Nearly one-third of people diagnosed with major depressive disorder do not respond adequately to two or more antidepressant medications — a clinical pattern now recognized as treatment-resistant depression (TRD). Despite years of medication trials, therapy, and lifestyle adjustments, millions of South Floridians live with persistent depression that simply does not lift. At One Mind in Fort Lauderdale, we work with patients who have reached that point and are searching for a medically supervised path forward.
What Treatment-Resistant Depression Actually Means
Treatment-resistant depression is not a character flaw or a sign that recovery is impossible. Clinically, it describes a pattern in which major depressive disorder persists after at least two adequate trials of antidepressant therapy at therapeutic doses for sufficient duration. The condition affects an estimated 3.7 million Americans and carries a disproportionately high burden of disability, impaired work functioning, and reduced quality of life. Understanding that TRD is a recognized clinical entity — not simply “hard-to-treat sadness” — is the first step toward exploring options that go beyond the standard medication ladder.
At One Mind, we begin every evaluation by reviewing a patient’s full psychiatric and medical history. Before any treatment decision is made, our team ensures we understand exactly which medications have been tried, at what doses, and for how long. That kind of thorough intake is how we build treatment plans that are genuinely personalized rather than generic. Learn more about our approach on our Depression Treatment in Fort Lauderdale, FL page.
How IV Ketamine Works Differently
Conventional antidepressants — SSRIs, SNRIs, TCAs — primarily target monoamine neurotransmitters like serotonin, norepinephrine, and dopamine. They typically require four to six weeks before any meaningful effect appears, and a large proportion of patients cycle through multiple agents without finding one that works. IV ketamine operates through an entirely different mechanism, acting as an NMDA receptor antagonist that affects glutamate signaling, the brain’s primary excitatory neurotransmitter system. Preclinical and clinical research has documented rapid synaptogenesis — the formation of new synaptic connections in cortical regions associated with mood — following ketamine infusions.
It is important to note that ketamine’s psychiatric applications, including its use for treatment-resistant depression, are off-label uses of the drug. The FDA has not approved IV ketamine for depression specifically. What the research does consistently show is a rapid onset of antidepressant effects in patients who have not responded to other treatments — effects that often appear within hours to days after the first infusion. Results vary by individual, and no single treatment is effective for every patient. Discuss with your provider whether IV ketamine therapy is appropriate for your specific clinical situation.
Our Six-Infusion Protocol
Our standard protocol at One Mind delivers a series of six IV ketamine infusions administered over two to three weeks. Each infusion is physician-supervised, with careful monitoring of vital signs, sedation level, and patient comfort throughout the session. We conduct each infusion in a calm, intentionally comfortable setting — not a sterile procedural room — because the environment during treatment matters for patient experience.
The turquoise waters and warm Atlantic light of Fort Lauderdale are never far from mind when we think about what healing can look like in South Florida. We want our patients to feel that the space they enter for treatment reflects the calm and openness of the natural world they live in, not the fluorescent anxiety of a waiting room.
Between infusions, we encourage patients to maintain close contact with their existing therapists or psychiatric providers. IV ketamine is not a standalone intervention — it is most effective when the neurological window it opens is met with intentional therapeutic work. We coordinate directly with trauma-focused care providers and therapists to ensure that integration is built into the process from the start. Our Preparation & Integration Coaching program is designed to support exactly that kind of intentional follow-through.
Addressing the Cost Barrier
One of the most common questions we receive is about cost. IV ketamine therapy is not typically covered by commercial insurance for psychiatric indications, and the out-of-pocket investment for a six-infusion series is a real consideration for most patients. We are transparent about fees during the initial consultation so that financial planning is part of the conversation from the beginning, not an afterthought after a patient has already committed emotionally to pursuing treatment. For a detailed breakdown, visit our Ketamine Therapy Cost & Insurance page.
We encourage patients to ask about payment options, and we work with families to think through the practical side of access. We never want cost alone to be the reason someone does not explore a treatment that may meaningfully improve their quality of life.
