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TMS For Anxiety Disorders (Transcranial Magnetic Stimulation)

TMS (Transcranial magnetic stimulation) is considered a non-invasive neurostimulation procedure aimed at normalizing brain activity among those with abnormal neurological function.  Individuals diagnosed with psychiatric conditions (e.g. depression) may turn to TMS for relief if standard first-line pharmacological options fail to ameliorate symptoms.  A TMS device works by using pulsed magnetic fields to generate low-grade electrical currents.

These electrical currents are then channeled to stimulate specific regions of the brain, usually the prefrontal cortex.  With daily sessions of TMS over a period of 4 to 6 weeks, individuals commonly report substantial improvements in depressive symptoms.  Although the specific mechanisms of TMS aren’t fully understood, the technique is believed to stimulate the release of neurotransmitters, upregulate hypoactive neural circuitry, and alter blood flow.

The administration of TMS for depression has been approved by the FDA since 2008.  This approval has lead people to question whether TMS could provide significant benefit for individuals with refractory anxiety.  It should be hypothesized that properly targeted TMS among those with anxiety disorders may provide significant therapeutic benefit via correcting abnormal neurological activity.

TMS for Anxiety Disorders (Scientific Research)

There is modest amount of published research analyzing the efficacy of TMS for anxiety disorders. A majority of available literature suggests that the efficacy of TMS for anxiety disorders is unknown.  Some researchers suggest that considerably more experimental trials are necessary to investigate optimal TMS parameters including: intensity, frequency, localization, etc.

Although there remains a lack of TMS research investigating its efficacy for anxiety, some studies have documented benefit for individuals diagnosed with depression and comorbid anxiety (i.e. “anxious depression”).  Another trial determined that TMS alleviated anxiety, but the anxiolytic effect was short-lived.  Perhaps most alarming is that administration of TMS to healthy animal models increases anxiety behaviors.

2014: Researchers noted that neurological dysfunction is thought to contribute to generalized anxiety disorder (GAD) as well as PTSD.  One theory is that generalized anxiety disorder is a byproduct of neurological hyperarousal in certain regions of the brain – the exact opposite of activity experienced among those with depression.  A report published in 2014 suggested that TMS may be a viable procedure for the treatment of anxiety disorders.

They note that the efficacy of TMS for conditions such as generalized anxiety disorder is poorly understood.  However, authors suggest that utilizing neuroimaging scans may help researchers determine optimal stimulatory parameters for TMS among those with anxiety.  Authors recommend adjusting parameters (pulses, frequencies, etc.) and making assessments to determine ideal TMS settings for those with anxiety.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25473719

2013: A study published in 2013 highlighted the fact that 1 out of 4 individuals with social anxiety disorder fail to respond to pharmacological interventions.  Authors suggest that idea of investigating rTMS for the treatment of social anxiety disorder.  They reviewed the literature of TMS trials among individuals diagnosed with anxiety disorders.

Collected evidence indicated that stimulation of the right prefrontal cortex with low-frequency rTMS may alleviate anxiety for certain types of anxiety disorders, but not social anxiety disorders.  The fact that certain types of anxiety improved following rTMS stimulation to the right prefrontal cortex suggests that the right hemisphere may have been overactive.  Authors speculate that TMS may be improving symptoms of anxiety as a result of correcting imbalanced hemispheric activity.

Those with anxiety are thought to have overactive right hemispheres and TMS essentially normalizes activation in this region.  Authors propose that using rTMS to target the right medial PFC with a low frequency, and the left medial PFC with a high frequency may alleviate social anxiety.  This may essentially correct imbalanced or abnormal hemispheric activation.

  • Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837365/

2013: Many individuals have depression with comorbid anxiety or anxiety with comorbid depression.  In these cases, individuals may be diagnosed with “anxious depression,” a diagnostic subtype that often responds poorly to pharmacological treatment.  Researchers in this study sought to determine whether rTMS would provide therapeutic benefit to those with “anxious depression.”

A total of 32 adults diagnosed with refractory depression were recruited for the study.  All participants were administered the Hamilton Rating Scale for Depression (HAM-D) prior to the rTMS procedure.  The anxiety and “somatization” scores were specifically analyzed to determine whether participants had “anxious depression.”

