TMS for Depression: How It Helps

There is no doubt that depression can be serious. Without treatment, it can become debilitating. At its worst, it can cause suicidal thoughts. About 60 percent – or 420,000 of the over 700,000 people who die by suicide each year – have a mood disorder such as depression.

Depression Epidemic

Depression is “common” worldwide, with just under four percent of the global population affected. However these rates are much higher in the United States. In fact, the U.S. has the second highest rate of depression on Earth – tied with Australia and just behind war-torn Ukraine – according to World Population Review 2023.   

The National Institutes of Health tells us that 8.4 percent of U.S. adults had at least one episode of major depression. In women, rates are yet higher – 10.5 percent, versus 6.2 percent of men. It also impacts younger adults more, with 17 percent of 18-to-25-year-olds having experienced major depression.  

“Depression is extremely common in the U.S. and has reached epidemic levels.”

RENEE GOODWIN

What is Depression? 

Depression is not a passing feeling of sadness. Whether it’s losing a job, breaking up with someone, sustaining an injury, or experiencing a financial setback, all of us can feel depressed at times in response to the trials of everyday life. 

Clinical depression, however, is chronic or recurrent and moderate-to-severe in intensity. In fact, people with depression can find it hard to function. They can have trouble getting out of bed, performing their duties at work, and maintaining relationships.  

RELATED: Am I Depressed? Take the PHQ-9 Test

The Depressed Brain vs. Normal Brain 

Mental illness can be misunderstood. It is not a personal choice. It cannot be readily controlled. It is not unique to an individual; in fact, all of us can be vulnerable to a mental illness at some point in life’s journey.

Mental illness arises from differences in the structure or function of the brain. These differences can be genetic, or they can happen in response to an environmental trigger.  

Although the pathophysiology is not completely understood, real, identifiable brain differences have been noted in people with depression.

Dorsal Lateral Prefrontal Cortex (DLPFC) and Depression

Studies have repeatedly shown abnormalities in the DLPFC of people with depression, in particular:

• Decreased activity in the left DLPFC and connection to the anterior cingulate cortex, the amygdala and the insula, areas associated with mood regulation. This has been found to be correlated with “negative emotional judgment”.

• Hyperactivity in the right DLPFC, which is associated with severity of depression symptoms and to “attentional modulation”, or controlling what you pay attention to versus what you do not.  

Even minor damage to the DLPFC can have an effect. Damage to the DLPFC can manifest as:

• Apathy
• Attention Problems (inattention, problems resolving conflicting stimuli, et al.)
• Blunted Emotional Responses
• Decreases in Goal-Directed Behavior
• Emotional Instability
• Inability to Act Decisively
• Inability to Detect Errors
• Increase in Compulsions
• Indifference to Hunger, Thirst and/or Pain
• Lack of Motivation
• Lack of Spontaneity in Behavior and Language
• Repetitive, Compulsive Behaviors

Many of the symptoms above mirror those with depression, including an overriding sense that “nothing is worth doing” and a lack of interest and engagement with the world.

Neurotransmitters and Depression

Neurotransmitters are the chemical messengers of the brain. They are released by nerve cells, called neurons. Their job is to stimulate neighboring neurons, muscle cells, or gland cells. This allows impulses to be passed from one cell to the next, throughout the entire nervous system.

Three main neurotransmitters are involved in regulation of mood, sleep, appetite, and other functions impacted by depression. There are norepinephrine, serotonin, and dopamine.

If dopamine levels are low, a person may feel tired, unmotivated, and unhappy. Patients with low dopamine can also experience memory loss, mood swings, sleep problems, trouble concentrating, and a low sex drive.

Low levels of norepinephrine can cause a variety of health problems, chief among them anxiety and depression.

Low serotonin levels are associated with decreased energy levels, sadness, feelings of hopelessness and mood swings. Sustained low serotonin levels can lead to anxiety, worsening depression, and even suicidal thoughts.

If levels of these vital chemicals are chronically low, the deficit can also affect other areas of the brain with connections to the DLPFC, such as the insula, anterior cingulate, and the amygdala.

The Insula 

The insula is the part of the brain where the mind meets the body. It is always taking the temperature of your life, and its goal is to keep you in a state of balance, or homeostasis. It’s not letting you get too hungry, too thirsty, too hot, or too cold.

 In a 2007 article for The New York Times, Sandra Blakeslee explains the insula’s complex set of functions this way:

“The insula itself is a sort of receiving zone that reads the physiological state of the entire body and then generates subjective feelings that can bring about actions, like eating, that keep the body in a state of internal balance.”

Information gathered from all senses – except touch and spatial awareness – is routed to the insula. Along the way, input is added from the heart, lungs, gut, and other organs. The insula transforms this input into an emotion that prompts a decision.

When you feel hunger, your insula prompts you to eat. You feel thirsty, it goads you to reach for the water bottle. You smell bad food, your nose wrinkles and you feel disgust, thanks to the insula. It even anticipates future events, such as gearing up for cold weather with a physiological response.

