TMS is the Next New Thing in the Treatment of Depression

​Major depressive disorder (MDD) is one of the most common psychiatric disorders, affecting more than 264 million people worldwide, plus the global prevalence of MDD increased by almost 13% during 2007–2017. In addition, MDD is the most common mood disorder in the United States, with devastating social, economic, and personal consequences.  However, there is a new treatment in town that offers promise to help treat this awful scourge.

Transcranial Magnetic Stimulation is Industrial Medicine's Next New Thing to Treat MDD

Although MDD may occur only once, people typically have multiple episodes. Symptoms include:

• Feelings of sadness, tearfulness, emptiness, or hopelessness.
• Angry outbursts, irritability or frustration, even over small matters.
• Loss of interest or pleasure in most or all normal activities, such as sex, hobbies, or sports.
• Sleep disturbances, including insomnia or sleeping too much.
• Tiredness and lack of energy, so even small tasks take extra effort.
• Reduced appetite and weight loss or increased cravings for food and weight gain.
• Anxiety, agitation, or restlessness.
• Slowed thinking, speaking, or body movements.
• Feelings of worthlessness or guilt, fixating on past failures or self-blame.
• Trouble thinking, concentrating, making decisions, and remembering things.
• Frequent or recurrent thoughts of death, suicidal thoughts, suicide attempts, and suicide.
• Unexplained physical problems, such as back pain or headaches.

 
There’s nothing new about MDD.  The first references to depression appeared in ancient Mesopotamian texts about four thousand years ago.   Historically orthodox religious authorities used witchcraft to treat afflicted people, and some would argue that science is rebranded witchcraft for the treatment of MDD, with some justification.

Fascinating facts about MDD in the United States:

• MDD is most prevalent in adults, with a median age of onset in the 20s.
• Adults are twice as likely to have MDD than adolescents or older adults.
• Females are two-to-three times more likely to have MDD than their male counterparts, regardless of age group.
• Between about one-third and one-half of MDD patients have treatment-resistant depression.
• Even patients who respond to currently available antidepressant drugs must wait at least four and as many as 12 weeks before they recover.
• About 37% of individuals suffering from MDD are either unemployed or out of the labor force.
• Only about 60% of the MDD population in the workforce is receiving medical treatment for MDD.
• In 2000, the total economic impact of MDD was about $83 billion.
• Workplace-related costs (missed work days, reduced productivity, and health care expenses) were about $52 billion.
• Employees with MDD cost their employers approximately double in health care expenses, are more likely to file for disability and be unemployed, and missed about 14 hours per month than ‘healthy’ individuals.

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Traditional psychiatry and psychology relied initially upon standard psychotherapeutic models, including a variety of approaches, and these were effective in mild cases.  Severe cases of depression, however, proved resistant to talk therapy, and of course, with the advent of technology came experimentation with a variety of additional technological weapons.

Initial thoughts were to ‘reboot’ the brain by introducing convulsions, as psychiatrists were convinced MDD was a mental illness that might succumb to clearing it of errata that caused MDD. The first of the convulsive therapies started in 1934 in Hungary. It involved inducing convulsions with Metrazol, the brand name of a compound first introduced as a cardiac drug. Research psychiatrists reasoned that chemically inducing convulsions might somehow mitigate the psychotic symptoms of schizophrenia. Results were good enough to warrant establishing centers in Europe, the Georgia state asylum at Milledgeville, and the Sheppard-Pratt private clinic in Baltimore.

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In the dawn of industrial medicine, it came as a reasonable conclusion that there was an easier way to induce convulsions simultaneously offering a technology upgrade – electricity.  Introduced in 1939 in Rome, Electroconvulsive therapy (ECT) uses an electric current to cause an epileptic seizure for therapeutic purposes.  ECT is probably the most controversial form of treatment in medicine, and certain parts of the world have banned it, although it has enjoyed a recent renaissance as a treatment of MDD.  Regardless, ECT has significant side effects, including memory loss, and is a last-resort treatment.