Results indicated that both depressive and anxious symptoms significantly improved following rTMS.  Those considered to have “anxious depression” experienced substantial improvements in their anxiety and depression symptoms.  While this was a small-scale study, it provides preclinical evidence to suggest that rTMS may provide benefit to those with severe anxiety and depression.

Both depression (total score) and anxiety symptoms improved from pre- to post-treatment with moderate to large treatment effects. Patients with and without anxious depression demonstrated similar rates of improvement in depression. Patients with versus without anxious depression demonstrated larger improvements in anxiety.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23810361

2011: Researchers point out that there haven’t been many trials investigating the potential of rTMS for the treatment of anxiety disorders.  A review of the literature was conducted to determine whether there’s any evidence to suggest rTMS may benefit those with anxiety.  Results from this review suggested that there lacked evidence to suggest therapeutic efficacy of rTMS for the treatment of anxiety disorders.

Authors noted that it was difficult to interpret results due to variations in TMS parameters within the research.  The review explained that sham-controlled trials failed to yield any significant therapeutic effects.  It was suggested that since rTMS stimulates only the outermost 2.5 cm of the cortex, it may fail to benefit those with anxiety due to the fact that they may require deeper cortical penetration.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21631403

2011: Some research has noted that when high-frequency rTMS is administered to the right or left prefrontal corticies among those with panic disorder, anxiety levels increase.  A trial involving 3 individuals with refractory panic disorder experienced slight symptomatic improvement after 10 sessions of rTMS.  A low frequency of 1 Hz delivered to the right prefrontal cortex was the most effective intervention.

When researchers alternated between low frequency to the right PFC and high frequency (20 Hz) to the left PFC, no relief was attained.  Authors noted that administration of a super low frequency (0.3 Hz) to the left and right motor corticies improved symptoms among those with PTSD.  Another study testing 1 Hz rTMS in 9 individuals with PTSD noted reduced hyperarousal and altered levels of hormones / neurotransmitters.

  • Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3271460/

2010: An open-label study involving 14 individuals diagnosed with depression was published in 2010.  This study involved administration of 15 rTMS sessions over a 48 hour period.  Prior to the administration of rTMS, assessments of anxiety, cognitive function, and depression were collected.

The same measures of anxiety, cognition, and depression were again collected immediately post-treatment, after 3 weeks, and again after 6 weeks.  Among those who completed treatment, scores of depression and anxiety were significantly reduced  compared to pre-treatment.  Though this study had a small sample size, results indicated that the procedure improved anxiety (in addition to depression).

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20734360

2009:  A review of the literature was published in 2009 discussing the efficacy of TMS for the treatment of anxiety disorders.  Studies conducted between the dates of 1980 and 2009 were included in the review.  Authors of the review noted that TMS research for anxiety consisted mostly of case studies.

Since no sham-controlled, blinded studies had been published, it is nearly impossible to determine the efficacy of TMS for anxiety.  That said, some case studies suggested that high-frequency stimulation of the right dorsolateral prefrontal cortex ameliorated anxiety among certain individuals with PTSD and panic disorders.  It was noted that anxiety improvements were relatively short-term.

TMS will remain an investigational tool for anxiety until further research is conducted.  Authors expressed that TMS parameters remain unclear for anxiety disorders and considerably more investigation is necessary before its efficacy can be determined.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19455047

2008: A report published in 2008 discussed the usage of TMS for anxiety disorders.  Authors of the report noted that it may provide therapeutic benefit to those with anxiety disorders, including: OCD, PTSD, and panic disorder.  They stated that the cumulative body of scientific research has failed to find TMS more beneficial than sham-TMS (a placebo) for anxiety.

It was also noted that administration of TMS to animals isn’t associated with consistent anxiety reduction.  Authors noted that there is unsubstantial evidence to recommend the usage of TMS for the treatment of anxiety disorders.  However, they do speculate that as we better understand the neural abnormalities among those with anxiety, specific rTMS parameters may provide targeted benefit.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/18928340

2005: A study published in 2005 suggested that rTMS has proven effective for the treatment of depression and anxiety disorder.  Despite the technique’s efficacy for anxiety, researchers document that TMS is also capable of causing anxiety among healthy volunteers (e.g. those without psychiatric abnormalities).  Administration of rTMS to rodent models (rats) also discovered that anxiety increases with rTMS.

