SWISS MEDICAL EXPERTISE: MALLORCA, ZURICH, LONDON, OFFSHORE

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Transcranial magnetic stimulation (TMS) therapy is a potential therapeutic tool in several psychiatric and neurological diseases including but not limited to Depression, Anxiety, Panic Disorder, Spinocerebellar degeneration, movement disorders, urinary incontinence, chronic tinnitus, migraine, chronic pain, and smoking cessation. Numerous reports have showed the beneficial effects of TMS as a treatment of Major Depressive Disorder and Parkinson disease, while others found no substantial effects. To date, it is not yet fully agreed upon by medical authorities whether TMS has a therapeutic effect in managing diseases other than psychiatric illnesses.

The major dispute result from the difference in the evaluation methods of the effects and stimulation parameters in those studies. With the hope that it will go forth into new treatments for psychiatric and neurological disorders, physical rehabilitation and pain management with much less side effects, TMS therapy is being studied comprehensively across various disorders and even several disciplines. There are currently large clinical trials looking at the effectiveness of TMS in conditions such as obsessive compulsive disorder, pediatric depression, nicotine addiction, post-traumatic stress disorder and bipolar disorder. While these are promising prospects for research, the fact of the matter is that use of TMS for these conditions has been considered “off-label” and anecdotal for many years.

Anxiety is thought to be the outcome of a misfiring of electrochemical neurological signals due to both hypoactive and hyperactive areas of the brain, generating a feeling of excessive fear or distress, leading to physical symptoms including shortness of breath, racing heart, muscle spasms, and Gastrointestinal upset. After hundreds of small studies performed around the globe with very positive results, there is no more assurance that TMS can be a highly effective treatment for various anxiety disorders, including generalized anxiety disorder (GAD), panic disorder, and obsessive-compulsive disorder.

Nearly half of those in the United States who are diagnosed with depression are also diagnosed with some sort of anxiety disorder and vice versa. Due to this, the promising results from the use of TMS for depression points to positive outcomes for using TMS as a treatment for anxiety as well. As a highly effective treatment for depression, symptoms of anxiety will often improve during the cycles of TMS treatment. Though the use of TMS therapy is not as well established as it is for the treatment of depressive illnesses, it is pertinent to say that it will also help individuals with anxiety even without marked comorbidity with depression.

What Conditions can be Treated by NeuroFeedback?

A small number of studies have suggested that TMS treatment may benefit patients with Generalized Anxiety Disorder. The mechanism of action for this is reducing the neuronal function in the overactive areas of the brain centers linked with mood and emotional balance. TMS can be applied to the right side of the brain that is hyperactive in anxiety. There is often increased neuron cell bodies stimulation in the prefrontal cortex. TMS may reduce the activity in this region, according to a study conducted in 2019.

The US Food and Drug Administration (FDA) has expanded indication for the noninvasive Brainsway Deep Transcranial Magnetic Stimulation (Deep TMS) System to include treatment of comorbid anxiety symptoms in adult patients with depression, the company has announced. As reported by Medscape Medical Newsthis neurostimulation deep TMS system has previously received FDA approval for treatment-resistant major depression, obsessive-compulsive disorder, and smoking addiction. In the recent announcement, Brainsway reported that it has also received 510(k) clearance from the FDA to market its TMS system for the reduction of anxio-depression symptoms.

Obsessive compulsive disorder (OCD) is a chronic, debilitating, often severe neuropsychiatric disorder leading to a colossal impairment in occupational interpersonal functions. Research data suggests that one in ten patients remain treatment-refractory and resistant to medication despite multiple courses of treatment. For these severe, treatment resistant patients, TMS therapy can be of high value as a treatment option, either alone or in combination with medication as it has been found to reduce medication resistance.

OCD Treatment and Therapies

As with the role of TMS therapy in anxiety, randomized and placebo controlled trials (RCTs) of Transcranial magnetic stimulation (TMS) in the treatment of obsessive compulsive disorder (OCD) have yielded conflicting results, which may be due to the variability in TMS parameters used. That being said, a recent meta-analysis (published in 2018) on the effectiveness of TMS therapy in treating OCD provided the much needed substantial results. In this study, the scientists performed a random-effects meta-analysis with the outcome measure as pre and post changes in Yale Brown Obsessive Compulsive Scale (YBOCS) scores.

