In this article, we will discuss some of the biology of depression, the effectiveness of traditional treatments, and the role of other options, including transcranial magnetic stimulation (TMS), for depression.

Neuroscience of Depression

Depression involves many neuroanatomical structures including but not limited to: the dorsolateral and ventromedial regions of the prefrontal cortex (PFC). The prefrontal cortex is involved in managing factors in psychiatric health such as

  • suicidality
  • feelings of worthlessness and guilt
  • pleasure/interest
  • concentration
  • fatigue (both physical and mental)
  • psychomotor manifestations

Research shows that the ventromedial PFC communicates with other parts of the brain involved in reward pathways and regulating emotion. Whereas the dorsolateral PFC links to areas that involve abstract logic, making goals, and memory. These deeper links play other roles in symptoms of depression such as:

  • emotion regulation
  • appetite
  • sleep
  • internal drive
  • focus

First-Line Treatments and Evidence Behind Them

Depression is complex and unique to each individual. The initial line of treatment, which indeed can be effective for many is to start medication with a combination of therapy. Now, these interventions do cause therapeutic neuroanatomical changes in the brain, but for many, it is insufficient. Given the complexities involved in each person’s case, it does take some trial and error before finding an effective regimen, which can be discouraging to some. As a matter of fact, about 1 in 3 patients exhibit findings suggesting they have treatment resistance and they fail to respond to up to several different approaches.

The Star*D Trial

This was conducted in 2010 and is one of the most comprehensive studies done on depression treatment. It involved over 2800 patients and was done over 6 years. All patients were initiated with some form of treatment for depression. For those with insufficient response, they went into the next level of treatment (e.g. using an augmenting medication, adding cognitive behavioral therapy, etc.). Those who continued to have limited response were then moved into the next level of treatment and there were a total of 4 levels of treatment. After two levels of treatment, about half the patients achieved remission. However, about 1/3 of patients after going through all 4 levels of treatment were still not in remission.

TMS Therapy

To date, over 40 studies have evaluated the efficacy of TMS for depression. Many were multi-site trials as well as meta-analyses. These have shown TMS to be a safe and highly effective treatment.

One of the biggest studies is the NIMH Trial and involved 190 patients with major depressive disorder (MDD). It was placebo-controlled and found that those getting active treatment had a remission rate 4 times higher than the placebo group. Similar findings were made in another randomized controlled trial involving 301 patients. This data was pivotal in TMS getting FDA approval as a treatment for depression. Another exciting more recent trial is that of Brainsway which involved 20 sites worldwide and enrolled 212 patients with 181 completing the study. The remission rate was even higher than NIMH and Neuronetics trial, as a matter of fact, approximately double. What is more exciting is that a recent head-to-head study between the H1 coil used by Brainsway and the figure of 8 coil showed that the H1 coil indeed is more effective and reached statistical significance. So not only is TMS an effective treatment option, but the type of TMS makes a difference as well.

The Safety of TMS

Another benefit of TMS is that it has fewer side effects than most other biological treatments for depression. The most severe potential side effect is that of inducing a seizure. However, it is estimated that this occurs in 1/30,000-1/60,000 treatment sessions. In addition, many of the seizures reported in the literature also had comorbid positive testing for alcohol or substance use during treatment which is one reason abstinence is heavily recommended. Also, active alcohol use can potentially decrease the efficacy of TMS. The most common side effects though are mild scalp discomfort or headaches which greatly attenuate by the second week of treatment.

Other Treatments

Electroconvulsive (ECT) therapy is still shown to be the most effective treatment for depression to date. Although it gets a bad reputation from media, as in many other aspects of medicine, it works well for the right candidate. If someone is experiencing depression to the point of catatonia, active suicidal ideation, psychosis, or bipolar depression, ECT really has more robust evidence supporting it than TMS. And yes, ECT does have a higher remission rate than TMS. But then again, it all depends on that individual person’s case. Some individuals may be at higher risk for ECT based on medical conditions as the treatment involves the use of anesthesia. Also, ECT requires some time away from work as the patient cannot drive back home on their own immediately after treatment.

Ketamine has also gained attention. The FDA recently approved esketamine for augmentation for treatment-resistant depression. However, results are relatively modest and in those over 65, esketamine was not found superior to placebo. In addition, there is addiction or abuse potential. However, probably the biggest high point of ketamine is that it has been found to be helpful in reducing acutely intensifying suicidal ideation which helps providers buy more time until a maintenance regimen is established.

Psilocybin, the active ingredient in magic mushrooms, has actually shown more promise and is actively studied at the University of Wisconsin-Madison and many other sites. It may have more promise even than ketamine as preliminary studies have shown a robust effect size AND durability of benefit.

Finally, let’s not underestimate evidence-based therapy. Many times when I encounter patients, unfortunately, most of them have not experienced the various therapy modalities which still remain highly effective and show sustained if anything enhanced effect over time. Sometimes it takes over a year, but literature has demonstrated again and again that it is a powerful tool. The most heavily studied are cognitive behavioral therapy, interpersonal therapy, and dialectical behavioral therapy. For those with posttraumatic stress disorder (PTSD), patients may benefit from cognitive processing therapy (CPT), prolonged exposure therapy, and eye movement desensitization and reprocessing (EMDR).

If you are wondering if TMS is right for you, contact us today. Not only can we walk through any questions you may have, we are the only practice in the Milwaukee area that offers the highly effective H1 coil.