Learn about treatment-resistant depression, its symptoms, and effective treatment options like esketamine and transcranial magnetic stimulation (TMS).
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Learn about treatment-resistant depression, its symptoms, and effective treatment options like esketamine and transcranial magnetic stimulation (TMS).

By Bryan Walker, PMHNP-BC

Frequently, I am asked, what is treatment-resistant depression? First, let’s define depression. Depression, in many people’s minds, is sometimes envisioned as someone curled up in a fetal position in the dark, crying. But this is not at all the typical presentation of depression. Depression is an illness characterized by some of the following:

  • Feeling sad or low
  • Having an “empty” mood
  • Feeling anxious
  • Feeling guilty or helpless
  • Feeling worthless, hopeless, or pessimistic
  • Feeling restless, frustrated, or irritated
  • Losing interest in things you once enjoyed
  • Avoiding your usual activities
  • Having less energy and feeling fatigued
  • Moving or speaking slowly
  • Having difficulty paying attention, remembering, or making decisions
  • Having difficulty sleeping, waking up too early, or oversleeping
  • Experiencing unplanned changes in eating habits and weight
  • Experiencing headaches, cramps, digestive issues, or other aches and pains that don’t have a clear cause and don’t get better with treatment
  • Talking about death, having thoughts of suicide, or attempting self-harm

Once a major depression has been diagnosed, if it does not respond to treatment by at least two different antidepressant medications, it can be considered treatment-resistant depression.

Treatment for Treatment-Resistant Depression

In general, the standard for treating depression is to start by treating with a selective serotonin reuptake inhibitor (SSRI). If a patient does not respond to one of these, the provider will likely trial another type of antidepressant that may target different neurotransmitters in the brain, such as epinephrine, dopamine, or Gamma-aminobutyric acid, which is commonly referred to as “GABA.”

If an individual is not responsive to at least two traditional antidepressants, other options become available. Recently, an inhaled form of Ketamine known as esketamine, which goes by the brand name Spravato®, has become available to treat these individuals. Treatment with Spravato has very few limitations on its use. The two biggest limitations from the prescriber side are that the patient’s blood pressure must be less than 140/90, with or without treatment, and they cannot have any current or past history or treatment of an aneurysm.

Individuals treated with Spravato are given a series of doses of the medication in a monitored setting over the course of 8 weeks (about 2 months). Each treatment episode requires a 2—to 2.5-hour commitment to allow for administration of the inhaled medication and monitoring.

In addition to the ability to use Spravato, a novel treatment called transcranial magnetic stimulation, or TMS, is available. TMS therapy is FDA-cleared, with none of the risks associated with general anesthesia or the unpleasant side effects that accompany antidepressants. The therapeutic process takes 3 to 6 weeks, with 40-minute sessions five days per week. The patient is fully alert during the TMS therapy procedure and can easily return to normal daily activities following the sessions.

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