“The insula itself is a sort of receiving zone that reads the physiological state of the entire body and then generates subjective feelings that can bring about actions like eating, that keep the body in a state of internal balance.”

SANDRA BLAKESLEE

Studies have found a link between Major Depressive Disorder and abnormalities of the insula, including:

• Decreased activity in the insula when attuning to internal states. Subjects in one study were shown the words “heart,” “stomach,” or “bladder” in order to turn their attention to those areas of the body. In those with depression, insula activity dropped compared to healthy controls.  
• Increased connectivity between the insula and the limbic system in a resting state – and this is associated with the severity of depression symptoms. The more “functional connectivity” there is, the more severe the symptoms are.
• A greater volume of grey matter, which correlates with higher scores on depression scales
• Decreased functional connectivity between the DLPFC and the insula, which is associated with more severe depression scores.

MDD and its physical symptoms – such as lack of energy, pains and aches, trouble sleeping or oversleeping, and over or under eating – are associated with abnormal recognition of how the body feels – call interoception, for which the insula is responsible.

One study revealed that, in depression, the processing of emotions was shifted to the same region where pain is processed, possibly accounting for the feeling of emotional pain that people with depression experience.

Further supporting this link is a study of Parkinson’s patients published in 2020 which found that severely damaged insula networks in these patients contributed to depression. A damaged insula can also cause a loss of libido, the ability to discern whether a food is fresh or spoiled, and apathy.

The Anterior Cingulate Cortex & Depression

With connections to the thinking brain (prefrontal cortex) and the feeing brain (limbic system), the anterior cingulate cortex acts as a go-between to the two regions. It is responsible for higher-level functions such as:

• Anticipating a Reward
• Allocating Attention
• Autonomic Nervous System Response
• Controlling Impulses
• Detecting Error
• Emotional Awareness & Expression
• Ethics and Morality
• Impulse Control
• Making Decisions
• Managing Pain
• Monitoring Performance

It is especially critical for controlling and managing our emotions, which is an important part of treating depression. Problems with the anterior cingulate cortex (ACC) are associated with feeling depressed as well as persistent feelings of sadness. 

There are two main regions to the ACC: the pregenual (pACC) and subgenual or subcallosal (sACC) regions. Brain differences in the latter have been found in those with MDD versus those without. In particular:

• The subgenual ACC is smaller in people with depression; however, activity is proportionately greater, given its size. This increased activity can be found when people experience sadness in a “baseline resting state” – and the more activity there is, the greater degree of sadness is felt. What’s more, hyperactivity here can predict whether someone will experience treatment-resistant depression.
• There is less functional connectivity between the two parts of the ACC (pACC and sgACC), which can be the reason that negative emotions persist with depression.

In simple terms: If you find it hard to break out of negative emotions and are constantly ruminating on the negative (“bad things always happen to me”, etc.) that’s happening in the ACC.

The Amygdala & Depression

Two almond-shaped organs collectively called the amygdala are nestled on either side of the brain. They act as our emotional center, playing a role in:

• Emotion Generation & Response
• Perception of Emotions
• Interpreting What is Going on Around us
• Autonomic Responses
• Directing Attention
• Emotional Memory Formation
• Fear Conditioning

In short, the amygdala is responsible for how we feel about the situations and events of our lives. It is also always on the lookout for potential threats, continuously scanning our surroundings for them, then sending messages to the PFC and ACC that trigger an immediate emotional response. You aren’t sure why you are feeling fearful or panicked, but you picked up something in the environment – such as an angry facial expression – that triggered the amygdala’s fight-or-flight response.

In people with depression:

• The amygdala is larger and overactive. This can lead to overwhelming negative emotions, a hard time “shutting your brain off” to rest, and an inability to cope with the stress of everyday life. Because the amygdala is more oriented to negative stimuli, overactivity here can lead to a negative bias, or a tendency to view the world in a not-so-favorable light.
• There is decreased connectivity of the amygdala to other areas of the brain controlling emotions. This further enforces the experience of overwhelming emotional states as well as “impaired social cognition,” or the ability to properly interpret and store information about people around us, as well as an outsized response to negative cues.

How TMS Works for Depression

The connections between a disruption in neurotransmitter production and its effects on multiple areas of the brain with depression are obvious. These chemicals are vital for a healthy brain and good mental health.

Many anti-depressants on the market aim to increase levels of one or more of these neurotransmitters. For those with treatment-resistant depression, however, those medications fail to make a real difference in symptoms.

That’s where TMS comes in. TMS helps correct the symptoms of depression by stimulating the areas of the brain that produce these chemicals.

TMS Targets the DLPFC and Its Network

TMS works by targeting the DLPFC, which is underactive in depression and very close to the surface of the scalp. It responds to the magnetic stimulation of the TMS machine, and its connectivity to other regions allows TMS treatment to effectively reach those other structures as well.

TMS magnetic coils generate magnetic fields similar to those produced by MRI (magnetic resource imaging) equipment. However, the TMS field is much smaller and more concentrated, targeting an area just two to three centimeters in size.

