FDA Call to Action: Drug Repurposing to Address Unmet Medical Needs

On May 11, the U.S. Food and Drug Administration (FDA) announced that it is soliciting input from the medical community and the public on opportunities to repurpose existing medications to address unmet medical needs across a range of diseases and conditions.

This development is significant for Ember Health and our broader community, as we believe that an on-label indication by the FDA for IV ketamine in the treatment of depression could strengthen public understanding of its clinical legitimacy and accelerate broader insurance coverage. This article provides context on the FDA’s announcement and outlines how our community can join us in advocating for expanded access to one of the safest, most evidence-supported, and effective treatments available for depression.

Jump To:

• How to Post a Comment
• Suggested Structure for Patient Comments
• Suggested Structure for Mental Health Provider Comments
• Suggested Structure for Family / Loved One Comments
• Reference

Historical Context

Ketamine was first developed in the 1960s, and received FDA approval as an anesthetic in 1970. Since then, it has become one of the most widely used anesthetics in the world (source). After its patent expired in 2002, ketamine became available as an inexpensive generic medication. Since 1984, it has been listed on the World Health Organization’s Model List of Essential Medicines, and remains an important tool in surgical, emergency, and critical care settings globally (source).

Over the past 25 years, researchers have extensively studied intravenous (IV) ketamine at sub-anesthetic (low) doses as a rapid acting treatment for depression. During that time, ketamine has become the most studied medication for depression, by number of clinical trials (source). Clinical data consistently show that IV ketamine alleviates depressive symptoms in approximately 70% of people with treatment-resistant depression (source, source, source). By comparison, SSRIs - the most commonly used pharmacological treatment for depression - show efficacy rates of roughly 35% and often require weeks to take effect (source).

Despite the strength of the evidence, IV ketamine remains an off-label treatment for depression. This is not unusual in psychiatry, where off-label prescribing is common and often supported by substantial clinical evidence (source, source, source). Physicians, including the medical team at Ember Health, may legally and safely administer drugs such as IV ketamine off label using their clinical judgment and discretion.

Ketamine's off-label status for depression nevertheless has important consequences for both public perception and insurance coverage. When a medication receives FDA approval for a specific indication on-label, it creates clearer pathways for reimbursement by public and private insurers, and often leads to a consensus amongst medical providers about the legitimacy of the treatment. To date, however, there has been no established pathway for securing an on-label depression indication for generic medications, including ketamine, despite the growing body of supporting evidence for new uses of the old medications (source, source, source).

When we first launched Ember Health, we assumed that obtaining an on-label indication for a treatment with such compelling evidence would be relatively straightforward. We learned over the years that the FDA has historically lacked a real mechanism for adding new indications to generic medications that were originally approved for other uses. Legal experts similarly advised us that there has been no well-defined pathway for pursuing such a designation.

The FDA Announcement: Why It Matters

The FDA’s announcement earlier this month may represent an important opportunity to change our field.

Recognizing that existing medications may have valuable new uses, including new indications, patient populations, or treatment contexts, the FDA is seeking input from clinicians, researchers, patients, and the public regarding opportunities for drug repurposing that could improve health outcomes.

For Ember Health and the many people whose lives have been improved by IV ketamine treatment, this creates an important opportunity to advocate for ketamine receiving an on-label indication for depression.

The potential implications are significant. IV ketamine’s off-label use for depression is often cited by insurance companies as the main reason that they do not cover treatment in-network. As a result, patients often have to pay out of pocket, or rely on complex out-of-network benefits to pay for treatment. While some individuals can afford an initial course of treatment, for many the ongoing maintenance care many patients clinically require can become financially out of reach.

In addition to the financial implications with insurance, we frequently hear from patients who are hesitant to pursue care because of the stigma associated with “off-label” medications. Despite a large and growing evidence base, confusion and misinformation about IV ketamine remain common. An FDA-approved indication for depression could help reinforce what clinicians and patients already know: when administered in an appropriate medical setting, IV ketamine is a safe, legitimate, and effective treatment option.

At Ember, our mission is to define and expand access to the gold standard of IV ketamine care for depression. We believe this will require broader insurance coverage so that treatment becomes a routine healthcare expense rather than a significant out-of-pocket burden. If the medical community, patients, advocates, and the public can make a compelling case for an on-label indication, it could become one of the most important steps toward expanding access nationwide.

The Opportunity and a Call to Action

The FDA is calling for comments from the public by 11:59 p.m. Eastern Time on Thursday, June 11th, 2026.

Ember Health is submitting a letter to the FDA advocating for the on-label indication of IV ketamine for depression in partnership with the American Society of Ketamine Physicians, Psychotherapists & Practitioners (ASKP3). We are also inviting members of our community, including patients, loved ones, provider partners, and anyone whose life has been affected by depression or ketamine treatment, to make their voices heard.

