If you have been taking antidepressants for months (or years) without meaningful relief, you are not alone, and it is not your fault. Roughly one in three adults with depression does not respond adequately to two or more standard antidepressant trials, a condition clinicians call treatment-resistant depression, or TRD. For those people, ketamine therapy has become one of the most evidence-supported alternatives available in Manhattan.
This guide covers what the research says about ketamine for TRD, the criteria that separate a safe and effective clinic from a mediocre one, and what Nushama offers members who are ready to explore a different path.
A quick note on timing: In April 2026, President Trump signed an executive order directing the FDA to fast-track review of psychedelic therapies and committing $50 million in federal research funding. While ketamine is already legal and widely available, this order signals growing federal support for the broader field of psychedelic-assisted mental health care, and it may expand insurance pathways in the years ahead.
Why ketamine can help when antidepressants have not
Standard antidepressants (SSRIs, SNRIs, tricyclics) target serotonin and norepinephrine systems. They work for many people, but not everyone. Ketamine operates through a different mechanism: it acts on the NMDA glutamate receptor, which triggers a cascade of changes that can promote neuroplasticity, the brain’s ability to form new neural pathways.
The practical difference for people with TRD is speed and response rate. According to a 2025 systematic review published in the Global Journal of Medicine and Public Health, up to 70% of people with treatment-resistant depression may respond to ketamine, with effects appearing as early as four hours after the first infusion and peaking at 24 hours. That same review found that repeated infusions had cumulative effects, with 59% of participants meeting response criteria after an average of three sessions.
A 2025 study in the Journal of Clinical Psychiatry (Meisner et al.) compared IV ketamine to intranasal esketamine (Spravato) in a naturalistic clinical setting and found that IV ketamine was associated with faster response and greater overall efficacy during a four-to-five-week treatment period.
For those dealing with PTSD alongside depression, a 2024 study published in the Journal of Psychopharmacology by Henry A. MacConnel, Mitch Earleywine, and Steven Radowitz, titled “Rapid and sustained reduction of treatment-resistant PTSD symptoms after intravenous ketamine in a real-world, psychedelic paradigm,” found that 75% of 117 participants with treatment-resistant PTSD experienced clinically meaningful improvement, and 62% reached remission. The study highlighted the role of preparation, integration, and sensory immersion in these outcomes.
None of this means ketamine is a cure. Effects from a single infusion may be short-lived, and most protocols involve a series of treatments with periodic boosters. The evidence supports ketamine as a catalyst for change, especially when paired with therapeutic support.
Five criteria for evaluating a ketamine clinic in Manhattan
Not all ketamine providers offer the same level of care. The number of clinics in New York City has grown quickly, and quality varies. Here are the criteria that matter most when choosing a provider.
1. Medical expertise and in-session oversight
A qualified clinic employs board-certified physicians or psychiatric specialists who conduct thorough medical assessments before treatment. During infusions, a physician or registered nurse should monitor your vitals, adjust dosing in real time, and manage any side effects. Clinics that offer same-day appointments without screening, or that leave you unmonitored during treatment, are red flags.
2. Preparation and integration support
Ketamine is not a pill you take and forget. The sessions themselves can bring up intense emotions, memories, and altered states of awareness. Preparation (setting intentions, understanding what to expect) and integration (processing the experience afterward with a licensed therapist or trained coach) are what help initial relief turn into lasting change. Ask whether the clinic includes these services or expects you to arrange them on your own.
3. Treatment environment
Research, including the MacConnel et al. (2024) PTSD study referenced above, suggests that the setting in which ketamine is administered affects outcomes. Look for private treatment spaces, calming design, ambient music or sound options, and an overall atmosphere that feels safe rather than clinical or transactional.
4. Personalized protocols
Depression is not one-size-fits-all, and ketamine treatment should not be either. The best clinics adjust dosing, session frequency, and treatment duration based on your diagnosis, symptom severity, medication history, and individual response. A standard protocol might involve six infusions over three to six weeks, but your plan should be tailored to you.
5. Transparency about IV vs. other delivery methods
IV (intravenous) ketamine offers the most precise dosing control because it enters the bloodstream directly, allowing clinicians to adjust the rate of infusion in real time. Other delivery methods, such as intranasal sprays, lozenges, or at-home tablets, can be less predictable in terms of absorption and onset. Esketamine (brand name Spravato) is the only FDA-approved nasal spray for TRD, but as the 2025 Meisner et al. study noted, IV ketamine showed faster and greater response in direct comparison. A trustworthy clinic will explain the differences and recommend the route that fits your clinical picture.
How Nushama approaches treatment-resistant depression
At Nushama, we designed our care model around the understanding that medicine alone is not enough. Here is how the process works for people exploring ketamine therapy with us in Manhattan.
Consultation and medical assessment. Every member begins with a psychiatric intake that reviews your full treatment history, current medications, and health status. Pre-treatment testing may include blood work, urine screening, blood pressure monitoring, and an EKG. This step confirms that ketamine is appropriate and safe for you.
