At least 1/3 of people with depression do not achieve full recovery from depression with medications and psychotherapy (talk therapy). This proportion may be even higher. When a person does not have a full remission from depression with one or two antidepressant trials, they are considered to have “treatment resistant depression,” or TRD.

The seminal STAR-D study (Sequenced Treatment Alternatives to Relieve Depression), completed in 2004, was the largest prospective clinical trial of major depressive disorder ever conducted. In STAR-D, participants with major depression were aggressively treated with successive antidepressant medications and augmenting agents and monitored for response.

If they did not achieve a full remission with the first-line treatment, they progressed to the next level, either switching to a new antidepressant agent or adding an augmenting agent to their regimen.

If depression did not remit with the second level treatment, they progressed to level three, again either switching to a new antidepressant from a different class or adding a different augmenting agent.

In total, there were four levels in STAR-D, with more aggressive pharmacologic treatment at each level. STAR-D showed diminishing clinical benefit and increasing side effect burden with each successive medication trial. 

There are several key takeaway points from STAR*D as people with depression move through medications trials: 

  • The likelihood of achieving remission DECLINES from 27.5% with first-line medication treatment to only 6.9% with fourth-line treatment. 
  • The likelihood of discontinuation of a medication rises from 8.6% with first-line medication treatment to 41.4% with fourth-line treatment, due to increased side effect burden. 
  • The longer patients took the same antidepressant medication, the less effective it became over time—even if it was taken exactly as prescribed. 
  • The side effects of the ineffective medications ended up making depression worse in many participants. 

TMS is an alternative to antidepressant medications and offers several advantages over other brain stimulation techniques. It is non-invasive, meaning it does not require surgery or anesthesia.

Unlike electroconvulsive therapy (“shock therapy”) a person getting TMS is awake and alert during the treatment and can drive themselves to and from appointments and return to everyday activities immediately after the treatment; there are no cognitive side effects associated with TMS.  In fact, TMS is actively being investigated for the treatment of cognitive disorders, including mild cognitive impairment (a diagnosis given to those in a predementia state).

TMS is well-tolerated, with mild side effects, such as scalp discomfort or headache, being the most common; these tend to be mild and respond to over-the-counter pain medications, if needed.

Compared to medications, TMS poses a lower risk of systemic side effects, as it directly targets the brain region of interest.  In comparison, a daily antidepressant such as a selective serotonin reuptake inhibitor (SSRI) increases serotonin throughout the body, including the GI system, which can cause unpleasant gastrointestinal side effects such as nausea, vomiting or diarrhea; these medications can affect other neurotransmitter systems, as well, and cause well-known unwanted side effects including dry mouth, sweating, sexual dysfunction, or weight gain. Many people also notice a blunting of positive emotions, or feeling “flat,” while on antidepressants.  

TMS is a well-established treatment for major depressive disorder.

TMS has been cleared by the U.S. Food and Drug Administration (FDA), for the treatment of major depressive disorder. The first FDA-cleared TMS coil came to the US market in 2008. Since then, multiple TMS devices with different coil designs have gained FDA-clearance for the treatment of depression, and a smaller number of coils have gained FDA-clearance for the treatment of obsessive-compulsive disorder. One coil has gained FDA-clearance for aiding in smoking cessation.