The FDA Approval Process for Ketamine Treatment: Why Hasn't It Happened Yet?


The FDA Approval Process for Ketamine Treatment: Why Hasn't It Happened Yet?

Written by

Isha Team


May 16, 2023


October 6, 2023

Ketamine, a powerful anesthetic and analgesic, has been used for decades in clinical settings. In recent years, there has been a growing interest in the use of ketamine for the treatment of mood disorders such as depression and anxiety. While ketamine has shown promise in many studies, it is important to note that it is not currently approved by the US Food and Drug Administration (FDA) for the treatment of depression or any other mental health condition. In this blog post, we will explore the reasons why ketamine treatment is not FDA approved and what the current scientific evidence says about its efficacy and safety.

FDA approval process for drugs

First, it is important to understand the FDA approval process for drugs. In order to be approved, a drug must undergo rigorous testing and clinical trials to ensure its safety and efficacy. The process can take many years and requires significant resources. For a drug to be approved for a specific condition, it must demonstrate a clear benefit over existing treatments and have a favorable safety profile.

Ketamine, however, has not undergone this rigorous approval process for the treatment of depression. This is because ketamine is already approved by the FDA for use as an anesthetic and for pain management. As such, ketamine can be legally prescribed "off-label" by a doctor for the treatment of depression, anxiety, and other mood disorders.

Challenges of clinical trials for ketamine treatment 

Conducting clinical trials for ketamine treatment faces several challenges. One of the main challenges is the lack of standardized protocols for administering ketamine. The optimal dosing, frequency, and duration of treatment have not been fully established, which makes it difficult to compare the results of different studies. Additionally, placebo-controlled trials are complicated by the fact that ketamine has immediate effects that can be easily recognized by both participants and investigators. This means that the placebo effect may be lessened, and blinding of the study may be compromised. Furthermore, there are challenges in recruiting patients who have not responded to other treatments and are willing to try an experimental therapy. Finally, conducting long-term follow-up studies can be difficult due to the high cost and potential for dropouts. Despite these challenges, research into the safety and efficacy of ketamine for depression continues to progress, and more rigorous clinical trials are underway.

In addition to the challenges in conducting clinical trials, another potential reason why ketamine treatment has not yet received FDA approval is related to the economics of drug development. Pharmaceutical companies invest billions of dollars into the development of new drugs, and the process of getting a drug approved by the FDA is lengthy and expensive. The cost of developing a new drug is estimated to be around $2.6 billion, with a large portion of that cost going towards the clinical trials required for FDA approval (DiMasi et al., 2016). Given that ketamine is a generic drug that is already widely available, there may be little financial incentive for pharmaceutical companies to invest in the expensive and time-consuming process of obtaining FDA approval for ketamine as a treatment for depression.

Ketamine has shown promise in many studies as a fast acting antidepressant

Despite not being FDA approved for this use, ketamine has shown promise in many studies as a fast-acting antidepressant. One of the earliest and most well-known studies was conducted by Dr. Carlos Zarate and his colleagues at the National Institute of Mental Health (NIMH) in 2006. In this study, 18 patients with treatment-resistant depression were given a single dose of ketamine. Within hours, more than half of the patients showed a significant improvement in their symptoms, and the effects lasted for up to a week.

Since then, numerous studies have replicated these findings, showing that ketamine can rapidly improve symptoms of depression and reduce suicidal thoughts. In fact, a meta-analysis published in the American Journal of Psychiatry in 2018 found that ketamine had a rapid and robust antidepressant effect, even in patients with treatment-resistant depression.

Despite these promising results, there are still concerns about the long-term safety of ketamine use for the treatment of depression. The most commonly reported side effects of ketamine include nausea, vomiting, and dissociative symptoms such as feeling detached from one's body or surroundings. There are also concerns about the potential for abuse and addiction, as ketamine is a Schedule III controlled substance.

Other evidenced depression treatments

It is important to note that while ketamine has not been FDA approved for the treatment of depression, there are other evidence-based treatments available. These include various forms of psychotherapy such as cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT), as well as FDA-approved medications such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).

For patients who have not responded to these treatments, ketamine may be a viable option. However, it is important to discuss the potential risks and benefits with a qualified healthcare provider before beginning treatment. Additionally, patients should be closely monitored during and after ketamine treatment to ensure their safety and well-being.

In conclusion, while ketamine has shown promise as a rapid and effective treatment for depression, it is not currently FDA approved for this use. Despite this, many healthcare providers prescribe ketamine "off-label" for the treatment of depression, and numerous studies have shown its efficacy. However, concerns about long-term safety and potential for abuse and addiction must be taken into consideration. Patients who are considering ketamine treatment should discuss the risks and benefits with their healthcare provider and explore other evidence-based treatments before making a decision.

However, it's important to note that there are ongoing efforts to develop new, patentable drugs that target the same NMDA receptors as ketamine, but with fewer side effects and longer-lasting effects. These drugs could potentially receive FDA approval and be marketed for the treatment of depression, which could change the landscape of ketamine treatment in the future.


  1. Canuso CM, Singh JB, Fedgchin M, et al. Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study. Am J Psychiatry. 2018;175(7):620-630. doi:10.1176/appi.ajp.2018.17060720
  2. Sanacora G, Frye MA, McDonald W, et al. A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry. 2017;74(4):399-405. doi:10.1001/jamapsychiatry.2017.0080
  3. Krystal JH, Sanacora G, Duman RS. Rapid-acting glutamatergic antidepressants: the path to ketamine and beyond. Biol Psychiatry. 2013;73(12):1133-1141. doi:10.1016/j.biopsych.2013.03.026
  4. Murrough JW, Iosifescu DV, Chang LC, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013;170(10):1134-1142. doi:10.1176/appi.ajp.2013.13030392
  5. FDA. Understanding the Approval Process for New Drugs. Accessed May 15, 2023.
  6. Liu A, Mulder J, Husain M, Adams T, Baer L, Robinson J. FDA Approval of Esketamine for Treatment-Resistant Depression. JAMA Psychiatry. 2020;77(5):463-464. doi:10.1001/jamapsychiatry.2020.0086.

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