Why Transcranial Magnetic Stimulation (TMS) Therapy May Work Better Than Trying Another Antidepressant

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Approximately one-third of patients with depression don’t find relief with antidepressants. TMS is an alternative treatment option that is proven to reduce and eliminate depressive symptoms, even when antidepressants don’t. 

Transcranial magnetic stimulation, also called TMS or rTMS, is a relatively new alternative depression treatment option. Physicians and researchers know that antidepressants work better for some patients than others. When patients don’t respond to antidepressants, they are said to have treatment-resistant depression. Antidepressants have helped millions of people with depression, but many patients with treatment-resistant depression need the option of alternative treatment in order to find relief from depressive symptoms.

TMS is FDA-approved and clinically proven to relieve depressive symptoms in patients diagnosed with major depressive disorder (MDD) and multiple studies show that it is safe and effective in patients with treatment-resistant depression. (1,2,3,4)

Examining Two Major Studies Illuminates the Efficacy of TMS vs Antidepressants for Patients With Treatment-Resistant Depression  

A comparison of the results from two landmark studies, the STAR*D study and the Carpenter study, shows that patients with treatment-resistant depression are more likely to find relief from depressive symptoms with TMS compared to trying another antidepressant.

The STAR*D Study

The goal of the STAR*D study was to understand how effective antidepressants are in completely relieving depressive symptoms (achieving remission). To accomplish this, researchers enrolled more than 4,000 patients across the US between the ages of 18 and 75 who had been diagnosed with major depressive disorder (MDD). Patients followed a four-step treatment protocol developed by the researchers:

Level 1—Remission rate 33%: All patients were treated with Citalopram (an SSRI antidepressant). 

Level 2—Remission rate 25%: Patients who did not achieve remission with Citalopram could choose their level 2 treatment: a) continue treatment with Citalopram and augment treatment with cognitive-behavioral therapy or with a different random medication (Bupropion sustained-release or Buspirone), or b) stop taking Citalopram and continue treatment with a different random medication (Bupropion sustained-release, Venlafaxine extended-release, or Sertraline).

Level 3—Remission rate 13-20%: Patients who did not achieve remission after level 2 treatment could choose their level 3 treatment: a) continue their current treatment and augment treatment with a different random medication (Lithium or T3 thyroid hormone), or b) stop their current treatment and receive a different random medication (Mirtazapine or Nortriptyline).  

Level 4—Remission rate 7-14%: All patients who did not achieve remission after level 3 treatment ceased their current treatment and were randomly assigned a different medication (Tranylcypromine or Mirtazapine plus venlafaxine extended-release). 

Patients spent 14 weeks at each treatment level, taking the maximum tolerated dose. Once a patient had reached remission, they continued with their current treatment and were followed for up to one year. This study shows that at tier-3 and tier-4 levels of treatment (after trying two or more different antidepressant medications, the probability of achieving remission significantly decreases. (5)

The Carpenter Study

The goal of the Carpenter study was to evaluate the efficacy of TMS therapy for patients who have been diagnosed with treatment-resistant depression. Study participants included 307 adult patients diagnosed with major depressive disorder (MDD) who had tried an average of 2.5 antidepressants without satisfactory improvement of depressive symptoms. All patients were treated with TMS in clinics across the US for six weeks. At the end of six weeks, the clinician-reported remission rate was 37.1%. Patient-reported remission ranged from 26.5% to 28.7% and up to 56.4% of patients reported an improvement in depressive symptoms. (2)

Comparing the Results

During the STAR*D study, the remission rate associated with antidepressants significantly decreased to 13-20% and 7-14% when a third and fourth antidepressant were tried, respectively. During the Carpenter study, patients had tried an average of 2.5 antidepressants and achieved a patient-reported remission rate as high as 28.7% and a clinician-reported remission rate of 37.1%. A comparison of these results clearly shows that after 2 antidepressants, patients are more likely to find relief of depressive symptoms with transcranial magnetic stimulation than with a different antidepressant. 

TMS Treatment Uses Magnetic Pulses to Relieve Depressive Symptoms

TMS is a medication-free depression treatment that uses magnetic pulses to stimulate neurons (brain cells) in brain regions associated with depression, more specifically the left dorsolateral prefrontal cortex (DLPFC). TMS is administered as an out-patient procedure that does not require surgery, sedation, or anesthesia. Since TMS therapy involves administering repetitive magnetic pulses, it’s often referred to as repetitive TMS or rTMS.

During a TMS treatment session, patients sit comfortably in a reclined chair and a magnetic coil is carefully placed over the scalp. The magnetic coil painlessly administers repetitive magnetic pulses that create an electrical response in the brain. This electrical response stimulates neurons that are thought to be underactive and prompts them to release more neurotransmitters (chemicals that facilitate communication between neurons). (6)

After a TMS session, neurons enter into a state of rearranging or reorganization, which allows for the development of new neuron pathways. The brain functions through neural networks that communicate with neurons in other brain regions as well as with cells throughout the body. The brain can form new pathways based on our behaviors, habits, and thoughts. (7,8) Research shows that not only are neurons capable of “reorganizing” after a TMS session, but they show a preference for these new pathways, even hours after a TMS session. (9,10)

TMS has also been shown to increase blood flow and oxygen to underactive areas of the brain.(11) Early studies report that patients with depression have less blood flow and volume in certain regions of the brain. (12)

TMS Can Be Used as an Augmentative Therapy With Certain Antidepressants

In some cases, TMS may be used in conjunction with an antidepressant as an augmentative therapy. An analysis of several random clinical trials shows that TMS increases the effects of certain antidepressants in patients diagnosed with treatment-resistant depression. (13)

TMS may be used as an augmentative treatment when patients experience antidepressant treatment (ADT) tachyphylaxis or “breakthrough” depression. This occurs when patients initially find relief of depressive symptoms with antidepressants, but eventually stop seeing results. Additionally, sometimes patients can feel anxious about leaving their antidepressant during TMS treatment, even if it’s not working or if it has stopped working.