Researchers conducted a 10 day trial of rTMS to the brains of rats.  They discovered that anxiety behaviors significantly increased as a result of the stimulation.  However, administration of an anxiolytic medication targeting GABA (Xanax) attenuated symptoms of anxiety induced by rTMS, whereas an SSRI (Paxil) failed to alleviate symptoms.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15905012

2000: A study published in 2000 investigated the antidepressant effect of TMS on 30 individuals with major depression or bipolar depression.  Prior to the administration of TMS, researchers assessed severity of depression based off of the BDI (Beck Depression Inventory) and severity of anxiety with the Hamilton Anxiety Rating Scale.

A total of 20 individuals received TMS across the left prefrontal cortex, while the remaining 10 received a sham-TMS.  Results indicated that 9/20 individuals receiving the TMS experienced significant improvement in depressive and anxiety symptoms, whereas no individuals receiving the sham-TMS improved.  This suggests that TMS may benefit those with depression and anxiety.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/11082469

Research Limitations of TMS for Anxiety Disorders

There are an array of limitations associated with the research of TMS for the treatment of anxiety disorders.  Perhaps the biggest limitation is the fact that there are few (if any) published studies investigating TMS specifically for anxiety.  A large percentage of TMS research is aimed at determining treatment parameters for depression, whereas protocols are still lacking for those with anxiety.

  • Anxiety subtypes: It is important to understand that not all anxiety disorders have the same neurophysiological abnormalities. Someone with social anxiety may have imbalanced activity of brain hemispheres, whereas someone with PTSD may have anxiety as a result of an overactive anterior cingulate cortex.  It will be necessary to investigate how various TMS protocols and parameters impact specific types of anxiety.
  • Deep TMS: A relatively new form of TMS is called “deep TMS” which involves stimulating regions of the brain up to 6 cm.  This differs from traditional rTMS in that rTMS only penetrates the cortex up to 2.5 cm.  Assuming those with anxiety have neurological abnormalities deep within the brain, deep TMS may be the only viable way to correct them.
  • Efficacy unknown: While there is no current evidence to support the recommendation of TMS for anxiety, it cannot be automatically assumed that TMS is ineffective. There are many possible parameters to investigate and it could take years before optimal parameters are determined for anxiety.  Many researchers already have theories regarding specific parameters likely to correct anxiety, but these haven’t been tested.
  • Frequency: The protocols of TMS for the treatment of depression typically involve stimulating the left dorsolateral prefrontal cortex with a high frequency (10 Hz). It is possible that for anxiety, different frequencies than those administered for depression may alleviate symptoms.  It is also necessary to consider that the frequencies of TMS used for depression may exacerbate anxiety.
  • Neuroimaging: It is unclear as to why researchers have yet to use neuroimaging to assess the brain activation among those with certain types of anxiety, and then correct it with targeted TMS. Neuroimaging is beneficial in that it can help researchers determine which regions of the brain are most problematic in anxiety disorders.  The problematic areas can then be targeted with specific TMS frequencies and stimulation protocols.  The use of neuroimaging coupled with TMS may offer personalized treatments for mental illness in the future.
  • Parameters: TMS parameters refer to things like intensity, localization, number of pulsations, gaps between pulsations, and frequencies. In an ideal world, these parameters would be targeted based on an individual’s unique neuroimaging scans, but as of now it is necessary to generalize.  Specific types of anxiety will likely benefit from different parameters than others.  In other words, those with PTSD may derive greater benefit from a completely different set of TMS parameters than individuals with social anxiety.
  • Regional targets: It is important to consider that the regional targeting of TMS in depressive disorders may differ from that necessary to treat anxiety.  Among those with depression, the left dorsolateral PFC is targeted.  It is unclear as to whether individuals with anxiety benefit from prefrontal stimulation; a different region may warrant targeting. Researchers should attempt to fully understand the implications of specific regional targets for those with anxiety.
  • Study blinding: To accurately determine efficacy of TMS for anxiety, researchers should conduct randomized, placebo-controlled studies. Most TMS studies for anxiety have poor designs, aren’t placebo-controlled, and aren’t randomized.  Even among those that are “sham-controlled,” a problem is often that the sham-TMS interventions aren’t convincing enough to be legitimate “shams.”  Due to the lack of robust designs and possibility that the sham-TMS may not be serving as a legitimate “placebo,” the efficacy becomes increasingly difficult to interpret.
  • Sustainability of effect: One (non-placebo controlled) study discovered that TMS stimulation provided benefit to individuals with anxiety. However, this benefit was considered short-term, indicating that the therapeutic effect wasn’t sustainable.  It could be speculated that TMS (especially to regions of the PFC) doesn’t provide long-lasting benefit for those with anxiety.
  • TMS types: The most common type of TMS is called rTMS and stimulates neurons up to 2.5 cm beneath the cortex. This may be beneficial for targeting structures involved in depression, but may not be effective for those with anxiety.  Therefore it may prove superior to consider “deep TMS,” a type of treatment that can penetrate the cortex up to 6 cm, thereby reaching deeper brain structures.  Deep TMS may be the more effective therapy for those with certain types of anxiety.  A combination of both rTMS and deep TMS may also prove effective.

