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What is Treatment-Resistant Depression?

Updated: Jan 19, 2023

By Ashley Barnes, M.S.

Reviewed by: Mark Hrymoc, MD

When Antidepressants Don’t Work

Depression may have causes we don’t yet understand, which may explain why antidepressants aren’t effective for all. Many people become distressed when they try taking antidepressants to combat their diagnosis, only to realize the medication doesn’t relieve their symptoms.

If you are reading this post and this resonates with you, you're not alone. In fact, antidepressants don’t improve symptoms for around 10-15 percent of people living with depression; additionally, around 30-40 percent observe only partial improvement in depression symptoms (Tundo et al., 2015). When considering all the people in the United States who take antidepressants, that’s so many people experiencing the same struggle!

Treatment-Resistant Depression

In simple terms, Treatment-Resistant Depression (TDR) is “depression that doesn’t respond to antidepressants,” also known as treatment-refractory depression (Healthline, 2022). Someone with TRD may try two or more antidepressant medications such as Selective serotonin reuptake inhibitors (SSRIs) and feel no effect. In other words, if you have tried more than two antidepressants and experienced no effect, you may be living with Treatment-Resistant Depression.

Depression symptoms you may be experiencing include:

  • Depressed mood: feelings of sadness, hopelessness, emptiness.

  • Lack of pleasure: in various activities, even those you love most.

  • Fluctuations in weight: eating more or less than usual.

  • Sleep changes: you may find yourself sleeping more or less than you normally would.

  • Slowing down: you may be observed by others to move and talk slower than usual.

  • Loss of energy: you may experience tiredness and lack of energy.

  • Guilt: this feeling may become excessive and may be accompanied by feelings of worthlessness.

  • Concentration changes: you may have trouble focusing or making decisions.

  • Thoughts of death: some people experience thoughts of suicide or related ideation.

    • If you have any of these thoughts and have an intent to act on them, please contact the National Suicide Prevention Lifeline: 988 for your own safety.

Treatment Options for Treatment-Resistant Depression

Ketamine Therapy has been researched to have a high response rate in Treatment-Resistant Depression with 70% of patients reporting improvement in contrast with only 15% for another oral antidepressant (Trivedi et al., 2006).

Based on sound research, Ketamine Therapy treatment is to be conducted in 6 sessions over the course of three weeks for the best results. After the 6 sessions are completed, patients may schedule “booster sessions.” Though the standard 6 sessions will be consistent across all patients, the route of administration can vary. Routes of ketamine administration that the Ketamine Therapy Center offers include intramuscular injection (IM), intravenous infusion (IV), and nasally (Spravato). Treatment may also involve Ketamine Assisted Psychotherapy (KAP), which involves a psychotherapist sitting in and conducting a therapy session during the ketamine experience.

Ketamine Therapy Center

Ketamine Therapy Center is a treatment branch from the Mental Health Center that specializes in ketamine infusion therapy.

Our doctors offer Ketamine Therapy Evaluations to thoroughly assess patients for ketamine therapy candidacy; from here, they collaborate with patients to develop treatment plans. Our office in the Cedars- Sinai Medical Office towers houses rooms specially designed for patient comfort. Our highly experienced and talented nurses are well-versed in ketamine infusion therapy and help patients feel comfortable as they move through the treatment process. Our therapists are trained in Ketamine Assisted Psychotherapy (KAP) and offer therapeutic guidance to enhance the psychological benefit of the treatment while simultaneously creating a grounded and safe space.

For more information, please do not hesitate to explore our website or contact our office!


Healthline Media. (2020). How to manage treatment-resistant depression. Healthline. Retrieved November 30, 2022, from

Trivedi, M.H., Rush, A.J., Wisniewski, S.R., et al. (2006). Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: Implications for clinical practice. Am J Psychiatry, 163(1): 28–40. doi: 10.1176/appi.ajp.163.1.28.

Tundo, A., de Filippis, R., & Proietti, L. (2015).Pharmacologic approaches to treatment resistant depression: Evidences and personal experience. World J Psychiatry. 2015 Sep 22;5(3):330-41. doi: 10.5498/wjp.v5.i3.330. PMID: 26425446; PMCID: PMC4582308.

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