Treatment-resistant depression does not respond to antidepressant medications and talk therapy after an adequate period of time (at least six weeks or more). It is not uncommon and occurs in up to an estimated one-third of patients treated for major depressive disorders. New therapies offer these patients effective — and longer lasting — results.

Treatment-Resistant Depression Symptoms

When symptoms persist for several months and the patient has not responded to two or three trials of antidepressants, the general consensus is to define that as treatment-resistant depression. Symptoms may include several of the below:

  • Depressed moods
  • Anxiety
  • Insomnia or changes in sleep patterns
  • Changes in appetite
  • Inattentiveness
  • Low motivation
  • Diminished positive emotions
  • Social withdrawal
  • Pessimistic thinking
  • Suicidal thoughts

Managing Treatment-Resistant Depression

If you have depression symptoms, you should first work with your doctor to try antidepressant medication and talk therapy over a set period of time to see if that helps. Once your provider confirms a treatment-resistant depression diagnosis, the Froedtert & MCW health network offers two distinct therapy options.

  1. Transcranial magnetic stimulation (TMS)
  2. Esketamine therapy

You can repeat both TMS and esketamine therapy if your depression returns after six to 12 months.

Repetitive Transcranial Magnetic Stimulation (TMS)

TMS is a noninvasive way of stimulating the brain in specific locations that can relieve the symptoms of depression. The therapy focuses a magnetic field on the dorsolateral prefrontal cortex of the brain — an area located just beneath the skull and past your forehead. This area shows dysfunctional brain patterns on scans of people suffering from depression. The technique intends to normalize brain function by stimulating this region.

How Does TMS Work?

During treatment, we position a magnetic coil on the scalp over this part of the brain. You may experience a tapping sensation in the treated area or in your forehead. A typical course of therapy involves a 30-minute session, five times a week for six weeks. Patients are generally recommended to continue taking an antidepressant, as it increases the likelihood of success.

This is a safe option with a very low rate of side effects. It is noninvasive (no surgery) and doesn't require anesthesia. There’s no impairment following a TMS session, and you can go back to work afterwards.

Esketamine Therapy

Esketamine is one of the two molecules in ketamine, a drug widely used in anesthesia. While most antidepressants affect serotonin levels, esketamine is thought to target the neurotransmitter glutamate — enabling the brain to create new neural pathways. These new pathways appear to help patients resist the return of depression.

A typical regimen is two treatments a week for one month, then once a week for a second month.

Esketamine Side Effects

The FDA approved esketamine for use as a nasal spray, but it must be administered in a clinical setting where patients can be monitored afterward for side effects like tiredness, mild dissociation or extreme relaxation.

Esketamine Effectiveness

Patients can experience rapid improvement in their depression with esketamine, sometimes in just days. As with TMS, esketamine should be given along with a traditional antidepressant to maintain improvement and prevent relapse.

Depression Medication Strategies

There are some options that your provider may explore before moving forward with one of these therapies. These include:

  • Giving your current medications more time
  • Switching antidepressants
  • Pharmacogenetic testing — predicts your possible response to medication