If you would like to participate, we have provided template letters below that can serve as a starting point for your advocacy. We have also included step-by-step instructions for submitting comments to the FDA, including options for anonymous submission.

We don’t know how the FDA will ultimately respond to this request for public input. We do know, however, that opportunities like this are rare. We are committed to pursuing every available avenue to expand access to one of the most effective treatments available for depression ever discovered, and we invite our community to join us in that effort.

Submit Your Thoughts to the FDA

1. See here the FDA’s official request for information to repurpose existing drugs for unmet medical needs, with full instructions on how to submit your comments
2. The FDA directs people to this form which is a request for information for public comments on Drug Repurposing for Unmet Medical Needs
3. In the form, you’ll see the following sections:
   a. Comment - You can type / paste your full set of comments here, where you have a 5,000 character limit
   b. What is your comment about?
   - Patients and loved ones, select “Individual Consumer”
   - Providers select “Health Professional”
4. Attach files: If you’d prefer to write your comments or include images and save as a PDF, you can upload the file here.
5. Email address
6. Tell us about yourself - you may state “individual” or “an organization” if you are writing on behalf of one of our partner mental health practices. If you put “anonymous”, you do not need to provide an email address in the prior question
7. Either:
   Press “I am not a robot” and then the blue “submit” button
   OR
   Check the box beside "I read and understand the statement above." and then "Submit Comment"

Please do not include private information you would not want posted publicly. FDA states that electronic comments, including attachments, will be posted to the docket unchanged unless submitted through the confidential written/paper process described in the Federal Register notice.

If you'd like to use a template for submitting your comments that follows FDA guidelines:‍

• Suggested Structure for Patient Comments‍
• Suggested Structure for Mental Health Provider Comments‍
• Suggested Structure for Family / Loved One Comments

Suggested Structures for Comment Submissions

Suggested Structure for Patient Comments

→ See here for detailed instructions on how to post a comment.

The most helpful comments are specific, personal, and focused on how IV ketamine treatment has affected your life. Consider addressing the following topics:

1. Why you are writing

I am submitting this comment in response to FDA Docket No. FDA-2026-N-4492, “Drug Repurposing for Unmet Medical Needs.” I am a patient who has received intravenous ketamine treatment for depression, and I am asking FDA to evaluate IV ketamine as a candidate for drug repurposing for treatment-resistant depression and related severe depressive illness.

I understand that ketamine is already an FDA-approved medication for other uses, but IV ketamine for depression remains an off-label treatment. Based on my experience, this off-label status creates real barriers for patients, even when the treatment is prescribed and administered by qualified medical professionals in a structured clinical setting.

2. Your history with depression

Describe:

• How long you have struggled with depression
• Medications you have previously tried
• Other treatments you pursued (therapy, psychiatry, hospitalization, intensive outpatient programs, etc.)
• The impact depression had on your daily life, relationships, work, or ability to function

3. Why you pursued IV ketamine treatment

Describe:

• What led you to consider IV ketamine
• Why previous treatments were not sufficient
• What concerns or expectations you had before starting treatment

4. Your experience receiving treatment

Describe:

• How long you have been receiving treatment
• The safety and medical oversight you experienced
• Any changes you observed in your symptoms, functioning, or quality of life
• Improvements reflected in measures such as PHQ-9 scores, if applicable

5. The impact treatment has had on your life

Describe:

• Relief from depressive symptoms
• Changes in your relationships, work, parenting, or daily activities
• Specific ways treatment has improved your ability to participate in life

Concrete examples are especially valuable.

6. The challenges of maintaining care

Describe:

• The frequency of your maintenance treatments, if applicable
• The financial burden of ongoing treatment
• Any difficulties obtaining insurance coverage because IV ketamine remains an off-label treatment

7. Why FDA recognition would matter

Describe:

• In your opinion, how an on-label indication for depression could affect your ability to access care
• Why broader access to this treatment could benefit patients with treatment-resistant depression
• Why you believe your experience is relevant to the FDA's consideration of unmet medical needs

Close by thanking the FDA for considering your experience and perspective.

‍

Example Patient Comment

I am submitting this comment in response to FDA Docket No. FDA-2026-N-4492, “Drug Repurposing for Unmet Medical Needs.” I am a patient who has received intravenous ketamine treatment for depression, and I am asking FDA to evaluate IV ketamine as a candidate for drug repurposing for treatment-resistant depression and related severe depressive illness.

I understand that ketamine is already an FDA-approved medication for other uses, but IV ketamine for depression remains an off-label treatment. Based on my experience, this off-label status creates real barriers for patients, even when the treatment is prescribed and administered by qualified medical professionals in a structured clinical setting.