Based on the research, is TMS effective for anxiety disorders?

There is currently inconclusive evidence to determine the efficacy of TMS for the treatment of anxiety disorders.  While many experts speculate that various TMS parameters could benefit individuals with anxiety, these parameters haven’t been fully investigated.  In addition, some studies have suggested that the therapeutic anxiolytic effects derived from TMS are likely to be transient, with anxiety resurfacing quickly post-treatment.

If you have considered TMS for the treatment of anxiety, you may want to reconsider, especially since there are no conclusive parameters (or templates) for practitioners to follow.  There is reason to believe that individuals with depression and comorbid anxiety may derive significant benefit from TMS, especially for the treatment of depression.  Some studies have documented improvements in anxiety and depression among those with “anxious depression.”

Possible Risks of TMS for Anxiety Disorders

Assuming you were to try TMS for the treatment of anxiety disorders, it is important to understand that there are a few risks and/or potential drawbacks.  The biggest risk is that the technique may exacerbate your anxiety.  You also risk wasting money, time, and dealing with treatment-induced side effects.

  • Exacerbation of anxiety: As was mentioned, animal models stimulated with TMS experienced increases in anxiety. Rodent models with normative neurological activity began to exhibit anxious behaviors following the TMS therapy.  Despite the fact that TMS in rodents may differ compared to humans, it is important to consider that the technique could make your anxiety even worse than before – especially with the wrong set of parameters for your specific anxiety.
  • Ineffective: Another reason TMS hasn’t yet been approved by the FDA for the treatment of anxiety is a lack of efficacy. There isn’t any large-scale research to suggest that TMS is effective for anxiety compared to a sham-TMS procedure.  If you were to go through TMS therapy with the hopes of experiencing anxiety reduction, you may find the technique completely ineffective.
  • Side effects: While the TMS side effects are unlikely to be significant, those with anxiety often ruminate on every little sensation and/or experience. Individuals that are hypersensitive and hyperaware of their bodies may find TMS highly unpleasant.  Therefore, there is potential that post-treatment rumination of side effects may ensue, further exacerbating anxiety.
  • Waste of money: For most individuals, the cost of TMS is considered pretty expensive. An average 4 to 6 week TMS protocol costs up to $14,000 – some of which is unlikely to be covered by insurance.  In fact, since the procedure isn’t yet approved for anxiety, none would be covered by insurance.  Therefore you may end up wasting a considerable amount of money (to potentially feel worse) than before.

Possible Benefits of TMS for Anxiety Disorders

It’s only a matter of time before researchers devise a TMS protocol that effectively treats certain types of anxiety.  Eventually, universally designed “TMS” templates may be phased out and specific TMS parameters may be determined based on individual neurochemistry.  In other words, whatever neurological abnormalities are specifically contributing to your (personal) anxiety, the TMS sessions will correct them.

