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Ketamine Therapy: When Antidepressants Fail

By Ashley Barnes, M.S.

Reviewed by: Mark Hrymoc, MD

When Antidepressants Fail

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).

Signs Your Antidepressant Stopped Working

The goal of antidepressant medications is to place depression symptoms in remission - in other words: eradicate depression symptoms. It usually takes antidepressants two to 12 weeks to start working; unfortunately, this doesn’t always happen. Here are some signs that your antidepressant medication is failing you:

  • The drug’s side effects are negatively impacting you (ex: you struggle to sleep even though you are exhausted, you start to have violent mood swings).

  • Your depression symptoms are worsening (ex: it is hard to get out of bed, you feel extra agitated).

  • You experience no relief from your medications (ex: you have been taking an antidepressant for months with no noticed relief from symptoms).

  • You feel energetic but still down and depressed.

Depression Symptoms

The following are depression symptoms that your antidepressant medication may not be helping with:

  • 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-Resistant Depression

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.

Ketamine Therapy 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). The results of a ketamine therapy clinical study published in 2022 found that 89% of participants in the study experienced improvement in symptoms of both anxiety and depression with 63% of participants experiencing more than a 50% reduction in depression symptoms (Hull, et. al, 2022).

Further, Yale researchers have conducted “ketamine research by experimenting with using subanesthetic doses of ketamine delivered intravenously in controlled clinic settings for patients with severe depression who have not improved with standard antidepressant treatments. The results have been dramatic: In several studies, more than half of participants show a significant decrease in depression symptoms after just 24 hours. These are patients who felt no meaningful improvement on other antidepressant medications” (Yale Medicine, 2022).

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

Hull, T. D. et. al, (2022). At-home, sublingual ketamine telehealth is a safe and effective treatment for moderate to severe anxiety and depression: Findings from a large, prospective, open-label effectiveness trial. Journal of Affective Disorders. Volume 314, 1 October 2022, Pages 59-67.

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.

Yale Medicine. (2022). How ketamine drug helps with depression. Yale Medicine. Retrieved January 19, 2023, from

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