I am a patient who has received IV ketamine treatment for depression, and I would like to share my experience.

I have struggled with depression for more than 15 years. During that time, I tried multiple antidepressant medications, psychotherapy, and psychiatric care. While some treatments provided temporary relief, I continued to experience significant depressive symptoms that affected my work, relationships, and overall quality of life.

After exhausting many conventional treatment options, I decided to pursue IV ketamine treatment. I began receiving IV ketamine care in 2023.

My experience has been overwhelmingly positive. Throughout treatment, I have received individualized care with continuous medical monitoring from trained healthcare professionals. Since beginning treatment, I have experienced a significant reduction in my depressive symptoms. My PHQ-9 score decreased from 21 before treatment to 6 after treatment, and I have maintained those improvements with ongoing care.

Most importantly, the treatment has allowed me to participate fully in my life again. I have more energy, stronger relationships, and a renewed ability to engage in work and daily activities. For the first time in many years, I feel hopeful about my future.

To maintain these benefits, I receive booster infusions every six weeks. While the treatment has been transformative, the cost of ongoing care presents a significant challenge. Because IV ketamine remains an off-label treatment for depression, my insurance coverage has been denied, leaving me responsible for substantial out-of-pocket expenses.

An FDA-approved indication for depression could help expand access to this treatment for patients like me who have not found relief through conventional therapies. My experience demonstrates that IV ketamine can be delivered safely under medical supervision and can provide meaningful, lasting improvements for individuals living with treatment-resistant depression.

Thank you for considering my perspective and experience.

Suggested Structure for Mental Health Provider Comments

→ See here for detailed instructions on how to post a comment.

1. Introduce yourself and your practice

Describe:

• Your profession (psychiatrist, psychologist, therapist, social worker, psychiatric nurse practitioner, etc.)
• Years in practice
• Patient populations served
• Experience treating depression

2. The unmet need you see in practice

Describe:

• How common treatment-resistant depression is among your patients
• Limitations of existing treatment options
• The consequences of persistent depression on patients' lives

3. Your experience with IV ketamine

Describe:

• How long you have been referring patients for IV ketamine treatment
• The types of patients you typically refer
• Why you consider IV ketamine when other interventions have been insufficient

4. Outcomes you have observed

Describe:

• Improvements in mood and functioning among referred patients
• Reductions in suicidality, symptom burden, or disability, where applicable
• Any patterns you have observed regarding patient response

Concrete examples are especially helpful.

5. Safety and care coordination

Describe:

• Your experience coordinating care with ketamine providers
• The medical oversight and monitoring your patients receive
• Any observations regarding patient safety

6. The impact of off-label status

Describe:

• How lack of insurance coverage affects your patients
• Instances where patients could not access or continue treatment due to cost
• How greater access could benefit individuals with treatment-resistant depression

7. Why FDA recognition would matter

Describe:

• Why you believe IV ketamine addresses an unmet clinical need
• How an on-label indication could improve patient access and continuity of care
• Why your clinical experience supports further recognition of IV ketamine as a treatment for depression

Close by thanking the FDA for considering your perspective.

‍

Example Provider Comment

I am writing in response to the FDA's call for public comment on drug repurposing for unmet medical needs. I am a licensed psychotherapist who has treated patients with depression for more than 15 years, and I would like to share my clinical experience regarding IV ketamine treatment for depression.

Throughout my career, I have worked with many individuals suffering from severe and treatment-resistant depression. While psychotherapy and conventional psychiatric medications help many patients, a significant subset continue to experience debilitating symptoms despite years of treatment. These patients often struggle to maintain employment, relationships, and daily functioning, and some experience chronic suicidal ideation.

Over the past several years, I have referred a number of patients for IV ketamine treatment when traditional approaches failed to provide adequate relief. Many of these individuals had previously tried multiple antidepressants, psychotherapy, and other interventions without achieving meaningful improvement.

The outcomes I have observed have been remarkable. Patients who had been depressed for years reported substantial reductions in symptoms, increased engagement in therapy, improved relationships, and renewed participation in work and family life. In several cases, improvements occurred after other evidence-based interventions had been exhausted.

I have also observed that IV ketamine treatment is delivered within a highly structured medical setting with appropriate clinical monitoring and coordination between providers. My experience working alongside ketamine treatment providers has reinforced my confidence in the safety and professionalism of this model of care.

Despite these benefits, many of my patients face significant financial barriers to treatment because IV ketamine remains an off-label intervention for depression. Some have delayed treatment, reduced the frequency of recommended maintenance care, or discontinued treatment altogether due to cost.

Based on my clinical experience, IV ketamine addresses a significant unmet need for patients with treatment-resistant depression. An FDA-approved indication for depression could help expand access to a treatment that has provided meaningful benefit to many patients who did not respond to conventional therapies.