  • Adjunct: There is reason to believe that TMS may serve as an effective adjunct to anxiolytic medications. For example, someone taking a drug like Buspar (for anxiety) may also engage in targeted TMS for 4 to 6 weeks.  The individual may find that the TMS plus pharmaceutical yields synergistic anxiolytic benefit that exceeds each option as standalone treatments.
  • Efficacy: It is highly likely that TMS can treat anxiety, but proper regions of the brain causing anxiety need to get targeted. Targeting the wrong regions could worsen anxiety and/or fail to provide benefit.  As researchers determine the proper regions to target based on hyperactivity and/or hypoactivity – it is very likely that TMS will provide significant benefit.
  • Long-term effects: It is known that benzodiazepines are linked to dementia and permanent memory impairment. Many consider benzodiazepines to be among the most dangerous psychiatric drugs, especially when considering the fact that users rapidly establish tolerance, become dependent, and abrupt discontinuation could be fatal.  While the long-term effects of TMS aren’t well documented, most believe that they are likely to be positive rather than negative.
  • Non-pharmacological: The concept of using TMS for the treatment of anxiety is appealing to many due to the fact that it is non-pharmacological. If it works, people won’t need to take medications every day or worry about potential side effects such as sexual dysfunction and weight gain associated with drugs like SSRIs.  TMS may be a viable “Xanax alternative” without impairing your ability to operate heavy machinery.
  • Personalized: There is potential that TMS could be personalized in the future based on abnormalities within your specific brain. The abnormalities within your brain causing anxiety may be totally different from those in another person’s brain causing anxiety.  The idea of using neuroimaging to devise an individualized treatment protocol is appealing.
  • Sustained effect: While the ability of TMS to produce a sustained effect is unclear, newer evidence suggests that benefits can be maintained for well over a year. By targeting the proper regions of the brain among individuals with anxiety, perhaps the benefits of TMS can be sustained equally as well as they are among those with depression.  When considering that the anxiolytic benefit from TMS may be long-lasting, it could be an ideal treatment for anxiety.
  • Templates: An effective set of parameters (or template) when using TMS for depression is high-frequency (10 Hz) stimulation of the left dorsolateral prefrontal cortex. It is hoped that researchers will focus on devising a specific effective template for the treatment of anxiety disorders.  After an initial effective template, they may focus on developing other specific templates based on specific anxiety subtypes such as: panic disorder, generalized anxiety, social anxiety, etc.

Further research of TMS for anxiety is warranted

Currently the biggest concern for those considering TMS as an intervention for anxiety is the lack of research.  There are very few studies that have been published that investigate the efficacy of TMS for anxiety.  Therefore, any investigations and new trials of TMS for the treatment of anxiety would be helpful.

Researchers need to first determine an optimal set of parameters for the treatment of anxiety.  Initial research of TMS for anxiety could be conducted in small-scale pilot studies.  Once an effective set of parameters is discovered, trials can be conducted with placebo-controlled, randomized designs to test efficacy in a larger population.

It may be beneficial to first investigate the usage of TMS for the most common types of anxiety such as generalized anxiety disorder (GAD) before other subtypes are considered.  Various types of TMS (rTMS and deep TMS) should be investigated to understand what methods produce the best outcomes. The small amount of available research of TMS for anxiety has suggested several protocols that may mitigate anxious symptoms.

Some evidence suggests that low frequency stimulation of the right prefrontal cortex at 1 Hz is likely to improve symptoms of anxiety. This is based on the theory that hyperactivity in the right prefrontal cortex can contribute to anxiety.  Other potentially beneficial protocols involve usage of extremely low frequencies (i.e. 0.3 Hz) delivered to the left and right motor corticies.

Authors of one study highlight the possibility of targeting the right medial prefrontal cortex with a low frequency and the left medial prefrontal cortex with a higher frequency.  They believe that this type of protocol could promote hemispheric balance among those suffering from anxiety as a result of overactivity in one hemisphere.

Have you tried TMS (for depression) and noticed that it helped your anxiety?

Many people with depression have comorbid anxiety disorders.  The comorbid anxiety may exacerbate depressive symptoms and make it tough to treat the combined conditions with pharmaceutical drugs.  Those that are unable to get relief from depressive symptoms with medications may end up trying TMS.

Assuming you’ve tried TMS for depression, mention whether you noticed a simultaneous improvement in symptoms of anxiety.  Discuss the severity of your anxiety prior to TMS therapy, and contrast your pre-TMS anxiety with how you’re feeling now.  Was there significant improvement in anxious symptoms and thinking following the TMS protocol?

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