Current best practices in psychiatry call for a four-step treatment plan, where patients proceed to the next treatment step if they do not achieve complete remission under the current treatment step.  Taking selective serotonin reuptake inhibitors antidepressant drugs is the first treatment step, and as the patient progress through the treatment steps, they try new antidepressant medications with a different mechanism of action, combined with traditional psychotherapy.  Multiple randomized controlled trials and published literature have supported the safety and efficacy of antidepressant therapy.
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Patients that achieve complete remission and tolerate treatment at a specific step then take that drug long-term. However, the four-step program provides a cumulative remission rate of only about 67%.  Enter alternative treatments management of treatment-resistant MDD.
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Research into brain functioning has stimulated interest in research on manipulation of outcomes and curing ailments by electrical stimulation short of ECT, and these efforts have brought forth ‘modern’ methods of electrical brain stimulation such as:

• Vagus Nerve Stimulation (VNS).
• Transcranial Electrical Stimulation (TES).
• Transcranial Alternating Current Stimulation (TACS).
• Transcranial Direct Current Stimulation (TDCS).
• Highdefinition Transcranial Direct Current Stimulation (HD-TDCS).
• Low-field Magnetic Stimulation (LFMS).
• Transcranial Random Noise Stimulation (TRNS).
• Cranial Electric Stimulation (CES).
• Magnetic Seizure Therapy (MST).
• Deep Brain Stimulation (DBS). 

From the new technologies mentioned above, Transcranial Magnetic Stimulation (TMS) is the one that has emerged from the pack and entered the arsenal of psychiatrists to treat the dreaded MDD.  TMS uses a magnetic field to stimulate the brain with electrical currents. TMS requires as many as 36 sessions, typically recommended quickly to reduce the total treatment time.  TMS applies electromagnetic induction to generate an electric current inside the brain without physical contact.

Side effects are generally mild to moderate and improve shortly after an individual session and decrease over time with additional sessions. They may include:

• Headache.
• Scalp discomfort at the site of stimulation.
• Tingling, spasms or twitching of facial muscles.
• Lightheadedness.

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There are many areas of research for the use of TMS aside from treatment of MDD:

• Older adults with mild cognitive impairment which often precedes dementia.
• Chronic prostatitis and chronic pelvic pain syndrome
• Autism spectrum disorder.
• Parkinson’s Disease.
• Suicidal ideation in depression.
• Late life depression
• Schizophrenia
• Epilepsia partialis continua (EPC), a fatal form of epilepsy resistant to medications.
• Obesity and other eating disorders.
• Strokes.
• Substance abuse disorders such as alcoholism and opioid addiction.
• Tourette Syndrome in which an afflicted individual involuntarily blurts random words, often salty.

Various Depression Treatments from Current Opinions in Psychiatry September 2019

The simultaneous application of TMS and psychotherapy in treatment-resistant MDD resulted in a 66% response and a 56% remission rate at the end of treatment with 60% sustained remission at a 6-month follow-up. Most patients undergoing TMS continue to receive antidepressants but the research into synergistic effects of both is sparse.

TMS is an approved and acknowledged treatment for MDD, and the clinical field is rapidly evolving, aiming to optimize response and remission rates for MDD patients.  Most insurance plans cover TMS, provided the patient has treatment-resistant MDD, defined as two or more medications and two years of psychotherapy being ineffective. In addition, new studies are emerging, evaluating fine-tuning individualized treatment protocols.

There remain substantial unanswered questions about TMS:

• Is TMS accomplish long-term remission of MDD, or are there requirements for ‘tune-ups’?
• What is the best sequencing between TMS sessions?
• What is the most practical combination of TMS with other antidepressant treatments?
• Better research on TMS as a cognitive enhancer.
• What are the predictive factors of response?

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Aside from the promising results so far, TMS is a rest stop, not a destination.  The development of treatments is evolutionary, and this is just one step. More critical questions such as other health problems contributing to MDD remain unconsidered in the industrial medicine milieu.  Lowering stress levels and reducing dramatic disparities of income produced by poor governance of uncontrolled capitalism would likely be a better and longer-term fix for the horror of MDD.