Subgroup analyses suggested that low frequency TMS was more effective in achieving response and remission for OCD patients than high frequency TMS. The effectiveness of TMS was also greater at 12 weeks follow-up than at four weeks follow-up. This meta-analysis also implies that low frequency TMS applied over the supplementary motor area may offer the greatest effectiveness in the treatment of OCD. The therapeutic effects of TMS also appear to persist post treatment and may offer beneficial long term effectiveness. Three anatomical regions of brain have been identified for application of TMS therapy of which the supplementary motor area in particular and the orbitofrontal cortex seem to be the most promising in terms of potential efficacy in patients of OCD. In 2018, the US Food and Drug Administration (FDA) approved TMS therapy for treatment OCD. Since then, TMS therapy has been widely used for OCD, particularly for medication resistant OCD.

TMS therapy was approved by FDA in 2008 for Major Depressive Disorder (MDD). Since then, it has been a mainstay treatment modality for patients with depression when at least one category of anti-depressant medication has been unsuccessful to achieve a significant response. A multicenter, double-blind TMS study demonstrated that ~30% of individuals in the study’s treatment group accomplished significant remission after five weeks of TMS therapy. The study was performed with a total of 233 patients diagnosed with Major Depressive Disorder and those who had already failed to respond to anti-depression medications or could not withstand the present therapeutic treatments because of adverse reactions of drugs. The TMS device used in the study was granted FDA approval for the treatment of depression in 2013. The FDA cleared a much more sophisticated TMS device in 2017 for individuals with resistant depression. At the time, this innovative system is the only FDA approved TMS treatment that can be provided in a short span of 19 minutes. The duration of treatment may vary as per physician or practitioner’s  advice and depending on the diagnosis. 

Depression Luxury Treatment and Therapies

Speaking of the effectiveness and long-term remission of symptoms of depression, most patients who complete a full cycle of treatment would experience improvement in their symptoms for six months to a year or even more. One study conducted in 2013 examined 12 month outcomes for patients who completed TMS depression therapy. The study concluded that after a year, 45% were in complete remission and 68% had improved symptoms. These statistics are welcoming and offer a tremendous hope for people who suffer from depressive illness and have been unable to find a significant relief through psychotherapy and medication alone. In some cases, TMS has proven to be most effective when used in combination with antidepressant medication. 

In 2018, the FDA approved a newer and faster treatment protocol for a TMS device first approved in 2015. At that time, each treatment session with this device lasted  approximately 37 minutes, with about 25 to 30 total sessions required. With the new treatment protocol which would utilize the intermittent theta burst stimulation, a treatment session could be as short as 3 minutes. In time, various comprehensive experimental studies have been conducted which further strengthens the role of TMS therapy in the management of depression.

Post-traumatic stress disorder (PTSD) is an anxiety disorder caused by witnessing or being involved in extremely frightening or distressing events. When PTSD symptoms are uncontrollable and intense, they can interfere with your work, day-to-day functioning and relationships. Various brain centers and their functions are affected in those who suffer from PTSD. Likewise, similar structural and functional changes can occur in brain in individuals who have been exposed to long term trauma. Key regions of the brain that can have a structural or functional following in trauma include, but not limited to:

  1. The amygdala: This is a small almond shaped structure that deals with survival instincts and the way you express different emotions, especially fear.
  2. The ventromedial prefrontal cortex (vmFC): This is a more sophisticated region of the brain that also processes emotions
  3. The hippocampus: Hippocampus is associated with for storing and retrieving memories.

Radiological studies of the brain show that PTSD patients have diminished activity of the brian in the vmPFC with an overactive amygdala. In medical conditions where vmPFC loses regulatory control of amygdala will lead to anxiety disorders. The hippocampal centers which helps to distinguish between the present and the past also shrinks. This implies that PTSD patients would find it difficult to differentiate between the past trauma and the present situation.