Thank you for considering my perspective and experience.

Suggested Structure for Family / Loved One Comments

→ See here for detailed instructions on how to post a comment.

1. Introduce yourself

Describe:

• Your relationship to the patient
• Why you are submitting a comment

2. Your loved one's experience with depression

Describe:

• How depression affected their daily life
• Previous treatments they tried
• The impact on school, relationships, family life, and overall functioning

3. Why your family pursued IV ketamine treatment

Describe:

• What led you to consider treatment
• What other options had been exhausted
• Any concerns you had before beginning treatment

4. Changes you observed

Describe:

• Improvements in mood and functioning
• Changes in motivation, relationships, and quality of life
• Return to activities that had previously become difficult or impossible

Specific examples are especially valuable.

5. The impact on your family

Describe:

• Changes in family life
• Reduced stress or fear
• Renewed hope for your loved one's future

6. Access and affordability

Describe:

• Financial challenges associated with treatment
• Difficulties obtaining insurance coverage
• Why expanded access would matter for families like yours

7. Why FDA recognition would matter

Describe:

• Why you believe IV ketamine addresses an unmet need
• Why other families should have access to this treatment option
• The difference this treatment has made in your loved one's life

‍

Example Family / Loved One Comment

I am writing in response to the FDA's call for public comment on drug repurposing for unmet medical needs. I am the parent of a teenager who received IV ketamine treatment for depression, and I would like to share our family's experience.

For several years, I watched my child struggle with severe depression. We pursued every treatment recommended to us, including psychotherapy, psychiatric care, and multiple antidepressant medications. Despite these efforts, my child continued to experience significant symptoms that affected nearly every aspect of life.

Depression made it difficult for my child to attend school consistently, maintain friendships, participate in activities, and engage with our family. There were periods when we were deeply concerned about their future and whether they would be able to complete high school.

After exhausting many conventional treatment options, we decided to pursue IV ketamine treatment under medical supervision. While we were initially cautious, we felt we had reached a point where we needed to consider additional options.

The changes we observed were remarkable. Over time, my child's mood improved significantly, and they became more engaged with school, family, and friends. They regained motivation, participated more fully in daily life, and began planning for the future again.

Most importantly, IV ketamine treatment helped my child return to school consistently and successfully complete high school. As a parent, seeing them regain the ability to learn, socialize, and move toward adulthood was life-changing for our entire family.

Throughout treatment, we observed a high level of medical oversight and professionalism. We felt confident that our child was receiving safe, carefully monitored care.

Despite the benefits, ongoing treatment has created a significant financial burden for our family because IV ketamine remains an off-label treatment for depression and is not consistently covered by insurance. Access to this care should not depend on a family's ability to pay out of pocket.

Based on our experience, IV ketamine provided meaningful relief when other treatments had failed. An FDA-approved indication for depression could help more families access a treatment that has had a profound impact on our child's health, future, and quality of life.

Thank you for considering our family's experience.

Reference - from the FDA Federal Register

FDA seeks public input from patient, clinical, public health, and research communities on priority disease areas and potential candidates for drug repurposing. In this Federal Register Notice, we are focusing on FDA-approved drugs for which there currently appears to be no commercial interest in adding a new use through a supplemental application. Additionally, we are focusing on such drugs that meet the following criteria for a new use: (1) There is compelling scientific evidence to support the effectiveness of the drug for the new use, (2) the dosage form(s) and route(s) of administration for the new use are the same as for an approved indication, and (3) there is a comparable safety profile for the patient populations for the new use and approved indications. FDA is also seeking input on potential candidates for drug repurposing that may not meet all of the above criteria but have preliminary promising data that might address an unmet need. In particular, FDA seeks comments, data (including real-world data), and information on the following topics:

A second piece of legislation, signed into law as section 324 of the Consolidated Appropriations Act of 2021 (Public Law 116-260), “Modernizing the labeling of certain generic drugs” (commonly referred to as MODERN), added section 503D to the FD&C Act (21 U.S.C. 353d). This legislation established a process through which FDA can require certain updates to the labeling of generic drugs when, among other things, approval of the application for the generic drug's reference listed drug (RLD) has been withdrawn for reasons other than safety or effectiveness, and when there are no unexpired patents or exclusivities listed in the FDA publication “Approved Drug Products With Therapeutic Equivalence Evaluations” (commonly referred to as the Orange Book) for the RLD. Under MODERN, FDA can initiate a process for labeling changes if, among other things, updating the approved labeling would benefit the public health and: “(I) there is new scientific evidence available pertaining to new or existing conditions of use that is not reflected in the approved labeling; (II) the approved labeling does not reflect current legal and regulatory requirements for content or format; or (III) there is a relevant accepted use in clinical practice that is not reflected in the approved labeling.” ^[6]

‍