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Antidepressants have revolutionized depression treatment. But these medications are only effective for some. Are there alternative treatments for patients who don’t respond to antidepressants?

Antidepressants were first prescribed in the 1950s and have completely changed the way healthcare providers treat depression. (1) Antidepressants have helped catapult scientists’ understanding of the mechanisms that cause depressive symptoms and have provided symptom relief to millions of people worldwide.

But what if you’re one of the millions of people who have not seen improvement while taking antidepressants? Today, scientists and doctors alike recognize that a significant number of people are not responding to antidepressants.

Antidepressants Relieve Symptoms, But Not for Everyone

Antidepressants are considered the first line of treatment for depression. This is because they have been proven to relieve depressive symptoms, especially for individuals with severe depression. (2) However, sometimes, the first antidepressant will not relieve symptoms of depression. For this reason, physicians recommend trying different antidepressants.

There are multiple types of antidepressants. Each one works by using different mechanisms to relieve depressive symptoms. For example, selective serotonin reuptake inhibitors (SSRIs) work by increasing levels of serotonin (a neurotransmitter that regulates mood and behavior) in the brain. Tricyclic antidepressants work by increasing levels of both serotonin and norepinephrine (a neurotransmitter and hormone known to affect mood) in the brain. (3, 4)

According to a study published in The Journal of the American Medical Association, of the more than 9,000 individuals who filled out a questionnaire and were diagnosed with major depressive disorder (MDD), 51 percent of them received treatment. Of the people who received treatment, treatment was only sufficient for approximately 40 percent. This study suggests that standard treatments for depression are not adequate and that many patients diagnosed with depression need alternative treatment options. (5)

If you’ve tried two or more antidepressants, while simultaneously seeing a talk therapist, and have not noticed an improvement in your symptoms, you may have treatment-resistant depression. In fact, roughly one-third of patients diagnosed with Major Depressive Disorder (MDD) are said to have treatment-resistant depression. (6)

Why Don’t Antidepressants Work for Everyone?

The exact cause of treatment-resistant depression is unknown. However, scientists have recently uncovered a possible contributing factor: metabolic disorders.

A study published in The American Journal of Psychiatry evaluated levels of certain metabolites (substances formed during the process of metabolism) in 33 adolescents and young adults with documented treatment-resistant depression. Metabolites were measured from samples of urine, blood plasma, and cerebrospinal fluid (CSF).

Scientists discovered that 21 of the 33 subjects had abnormalities in the levels of certain metabolites in CSF samples. The results of this study suggest that metabolic imbalances might contribute to treatment-resistant depression. (7)

TMS: A Novel Depression Treatment

TMS was approved by the FDA in 2008 specifically for individuals who do not respond to antidepressants and have treatment-resistant depression. (8) A review of 18 studies published in 2014 in The Journal of Clinical Psychiatry clearly demonstrated the efficacy of TMS treatment compared to sham or placebo treatment in individuals with treatment-resistant depression. (9)

Furthermore, a study published in The Journal of Clinical Psychiatry showed that one course of TMS is effective enough to produce long-lasting effects. In fact, among patients who met response or remission criteria, 62.5% continued to show improvement one year following treatment. (10)

How Does TMS Therapy Relieve Symptoms of Depression?

TMS does not require anesthesia of any kind and is performed as an outpatient procedure. That means that patients can return to work immediately following their appointment.

During a TMS session, the patient sits comfortably in a reclined chair. The doctor then positions a magnetic coil close to a predetermined location of the patient’s scalp. This magnetic coil gives off magnetic pulses that generate an electric current in the brain.

This electric current stimulates neuron (brain cell) activity in specific areas of the brain known to be associated with depression. By activating these areas, doctors hope to stimulate neurons so they release more neurotransmitters (a chemical released by neurons that allow them to communicate with one another) and restore normal communication along neuron pathways that travel to other regions of the brain. (11)

A course of TMS treatment requires five TMS sessions per week over the course of six weeks. It is followed by a three-week tapering-off period where the patient attends gradually fewer sessions each week.

TMS Therapy as an Augmented Treatment With Antidepressant Medications

Sometimes, patients taking antidepressants notice improvement of depressive symptoms initially but then stop seeing results. Scientists have explored the use of TMS therapy in conjunction with antidepressants and have recorded the outcomes. Their studies have shown that TMS can increase the effects of certain antidepressants.

A study published in Biological Psychiatry observed the effects of TMS therapy when applied to patients taking amitriptyline (a tricyclic antidepressant). In this study, 46 individuals diagnosed with depression were given TMS therapy over the course of four weeks (one session a day for five days a week) while simultaneously taking amitriptyline.

Participants were randomly chosen to receive either sham (placebo) TMS treatment or active TMS treatment. Results clearly demonstrated a significant reduction in scores on multiple depression rating scales with active TMS compared to sham TMS. There were no adverse effects. These results suggest that TMS therapy augments the effects of amitriptyline and may do so for other antidepressants. (12)

Although TMS has been shown to augment the effects of some antidepressants, it may increase the risk of certain side effects when taken with certain other antidepressants. For patients currently taking an antidepressant, it’s important to speak with your doctor as to whether TMS is a safe treatment option according to your current treatment plan.