The brain responds to this stimulation by generating small electric currents that encourage neurotransmitter production – including the same ones lacking in those with depression… dopamine, norepinephrine, and serotonin.

TMS Retrains the Brain

Over the course of treatment, TMS causes the brain to form new neural pathways. Neurotransmitter levels return to normal and, over time, the brain is “trained” to stay in this state.

Patients begin to experience better moods, lessened anxiety, more pleasurable feelings, and feel more motived. Energy levels are boosted and physical symptoms such as aches and pains are alleviated.

It’s not that you will never need TMS again, but, unlike medication, its effects do last longer than treatment duration. In fact, more than a year of symptom relief is the typical response.

TMS Success Stories

It’s always helpful to hear first-hand accounts about a promising treatment. Over the 15 years that TMS has been used for depression, many success stories have accumulated. Here are but a few:

This is but a handful of the many TMS success stories that are out there. The important thing to remember, though, is that research backs up the good results.

What the Research Says About TMS

These benefits of TMS treatment have been confirmed by many clinical studies. Most promising among them is a recent study of 103 TMS providers treating over 5,000 participants. Researchers found that up to 82 percent responded to treatment, meaning that participants experienced improvement in depression symptoms. This is in line with the typically quoted success rate on TMS provider websites, which fall in the 70 to 80 percent range.

What’s more, in the study, up to 62 percent of those 5,000 people experienced total remission. This means that their depression symptoms resolved completely.

“Superior” clinical outcomes tended to be achieved in women and those who received more treatment pulses per session.

Post-Partum Depression

TMS works for post-partum depression as well. One study found that nearly 82 percent of those receiving TMS treatment responded to it, versus 46 percent of the group receiving sham (the procedure equivalent of a placebo) treatment.  

Another study found eight out of nine sufferers experienced remission from post-partum depression with repetitive TMS (rTMS). Seven of the nine also stayed in remission, without the use of medications.

TMS is FDA-Cleared & Covered by Insurance

TMS has been cleared by the US Food and Drug Administration for use in major depressive disorder and covered by a wide range of insurance providers.

Both private carriers such as Blue Cross Blue Shield and as well as government plans, including Medicare Part B and Tricare, cover TMS sessions, subject to deductibles and copays.

Patients must meet the criteria, of course. Typically, they must have tried at least two antidepressants without success. An estimated one-third to one-half or more of people with Major Depressive Disorder fit into this category.

Why Should We Care About TMS for Depression?

Depression is one of the leading causes of disability worldwide. It has been described as a black cloud, a heavy weight, and a feeling of separation from others. It can cause severe impairment in an individual’s life, as well as affecting those surrounding them, and increase the risk of suicide.

Depression Affects All the Lives it Touches

It’s not just the person who has depression who suffers. Their loved ones, their children, their friends, their employers and their co-workers are affected by it as well. People with depression also tend to earn less on the job, which affects those who are dependent upon them.

As if that weren’t enough, the economic cost of depression was estimated at a staggering $236 billion five years ago – a 35 percent increase over 2010 estimates. This includes:

• Direct costs of treatment, from counseling to medication and ER admissions
• Costs to employers, including missed workdays and reduced productivity
• The cost of suicide

This does not include raised prices from businesses to make up for their losses due to depression. For every dollar spent on direct treatment, it costs all of us another $2.30 on indirect expenses.

Without a doubt, though, it’s the high human cost of depression through debilitation and suicide that is truly devastating.

Hope for Treatment-Resistant Depression

If I can stay in bed all day, that’s what I do… I just want to be able to live my life.”

RINI KRAMER CARTER, IN AN INTERVIEW WITH PBS

Rini Kramer-Carter told PBS her treatment-resistant depression severely affects her life, causing her to sleep as much as 20 hours a day. “If I can stay in bed all day, that’s what I do… I just want to be able to live my life.”

Unfortunately, she is not alone. Up to 60 percent of people with depression do not adequately respond to first-line treatments of therapy and medication.

Treatment resistant depression can be challenging, as patients have already experienced:

• A lack of response to treatment
• After a minimum of two trials of two different anti-depressant medications
• For a minimum of four to six weeks each

Due to an ongoing nationwide shortage of psychiatrists in the United States, most people are seen by primary care doctors, who are overwhelmed with patients already. Over 50 percent of the counties in the U.S. do not even have one psychiatrist.

“Given a shortage of geriatric psychiatrists, decisions on treatment are often left to primary care providers, who may not have relevant training or might be reluctant to take on such complicated care,” said Evelyn Whitlock, Patient-Centered Outcomes Research Institute’s Chief Science Officer, said. “They try something, and, if it doesn’t work, they try something else… trial and error is not ideal”

There is a compelling need for new treatments to counteract treatment-resistant depression, and TMS fits that bill. It is clinically proven effective, safe, and FDA cleared to tackle this hard-to-treat condition.

While locally sponsored efforts are now underway to educate primary care providers and their patients about TMS, it remains a treatment promise that, much more often than not, delivers real results to depression sufferers who need it most.

About the Author

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