TMS Advances

Beating comorbid major depressive disorder and anxiety

June 14, 2019


In psychiatry, comorbidity is defined as the presence of more than one identifiable psychiatric disorder, as identified in the DSM, in a patient.

In a recent study published in the Journal of Affective Disorders, researchers wanted to find out if rTMS (repetitive transcranial magnetic stimulation) would be effective for treatment-resistant Major Depressive Disorder (MDD) with comorbid anxiety disorders. rTMS has been studied as an effective treatment for MDD alone, but there has been little research done on its efficacy on MDD with comorbid anxiety.

In this article, we will:

  • Define MDD, anxiety, and their comorbidity
  • Show how rTMS works
  • Outline the study and its conclusions

MDD, anxiety, and their comorbidity

Major Depressive Disorder (MDD)

MDD, simply known as depression, is one of the most common, but serious, mood disorders, affecting over 300 million people worldwide—or 10% of the world population—according to the World Health Organization (WHO).

According to the National Institute of Mental Health (NIMH), some of the symptoms of MDD include, but are not limited to:

  • Persistent sad, anxious, or “empty” mood
  • Feelings of hopelessness, pessimism, guilt, worthlessness, etc.
  • Loss of interest or pleasure in hobbies and activities
  • Decreased energy or fatigue
  • Moving or talking more slowly
  • Feelings of restlessness or trouble sitting still
  • Difficulty concentrating, remembering, or making decisions
  • Difficulty sleeping, early-morning awakening, or oversleeping
  • Appetite and/or weight changes
  • Aches, pains, headaches, cramps, or digestive problems without a clear cause
  • Thoughts of death or suicide, or suicide attempts

Individuals are at a higher risk for MDD if they:

  • Have personal or family history of depression
  • Go through major life changes, trauma, or stress
  • Have certain physical illnesses and medications

Anxiety disorders

As is the case with depressive disorders, there are several different anxiety disorders, but the Journal of Affective Disorders’ study was not limited to a certain type of anxiety. It merely tested for the comorbidity of MDD and any anxiety disorder.

Following are brief descriptions of a few kinds of anxiety disorders, as defined by the NIMH.

Alongside depression, anxiety disorders are another very common mental illness. According to the Anxiety and Depression Association of America (ADAA), in the US, anxiety disorders affect 40 million adults (ages 18 or older).

Generalized Anxiety Disorder

Individuals who suffer from Generalized Anxiety Disorder (GAD) have excessive anxiety or worrying for most days for at least 6 months. These may be about a number of things, such as health, work, social interactions, and everyday circumstances. This heavily impacts these individuals’ daily lives.

Symptoms include:

  • Restlessness, or feeling on edge
  • Fatigue
  • Difficulty concentrating
  • Irritability
  • Muscle tension
  • Inability to control worries
  • Sleep interruptions

Panic Disorder

Individuals with panic disorder experience recurring and unexpected panic attacks, or sudden instances of intense fear. Attacks can occur unexpectedly, or as the result of being triggered, from something such as a fear.

During a panic attack, individuals may experience:

  • Heart palpitations or accelerated heart rate
  • Sweating
  • Trembling
  • Shortness of breath, feelings of smothering or choking
  • Feelings of impending doom
  • Feelings of being out of control

Phobia-Related Disorders

A phobia is “a type of anxiety disorder that causes an individual to experience extreme, irrational fear about a situation, living creature, place, or object.”

People with a phobia:

  • Have irrational or excessive worry about the feared thing
  • Take steps to avoid the feared thing
  • Experience immediate anxiety upon encountering the feared thing
  • Endure unavoidable objects and situations with intense anxiety

Here are a few different phobias and phobia-related disorders:

  • Specific phobias (sometimes called simple phobias): phobias about specific types of objects or situations. Some examples include:
  • Flying
  • Heights
  • Animals (e.g. spiders, dogs, snakes)
  • Needles or injections
  • Blood
  • Social anxiety disorder (previously called social phobia): Individuals with social anxiety disorder have an intense fear of social or performance situations. They feel as if they will be negatively perceived by others, which will lead to embarrassment. Thus, many individuals with this disorder avoid social situations. This may occur in a variety of places, such as the workplace or school.
  • Agoraphobia: Individuals with agoraphobia have intense fear of more than one of the following situations:
  • Using public transportation
  • Being in open spaces
  • Being in enclosed spaces
  • Standing in line or being in a crowd
  • Being outside of the home alone

People with agoraphobia often avoid these situations, because they feel as if it will be difficult to leave if they have panic-related reactions.