Patients can take an antidepressant simultaneously (during TMS treatment) or in combination with TMS treatment (patients take the antidepressant before and after TMS treatment, but not during the treatment course). 

Insurance Coverage for rTMS Treatment in New York City

Most major insurance companies and Medicare cover the costs of TMS therapy–NYC residents with insurance coverage can get TMS either partially or fully covered. To find out whether your insurance plan covers the cost of TMS, call your insurance provider. 

If you’re interested in learning more about TMS therapy, NYC is home to a number of psychiatrists who offer this treatment option. If you’re currently working with a psychologist or a psychiatrist, ask your doctor if TMS therapy may be right for you. 

Resources:

  1. McClintock SM, Reti IM, Carpenter LL, et al. Consensus Recommendations for the Clinical Application of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Depression. J Clin Psychiatry. 2018;79(1):16cs10905. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846193/. Accessed November 10, 2020.
  2. Carpenter LL, Janicak PG, Aaronson ST, et al. Transcranial magnetic stimulation (TMS) for major depression: A multisite, naturalistic, observational study of acute treatment outcomes in clinical practice. Depression and Anxiety. 2012;29(7):587-96. https://pubmed.ncbi.nlm.nih.gov/22689344/. Accessed November 10, 2020.
  3. Somani A, Kar SK. Efficacy of repetitive transcranial magnetic stimulation in treatment-resistant depression: the evidence thus far. Gen Psychiatr. 2019;32(4):e100074. Published 2019 Aug 12. doi:10.1136/gpsych-2019-100074. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738665/. Accessed November 10, 2020.
  4. Lee JC, Blumberger DM, Fitzgerald PB, Daskalakis ZJ, Levinson AJ.The role of transcranial magnetic stimulation in treatment-resistant depression: a review. Curr Pharm Des. 2012;18(36):5846-52. https://pubmed.ncbi.nlm.nih.gov/22681165/. Accessed November 10, 2020.
  5. Gaynes BM, Rush AJ, Madhukar HT, Wisniewski SR, Spencer D, Maurizio F. The STAR*D study: Treating depression in the real world. Cleveland Clinic Journal of Medicine. Jan 2008;75(1):57-66. https://pubmed.ncbi.nlm.nih.gov/18236731/. Accessed November 10, 2020.
  6. Neurostar mechanism of action. YouTube: Neurostar Advanced Therapy. https://www.youtube.com/watch?v=r4WISNwv3nc. Published on Nov 29, 2016. Accessed on November 10, 2020.
  7. University of California – San Diego. (2016, May 26). How the brain makes, and breaks, a habit: Neuroscience study identifies brain chemicals, neural pathway involved in switching between habitual behavior, deliberate decision-making. ScienceDaily. www.sciencedaily.com/releases/2016/05/160526185419.htm. Accessed November 12, 2020.
  8. Christina M. Gremel et al. Endocannabinoid Modulation of Orbitostriatal Circuits Gates Habit Formation. Neuron. 2016;90(6):1312-1324. https://pubmed.ncbi.nlm.nih.gov/27238866/. Accessed Novebmer 12, 2020.
  9. Kozyrev V, Staadt R, Eysel UT, and Jancke D. TMS-induced neuronal plasticity enables targeted remodeling of visual cortical maps. Proceedings of the National Academy of Sciences. 2018;115(25):6476-6481. https://www.pnas.org/content/115/25/6476. Accessed November 11, 2020.
  10. Ruhr-University Bochum. What effect does transcranial magnetic stimulation have on the brain? Published June 5, 2018. https://www.sciencedaily.com/releases/2018/06/180605103511.htm. Accessed November 11, 2020.
  11. Mesquita RC, Faseyitan OK, Turkeltaub PE, et al. Blood flow and oxygenation changes due to low-frequency repetitive transcranial magnetic stimulation of the cerebral cortex. J Biomed Opt. 2013;18(6):067006. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678989/. Accessed November 11, 2020.
  12. Bench CJ, Friston KJ, Brown RG, Scott LC, Frackowiak RS, Dolan RJ. The anatomy of melancholia–focal abnormalities of cerebral blood flow in major depression. Psychol Med. 1992;22(3):607-615. https://pubmed.ncbi.nlm.nih.gov/1410086/. Accessed November 11, 2020.
  13. L Bangshan, Zhang Y, Zhang L, and Li L. Repetitive transcranial magnetic stimulation as an augmentative strategy for treatment-resistant depression, a meta-analysis of randomized, double-blind and sham-controlled study. BMC Psychiatry. 2014; 14: 342. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264336/. Accessed November 11, 2020.

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