What is Treatment-Resistant Depression?
By Gia Nevel, PMHNP
Treatment-Resistant Depression is a form of Major Depressive Disorder in which individuals do
not respond to traditional therapies. Depression can significantly reduce one’s quality of life,
making everyday tasks seem impossible. For many, traditional treatments like talk therapy and
antidepressants provide relief. However, for a significant subset of individuals, up to thirty
percent of individuals with depression6, these interventions don’t yield the desired results,
leading them into the complex territory known as Treatment-Resistant Depression (TRD).
There is some debate on the parameters for diagnosing depression as Treatment-Resistant. The
generally accepted definition is an individual with major depressive disorder who does not
experience a sufficient therapeutic response after trying at least two different antidepressants
from different classes at the appropriate dose and duration.
What is a therapeutic response?
A therapeutic response is generally defined as a 50% or greater reduction in symptom severity
as measured on a symptom-reporting scale.4 A failed response is considered less than a 50%
reduction in symptom severity. However, the exact definition of treatment-resistant depression
is relatively narrow. For instance, is a 75% response adequate? For some, the pervasiveness of
symptoms at this level may still be intolerable and drive them to seek alternate treatment
modalities despite not falling into the parameters of treatment-resistant depression.
A Glimmer of Hope: Ketamine’s Role
Ketamine is a dissociative anesthetic used since the 1970s for anesthesia and pain relief.
Esketamine, a form of Ketamine, was designated a Breakthrough Therapy by the FDA in 2013
when preliminary clinical evidence showed it could significantly alleviate symptoms of
treatment-resistant depression and halt suicidal ideation.
Breakthrough Therapy designation allowed Esketamine to undergo an expedited review process
for FDA approval as a therapy for treatment-resistant depression. Ketamine’s antidepressant
effect has been described as one of the most critical discoveries in psychiatry in the past
century.3
An important consideration for clinicians managing treatment-resistant depression is patient–
reported outcomes (PROs), the patient’s subjective reports on their quality of life and
psychosocial functioning. PROs go beyond symptom reduction and focus on well-being.7
Individuals who have undergone ketamine therapy report:
- Greater insight
- Joy
- Positivity
- Emotional connectivity
- Mindset shifts
- Lifting of mood
- Improved motivation
Traditional therapies, such as antidepressants, can take weeks to have a noticeable effect. In
contrast, ketamine can alleviate symptoms within hours to days, offering a faster reprieve from
depressive symptoms. Ketamine can act as a bridge to help individuals with severe symptoms
while they wait for their antidepressant to take full effect.
Some individuals achieve remission of their depressive episodes after a series of treatments.
Others find they have significant improvement, allowing them to reduce their dosages of
antidepressants or other medication. Patients frequently struggle with taking SSRIs due to side
effects such as emotional blunting, cognitive dulling, weight gain, and sexual dysfunction.
Ketamine is compatible as an adjunctive treatment because it doesn’t have the same side effect
profile, improving treatment tolerability.
The immediate mood-lifting effects of ketamine are typically two to seven days; however,
ketamine’s impact on synaptic plasticity may have long-term positive effects on mood and
cognition. As a result, Ketamine may help individuals experience fewer recurrences of
depressive episodes following ketamine treatment.
While psychedelic therapies such as ketamine represent an innovative frontier in treating
depression, it’s essential to weigh their benefits against potential risks, recognizing they are not
fit for all. As our understanding of treatment-resistant depression evolves, therapies such as
ketamine provide hope.
If you or your loved one are suffering from depression, ketamine therapy may be a great next step for you. Feel free to call Kure Medical or your local ketamine center to learn more about ketamine infusion therapy. If this is an emergency please call the National Mental Health Hotline: 988 or call the National Emergency Hotline: 911
Disclaimer: This blog is for informational purposes only and does not constitute medical advice. Please consult with a healthcare professional for personalized recommendations and guidance regarding ketamine therapy.