Does TMS Have Any Side Effects?

TMS is associated with few side effects. Those that have been observed in clinical trials are rare and/or mild. Side effects of TMS include scalp discomfort, mild headache, and tingling or twitching of the facial muscles. (13) The most severe side effect associated with TMS is the risk of seizure. This risk is less than one percent in nonepileptic individuals. (14)

If you’re currently working with a psychologist or psychiatrist, ask your doctor whether TMS therapy may be right for you.

Additional Content by Author:  Pros & Cons of Common Depression Treatments

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References:
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  1. López-Muñoz, Alamo C. Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today. Current Pharmaceutical Design. 2009;15(14):1563-86. Click Here. Accessed June 11, 2019.
  2. Depression: How effective are antidepressants? InformedHealth.org — Institute for Quality and Efficiency in Health Care (IQWiG). Published January 28, 2015. Updated January 12, 2017. Click Here. Accessed June 11, 2019.
  3. Selective serotonin reuptake inhibitors (SSRIs). The Mayo Clinic. Updated May 17, 2018. Click Here. Accessed June 11, 2019.
  4. Tricyclic antidepressants and tetracyclic antidepressants. The Mayo Clinic. Updated June 28, 2016. Click Here. Accessed June 11, 2019.
  5. Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, and Wang PS. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). The Journal of the American Medical Association. 2003; 289(23): 3095-105. Click Here. Accessed June 11, 2019.
  6. Ionescu DF, Rosenbaum JF, and Alpert JE. Pharmacological approaches to the challenge of treatment-resistant depression. Dialogues in Clinical Neuroscience. 2015; 17(2): 111–126. Click Here. Accessed June 11, 2019.
  7. Pan LA, Martin P, Zimmer T, Segreti AM, Kassiff S, McKain BW, Baca CA, Rengasamy M, Hyland K, Walano N, Steinfeld R, Hughes M, Dobrowolski SK, Pasquino M, Diler R, Perel J, Finegold DN, Peters DG, Naviaux RK, Brent DA, Vockley J. Neurometabolic Disorders: Potentially Treatable Abnormalities in Patients With Treatment-Refractory Depression and Suicidal Behavior. The American Journal of Psychiatry. 2017; 174: 42–50. Click Here. Accessed June 11, 2019.
  8. Horvath JC, Mathews J, Demitrack MA, and Pascual-Leone A. The NeuroStar TMS device: conducting the FDA approved protocol for treatment of depression. Journal of Visualized Experiments. 2010;(45). pii: 2345. Click Here. Accessed June 11, 2019.
  9. Gaynes BN, Lloyd SW, Lux L, Gartlehner G, Hansen RA, Brode S, Jonas DE, Swinson Evans T, Viswanathan M, and Lohr KN. Repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and meta-analysis. The Journal of Clinical Psychiatry. 2014;75(5):477-89. Click Here. Accessed June 11, 2019.
  10. Dunner DL, Aaronson ST, Sackeim HA, et al. A multisite, naturalistic, observational study of transcranial magnetic stimulation for patients with pharmacoresistant major depressive disorder: Durability of benefit over a 1-year follow-up period. J Clin Psychiatry. 2014;75(12):1394-401. Click Here. Accessed August 17, 2018.
  11. Neurostar mechanism of action. YouTube: Neurostar Advanced Therapy. Click Here. Published on Nov 29, 2016. Accessed on June 11, 2019.
  12. Rumi DO, Gattaz WF, Rigonatti SP, Rosa MA, Fregni F, Rosa MO, Mansur C, Myczkowski ML, Moreno RA, Marcolin MA. Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: a double-blind placebo-controlled study. Biol Psychiatry. 2005 Jan 15;57(2):162-6. Click Here. Accessed June 11, 2019.
  13. Transcranial magnetic stimulation. The Mayo Clinic. Updated Nov. 27, 2018. Click Here. Accessed June 11, 2019.
  14. Rossi S, Hallett M, Rossini PM, Pascual-Leone A, and The Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clinical Neurophysiology. 2009; 120(12): 2008–2039. Click Here. Accessed June 11, 2019.

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Financial disclosure: Dr. Woo is one of the few providers offering TMS in NYC’s Midtown Manhattan area. His business could, therefore, benefit from this article. TDWI did not receive any compensation for publishing this article. Rather, we published it because of the quality of its content.

David Woo, MD
David Woo, MD is certified in Psychiatry and Geriatric Psychiatry by the American Board of Psychiatry and Neurology. He has been seeing patients in private practice since 2002, always with the goals of combining evidence-based medicine with psychodynamic psychotherapy and collaborating with other mental health professionals to ensure the best possible outcomes for his patients. He is one of the few providers offering TMS in NYC’s Midtown Manhattan area. TMS is a noninvasive, drug-free treatment option for treatment-resistant depression. He performs this treatment at his practice in Midtown Manhattan, New York City. He is one of a number of providers who offer this treatment in Midtown. He has been in private practice since 2002, and has been performing TMS in New York since 2017. His greatest clinical interests include helping patients suffering from depression, anxiety, and obsessive-compulsive disorder.

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