – approximately 14 out of those 18 reported benefits and/or positive results. Most of the larger-scale trials (with greater numbers of participants) reported substantial antidepressant benefit from TMS. Assuming the study blinding with sham-TMS wasn’t overly problematic and didn’t skew results, TMS can be interpreted as a viable antidepressant option.
Do any studies question the efficacy of rTMS for depression?
It is important to mention that not all evidence fully supports the usage of TMS for the treatment of depression. A total of 4 studies spanning from 2002 to 2006 question the efficacy of the technique. A study published in 2002 reviewed 16 trials of TMS for depression compared to a sham-TMS intervention and noted that most TMS trials failed to yield an antidepressant effect.
Despite the lack of evidence in support of TMS from this review, it could be speculated that researchers had not yet determined an optimal set of parameters (e.g. stimulation of the left DL-PFC at high frequencies). Authors of this research did report that the possible benefits of TMS shouldn’t be discounted due to the fact that the sample sizes of most studies within the review were extremely small.
Another review with 14 trials published in 2003 suggested that compared to a sham-TMS, repetitive TMS was no more effective as an antidepressant intervention (based on the Hamilton Rating Scale for Depression). Despite the lack of efficacy reported, researchers suggested that inefficacy may have been related to the quality of the available studies – most were low quality. It was also mentioned that rTMS seemed to provide benefit after 2 weeks of stimulation, but the antidepressant benefits subsided 2-weeks post-treatment.
In a study testing TMS for bipolar depression, no antidepressant benefit was attained from the technique. A review from 2006 suggested that despite the superiority of rTMS compared to sham-TMS treatment for depression, its degree of efficacy as an antidepressant was minimal. While many of the trials suggesting that TMS may be ineffective had small samples and were conducted in the early 2000s, it is important to consider that the technique may be less effective than proponents suggest.
How much does TMS cost for depression?
Assuming you want to pursue TMS therapy for the treatment of depression, it’s likely to be fairly costly. This is due to the fact that there isn’t much competition, and the technology is relatively primitive. As technology continues to advanced, it is hoped that the devices drop in price and size, while increasing in efficacy.
I hope that within the next 20 years, people will be able to buy their own pre-programmed TMS device that they can self-administer rather than go into a doctor’s office. When feeling depressed, just set up your TMS machine, and send some electrical jolts through the left dorsolateral prefrontal cortex (or something like that). Currently, one session of TMS costs between $300 and $450, but some of this may be covered by your insurance.
Since many sessions are required to derive therapeutic antidepressant benefit from the technique, most people will end up paying up to $13,500 for the cumulative treatments. Most people require 30 sessions of TMS, so assuming they were each at $300 per session, you’d end up paying $9,000 and assuming they were $450 per session, you’d end up paying $13,500.
Ultimately the cost will be contingent upon the number of sessions you receive, the location, clinician, and whether your insurance covers any of the bill. Certain insurance companies still don’t support the usage of TMS due to limitations associated with the research. Other companies will cover a percentage of the treatments, possibly saving you up to half of your total bill.
Does rTMS work for everyone with depression? (Success Rate)
No, clearly the technique is not 100% effective or it would be utilized more frequently and would be covered by insurance. It is difficult to ascertain whether TMS is completely effective due to the small sample sizes in the aforementioned studies and based on the sham-TMS procedures being unconvincing. Certain people are thought to derive a greater degree of benefit from TMS including: those who are younger aged, less resistant to medications, and those with more brain volume.
How long does the antidepressant effect of rTMS last?
The exact duration of benefit associated with rTMS is subject to significant individual variation. It may depend upon specific TMS parameters (frequency, targeted region, etc.) as well as whether the individual is taking an antidepressant or using TMS as a standalone treatment. In one report of a 12 month follow-up after acute TMS treatment (4 to 6 weeks), a significant number of individuals maintained antidepressant benefit.
It should be noted that these individuals were given TMS on an “as needed” basis during the follow up when their symptoms resurfaced. Therefore it could be hypothesized that daily TMS treatment for up to 6 weeks yields long-lasting benefit, possibly for months or even exceeding a full year following cessation of TMS.
Have you tried TMS for depression?
Assuming you’ve given TMS a shot for the treatment of depression, share your experience in the comments section below. Mention the severity of your depression prior to your first TMS treatment, as well as whether it improved following a specific TMS protocol. If you derived benefit from TMS, mention the area of your brain that was targeted (e.g. the left dorsolateral prefrontal cortex), the frequencies that were applied to this area, and how long it took before you started noticing your mood improve.
Feel free to provide additional details about your TMS such as: the number of pulsations per session, the frequency of (how often) your TMS sessions (e.g. daily, bi-weekly, etc.), and the entire time span over which you were treated (e.g. weeks, months, etc.). Based on the current research, would you try TMS for the treatment of depression? Personally, I’m looking forward to the promise of Low Field Magnetic Stimulation, a technique demonstrating robust preclinical efficacy with faster action (20 minutes) than TMS.