Preparation. Before your first session, our team helps you set intentions and prepare your mindset for the experience ahead. This matters because ketamine therapy is unlike most other treatments you have encountered. Preparation helps you approach the session with clarity rather than anxiety.
IV ketamine sessions. Nushama physicians typically administer six infusions over a three-to-six-week period, with up to two infusions per week. Sessions take place in a serene environment with therapeutic artwork, ambient music, and comfortable zero-gravity chairs. Your vitals and anesthesia levels are continuously monitored by physicians and nurses throughout.
Integration. After each session, licensed therapists or trained integration coaches help you process insights and incorporate what you have experienced into your daily life. This is where initial symptom relief can become durable change.
Community and ongoing support. Nushama also offers group programming and community events because healing often happens more fully in connection with others.
We choose IV ketamine as our primary method because it provides the safest and most efficacious delivery, according to current evidence. While we also offer Spravato (esketamine) for members who may benefit from that route, our physicians will discuss which option best fits your needs.
The federal executive order: what it means for ketamine therapy
On April 18, 2026, President Trump signed an executive order directing federal agencies to accelerate research and access to psychedelic therapies for serious mental illness. According to NPR, the order instructs the FDA to expedite its review of drugs like ibogaine and psilocybin, directs $50 million through the Advanced Research Projects for Health (ARPA-H) program to match state government investments in psychedelic research, and ordered the FDA to fast-track a review process that could lead to approval in weeks rather than years.
As CNN reported, the FDA followed by issuing National Priority Vouchers to psychedelic compounds with Breakthrough Therapy designation, which could shorten approval timelines.
Legal experts at Harvard’s Petrie-Flom Center have noted that the practical effects will take time to unfold and depend on how individual agencies implement the order. The executive order also expands access through the Right to Try Act, which may eventually broaden eligibility for patients with serious mental illness.
What does this mean for ketamine specifically? Ketamine is already legal, widely available, and does not need rescheduling. But the order’s broader push toward psychedelic-assisted therapy could drive more research funding, more insurance coverage conversations, and more public acceptance of treatments like ketamine. For anyone considering ketamine therapy now, the regulatory direction is encouraging.
Making the decision: what to consider before starting
Starting ketamine therapy is a personal decision that benefits from honest conversation with a clinician who understands your full picture. Here are a few things worth considering:
- Your treatment history. Ketamine therapy is typically explored after at least two antidepressant trials have not provided adequate relief. Bring a clear record of what you have tried and how you responded.
- Your support system. Someone who can drive you home after sessions and check in during your treatment course makes a difference. Integration is also easier when the people around you understand what you are doing and why.
- Cost and coverage. IV ketamine is generally not covered by insurance. Spravato (esketamine) often has insurance pathways for people who meet TRD criteria. Ask any clinic you are considering about pricing, payment plans, and insurance coordination up front.
- Contraindications. Ketamine may not be appropriate for people with certain conditions, including uncontrolled hypertension, active psychosis, or specific cardiac concerns. A thorough medical screening will identify any issues before treatment begins.
If you are ready to explore whether ketamine therapy is right for you, book a consultation with our care team to discuss your history and next steps.
FAQs
How quickly does ketamine work for treatment-resistant depression?
- Many people notice changes within hours of their first IV infusion. According to a 2025 systematic review in the Global Journal of Medicine and Public Health, effects can appear as early as four hours after infusion and peak at 24 hours. The full benefit of a treatment series typically becomes clearer after three to six sessions.
Is ketamine therapy safe?
- When administered intravenously in a medically supervised clinic with proper screening, ketamine therapy has a well-documented safety profile. Common side effects include mild dissociation (a temporary feeling of detachment), dizziness, and nausea. These typically resolve within an hour of the session ending. Serious adverse events are rare in properly supervised settings.
What is the difference between ketamine and Spravato?
- IV ketamine uses racemic ketamine (both the R and S forms of the molecule) delivered directly into the bloodstream for precise dosing. Spravato is an FDA-approved nasal spray containing only esketamine (the S form). A 2025 study in the Journal of Clinical Psychiatry found that IV ketamine was associated with faster response and greater efficacy than intranasal esketamine over a four-to-five-week treatment period.
Does insurance cover ketamine therapy?
- IV ketamine is generally not covered by insurance. Spravato (esketamine) is more likely to be covered for people who meet criteria for treatment-resistant depression, though prior authorization is usually required. At Nushama, our team can help you understand your coverage options and navigate the insurance process.
What should I expect during a ketamine session?
- Sessions typically last about 40 to 60 minutes for the infusion itself, with additional time for preparation and recovery. You may experience visual changes, a feeling of deep relaxation, or a sense of separation from your usual way of thinking. A medical professional monitors you throughout. Most people feel well enough to leave the clinic about 30 to 60 minutes after the infusion ends, though you will need someone to accompany you home.
How do I know if I am a good candidate for ketamine therapy?
- Ketamine therapy may be appropriate if you have been diagnosed with depression, anxiety, PTSD, OCD, or another qualifying condition, and have not responded well to standard treatments. The best way to find out is to speak with our care team about your history and goals. A medical consultation will determine whether ketamine is a safe and appropriate option for you.