TMS therapy functions by eliciting the cells in the vmPFC with electromagnetic impulses delivered by an electromagnetic coil. This treatment also helps to regulate cells in the other brain regions linked with trauma and PTSD, possibly returning back to normal levels of activity and restoring balance and stability in brain to help improve the symptoms of trauma and PTSD. Research demonstrates that TMS therapy is an effective PTSD treatment. Similar to other psychiatric illnesses, TMS therapy is reserved for treatment resistant patients of PTSD. TMS therapy may not completely cure PTSD but it can help reduce symptoms and make them more manageable. In this way, TMS therapy for PTSD can bring back order in daily life without the side effects of psychiatric medication

Existing treatments for chronic pain are frequently ineffective, or their efficacy is restricted by adverse effects. TMS has progressed as a new method in this therapeutic domain. However, the exact mechanisms involved to bring about the analgesic effect of TMS is unknown and the ideal parameters of TMS for chronic pain relief are yet to be established. When other treatment methods fail, the rationale for the use of TMS for chronic pain .

TMS therapy for chronic pain, on average,  uses 900-1200 pulses at 1 Hz bursts of electromagnetic pulses that can take approximately 15-20 minutes. Keep in mind that these numbers can vary from patient to patient and the approach can be different according to patient’s EEG evaluation. TMS excites highly specific regions of the brain known to control the pain response. TMS therapy creates physiological  and structural changes in the brain itself.

Although TMS therapy is presently FDA approved for treatment of severe depressive disorders and suicidal thoughts, scientific evidence also indicates that TMS is a highly effective treatment for individuals who require relief from chronic pain. That being said, TMS therapy for chronic pain is deemed “off-label,” and the FDA is yet to approve TMS for treatment of chronic pain. Nevertheless, there is a strong foundation in the shape of consistent clinical trials that will lead FDA approval in the near future.

As a consequence of latest studies conducted at Stanford University, individuals enduring chronic pain were able to get respite from the symptoms after a cycle of TMS therapy. Such outcomes were also reported in patients suffering a painful musculoskeletal condition characterized by long term fatigue and pain without an obvious cause and in patients of fibromyalgia. A meta-analysis of 9 trials conducted in the US in 2017 concluded that TMS improves the effectiveness of medication treatment in chronic pain patients. It also states that TMS is not linked with any direct side effects. However, the frequency and of TMS is currently highly variable and needs to be standardized.

Cigarette smoking is one of the major source of nicotine addiction worldwide. About 75-80% of consistent smokers meet the ICD-10 criteria of dependence. Smoking is one of the leading cause of morbidity and mortality across the Europe and US. It has been found to harm nearly every organ system in the body and is the leading cause of preventable death worldwide In Germany, for instance, approximately 120,000 deaths per annum are caused by tobacco-associated ailments. Transcranial Magnetic Stimulation works by targeting the areas of the brain that control addiction. With no anesthetic, no medication, no need for hospitalization and no recovery time, this non-invasive treatment uses a repetitive magnetic pulse to stimulate the parts of the brain that cause alcohol cravings and dependence. In contrast, therapeutic interventions such as or bupropione or nicotine substitution, yield poor abstinence rates at their best, of 30% after 12 months according to one study.  

In August 2020, FDA cleared BrainsWay deep TMS treatment for nicotine addiction after the compelling data from their large, randomized pivotal study of 262 subjects. When the subjects were evaluated after 4 weeks of treatment with diary records and confirmatory urine samples, the Continuous Quit Rate (CQR) at 4 weeks was ~28% in the active Deep TMS group compared to ~12% in the placebo group. On the basis of primary efficiency data from this study, BrainsWay Deep TMS system showed a positive result of treatment and revealed a favorable effect in cessation of smoking.

A significant secondary efficiency analysis was the average cigarettes smoked per day (CPD). The variance in the mean of CPD per subject from start point to the end of the period of study (6 weeks follow up for smokers and 4 months for quitters) was statistically significant and notably lesser in the Deep TMS group in comparison with the placebo group. There were no reports of seizures in the study and as expected, the most frequent side effect was headache. The reports of headache were not statistically different between the procedure group and the placebo group. Some of the minor side effects that were reported more often included back pain, muscle twitching, application site discomfort, and procedural anxiety.

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