  • Separation anxiety disorder: Individuals with separation anxiety disorder have fears about leaving people to whom they are attached, which leads them to avoid being separated from these people. They may worry that a harm will come to their attachment figures if they are separated. Although many believe that only children deal with separation anxiety, adults can also be diagnosed with this disorder.

Comorbidity of MDD and anxiety

Results from a WHO Mental Health Survey found that there is a 5.5% prevalence of MDD in developed countries, with the presence of a comorbid anxiety disorder in a staggering 49.7% of these cases.

According to a 2015 article published in the World Journal of Psychology, it was found that, in all likelihood, most comorbidities of anxiety and depression are treatment-resistant. Therefore, a more complicated treatment of pharmacology must be employed. However, rTMS provides a non-invasive, drug-free, alternative to treating comorbid anxiety and depression.

A study by Fava et al. (2008) found that patients with MDD and comorbid anxiety had significantly more disease, reduced remission rates, and greater side effect-burden. In the study, Fava et al. concluded that antidepressants were less effective for individuals with depression and comorbid anxiety as compared to depressed individuals without comorbid anxiety.

Thus, depression with comorbid anxiety was found to be more resistant to treatment than depression alone.

rTMS: What it is, and how it works

What is rTMS?

According to Healthline, rTMS is “a form of brain stimulation therapy used to treat depression and anxiety. It has been used since 1985. The therapy is non-invasive and uses a magnet to target and stimulate certain areas of the brain, making it a  drug-free procedure.

How does rTMS work?

rTMS sessions can last from 30 to 60 minutes at a time.

During sessions, rTMS patients sit or recline while an electromagnetic coil is held against the head. The doctor will place the coil against the forehead, near the area of the brain which regulates mood. Then, magnetic pulses pass from the coil to the brain, which sparks an electric current in nerve cells.

It is thought that this stimulation of nerve cells may reduce depression.

Why is rTMS used?

rTMS is commonly employed as treatment for severe, treatment-resistant—i.e. pharmacology and psychotherapy resistant—forms of depression.

Antidepressants and psychotherapy may be used in conjunction with rTMS.

Also, individuals who are not eligible for electroconvulsive therapy (ECT) may be better candidates for rTMS, since ECT has a higher rate for seizures and requires anesthetic inducement.

The study and its results


The goal of the study was to explore whether rTMS is an effective treatment for individuals who suffer from MDD with comorbid anxiety disorder(s). The main aim was to compare remission rates between individuals who suffer from MDD, with and without comorbid anxiety. Remission is medically defined as the “diminution or abatement of the symptoms of a disease,” or “the period during which such diminution occurs.”


It was found that rTMS is equally effective for patients with and without a comorbid anxiety disorder. The researchers stated that this is a “significant [finding], given that 69% of these clinically referred patients had a comorbid anxiety disorder.”

And since “such comorbid anxiety is common in the treatment resistant depression group, and this comorbidity appears not to reduce rTMS effectiveness, it appears that these patients should still be offered a trial of rTMS in clinical practice.”

Finally, there is conclusive evidence from a study that there is an effective treatment for depression with comorbid anxiety. This is an important scientific discovery in furthering the treatment of patients suffering with such comorbidity and improving their quality of life.


A major limitation of the study was the absence of a placebo group.

Also, the patients examined in the study were referred by private psychiatrists, so they are not representative of all patients with depression.


The examined study has shown that rTMS is an effective treatment for treating depression—whether accompanied by a comorbid anxiety disorder, or not. However, since depression with comorbid anxiety is particularly treatment-resistant, it is a significant finding that rTMS still yields positive results in these cases.

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