What to Expect During Infusions
Each infusion session lasts approximately 40 to 60 minutes. Patients recline comfortably while the ketamine is delivered intravenously at a carefully calibrated dose. Most patients report a dissociative or dream-like experience during the infusion — perceptual shifts, altered sense of time, or a floating sensation. These effects are temporary and resolve within a short time after the infusion ends. A responsible adult must accompany each patient home afterward, as driving or operating machinery is not safe for the remainder of the day.
Many patients describe the experience as unusual but not unpleasant, and some find it meaningful in ways they did not anticipate. Our team remains present throughout every infusion to answer questions, monitor your well-being, and ensure the session is as comfortable as possible. For a full walkthrough of the process, see First Ketamine Infusion in South Florida.
FAQ
What qualifies as treatment-resistant depression?
Treatment-resistant depression (TRD) is generally defined as major depressive disorder that has not adequately responded to at least two antidepressant trials of adequate dose and duration. Your prescribing provider can review your medication history to help determine whether TRD applies to your situation.
How quickly might I notice a difference after IV ketamine?
Some patients report mood improvements within 24 to 72 hours after their first infusion. Others notice gradual improvement over the course of the full series. Response timelines vary considerably from person to person, and results vary by individual. Discuss realistic expectations with your provider before beginning treatment.
Is IV ketamine safe?
IV ketamine has been used in clinical and surgical settings for decades and has a well-established safety profile when administered in supervised medical settings. At One Mind, every infusion is physician-supervised, with monitoring for vital signs and patient comfort throughout. As with any medical treatment, potential risks and contraindications should be reviewed with your provider.
How long do the effects of ketamine last?
The duration of benefit after a ketamine series varies. Some patients experience sustained improvement for months; others require maintenance infusions at longer intervals. Your provider will work with you to establish a follow-up and maintenance plan tailored to your response.
Do I need to stop my current medications before treatment?
Not necessarily, but a thorough medication review is part of our intake process. Certain medications may interact with ketamine or affect the infusion experience. Our team reviews your full medication list before treatment begins and will advise you on any adjustments needed.
Key Takeaways
- Treatment-resistant depression affects roughly one-third of people with major depressive disorder and is a recognized clinical diagnosis, not a personal failing.
- IV ketamine acts on the glutamate system via NMDA receptor antagonism — a mechanism entirely different from conventional antidepressants.
- Ketamine’s use for depression is off-label; patients should discuss the evidence base, risks, and alternatives with their provider.
- One Mind’s six-infusion protocol is physician-supervised and coordinated with existing mental health providers for integrated care.
- Results vary by individual, and outcomes depend on clinical history, response pattern, and ongoing therapeutic engagement.
Conclusion
Treatment-resistant depression is a heavy burden, but it is not the end of the road. IV ketamine therapy offers a clinically distinct mechanism of action that may open a door that conventional medications have not. At One Mind, we approach every patient with the medical rigor and human care that a condition this serious demands. If you or someone you love has been living with depression that hasn’t responded to standard treatments, we encourage you to schedule a consultation and explore whether IV ketamine therapy is the right fit for your situation.
References
American Psychiatric Association. https://www.psychiatry.org
National Institute of Mental Health. https://www.nimh.nih.gov
Murrough JW et al., Antidepressant Efficacy of Ketamine in TRD — American Journal of Psychiatry. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3844503/
Harvard Health Publishing. https://www.health.harvard.edu
Our Team
Dr. Jacob Topfer and Dr. Matt Graca serve as Co-Medical Directors at One Mind Ketamine in Fort Lauderdale. Both are board-certified anesthesiologists and pain management physicians who completed their fellowships at the University of Miami. That clinical background shapes how One Mind approaches every infusion: with the dosing precision, monitoring standards, and real-time adjustment that anesthesia-trained care requires. Each patient’s treatment plan is personalized following a full review of psychiatric and medical history, with a focus on patients who have not found adequate relief through conventional care.
Medical Disclaimer
The content on this page is provided for educational purposes only and does not constitute medical advice, diagnosis, or treatment. IV ketamine therapy is an off-label treatment for psychiatric conditions. Results vary by individual, and not all patients will experience the same outcomes. This information should not be used as a substitute for professional medical advice. Always discuss treatment options, potential risks, and your personal health history with a qualified healthcare provider before making any medical decisions.