Approximately one-third of the 21 million Americans diagnosed with major depressive disorder will not achieve remission after trying two or more antidepressant medications — a clinical threshold that defines what psychiatrists call treatment-resistant depression, or TRD. This is not a failure of willpower, and it is not a signal that recovery is impossible. It is a biological reality that some forms of depression involve neurochemical and structural factors that the serotonin and norepinephrine pathways targeted by conventional antidepressants do not adequately address. At Nova Health Recovery in Alexandria, Virginia, we specialize in evaluating and treating patients who have reached this point in their care journey.
Understanding Why Antidepressants Fail
Understanding why antidepressants fail a significant proportion of patients requires stepping back from the popular but incomplete picture of depression as simply “low serotonin.” The monoamine hypothesis — the idea that depression is caused primarily by deficiencies in serotonin, norepinephrine, or dopamine — has been the dominant framework for antidepressant drug development since the 1960s. It produced medications that genuinely help many people. But for patients whose depression is driven more by glutamate system dysregulation, inflammatory processes, disrupted neuroplasticity, or structural changes in the prefrontal cortex and hippocampus, SSRIs and SNRIs may produce little to no relief.
This is the population we are most equipped to serve at Nova Health Recovery. Dr. Christopher Sendi, our board-certified psychiatrist with over 25 years of experience in depression therapies, has worked extensively with patients who arrived at our practice having tried multiple antidepressants, often in combination with psychotherapy, and found that the treatments helped only partially or not at all. The clinical frustration this produces is real, and we take it seriously.
IV ketamine works through the glutamate system. When administered at a sub-anesthetic dose, ketamine blocks NMDA receptors and triggers a rapid release of glutamate, which in turn stimulates AMPA receptors and promotes BDNF production — brain-derived neurotrophic factor, a protein that supports neuronal health and the formation of new synaptic connections. This cascade is thought to restore function in the prefrontal circuits that depression has disrupted, often within hours or days rather than the weeks required by conventional antidepressants. Research into how ketamine for depression works has shown meaningful response rates in the 50 to 70 percent range in patients who failed multiple prior treatments.
We also offer at-home ketamine oral lozenges and ketamine nasal spray for patients whose clinical presentation or logistical circumstances make them better suited to a home-based protocol. For patients with depression who also experience significant anxiety or have difficulty accessing an office setting, this flexibility matters. Our telemedicine follow-up infrastructure, and Dr. Sendi’s availability outside standard business hours, are designed to make ongoing care as accessible as possible.
A barrier we address regularly is the question of what happens after the initial infusion series. Ketamine’s acute effects on depression are powerful but not permanent — the neuroplastic window it opens does not last indefinitely. How patients use that window matters. We work with patients to think about what other therapeutic supports — psychotherapy, lifestyle factors, medication adjustments — might help extend and consolidate the gains from ketamine treatment. Some patients benefit from periodic maintenance infusions. Others find that the initial series produces a durable shift. Results vary by individual, and we plan accordingly.
The second barrier is the concern about seeking care at a standalone ketamine clinic rather than with a psychiatrist who knows one’s full history. This concern is valid, and we welcome it. Dr. Sendi is a board-certified psychiatrist, not simply a ketamine provider. He conducts thorough psychiatric evaluations, reviews medication histories, and works collaboratively with referring and primary care providers. We are a medical practice, not an infusion service, and that distinction matters for outcomes and safety.
We also offer IV NAD+ therapy and IV vitamin therapy, which some patients with depression find complementary. We are transparent about the evidence base for these services and do not present them as primary treatments for TRD. They are supportive wellness interventions that may be appropriate for certain patients as part of a broader plan.
Frequently Asked Questions
What qualifies as treatment-resistant depression?
Most clinical definitions require that a patient has failed to achieve adequate response to at least two antidepressant medications at therapeutic doses for an adequate duration (typically at least six weeks each). Some definitions are more stringent. Dr. Sendi will evaluate your full treatment history during the intake process.
How quickly does IV ketamine work for treatment-resistant depression?
Many patients with TRD report meaningful mood improvement within 24 to 72 hours of their first infusion. The full therapeutic effect of a standard series typically emerges over two to three weeks. Results vary by individual.
Is IV ketamine FDA-approved for depression?
No. IV ketamine is used off-label for depression — its FDA approval is for anesthetic use. The nasal spray form of esketamine (SPRAVATO®) is FDA-approved for TRD and for MDD with acute suicidal ideation, but it is a distinct drug from IV ketamine.
What is the difference between IV ketamine and SPRAVATO® for TRD?
SPRAVATO® is an FDA-approved esketamine nasal spray specifically indicated for TRD and MDD with acute suicidal ideation or behavior. IV ketamine is an off-label treatment. Both are available at Nova Health Recovery. Dr. Sendi will help determine which option is more appropriate given your clinical history and insurance coverage.
How long do the antidepressant effects of IV ketamine last?
Duration varies considerably. Some patients experience sustained improvement for weeks to months following a single infusion series; others benefit from periodic maintenance sessions. We discuss long-term planning openly and adjust the approach based on your individual response.
Key Takeaways
- Treatment-resistant depression affects approximately one-third of MDD patients; it reflects a biological reality, not a personal failing.
- Ketamine acts through the glutamate system, addressing neurobiological drivers of TRD that SSRIs and SNRIs do not adequately target.
- Nova Health Recovery offers IV ketamine, at-home oral ketamine, ketamine nasal spray, and SPRAVATO® for TRD, overseen by Dr. Christopher Sendi, a board-certified psychiatrist.
- Results vary by individual; combining ketamine with ongoing psychotherapy and lifestyle support may improve durability of benefit.
- Discuss with your provider whether IV ketamine or another ketamine modality is appropriate given your specific treatment history.
Conclusion
Treatment-resistant depression is not the end of the road — it is the point at which a different road may need to be found. At Nova Health Recovery, we have built our practice around the patients most conventional psychiatry has not yet been able to help, and we bring to that work a combination of clinical depth, pharmacological breadth, and a genuine commitment to treating each patient as an individual rather than a diagnosis. If you are in Northern Virginia and living with depression that has not responded to conventional treatment, we encourage you to contact us to schedule a consultation and explore your options with a provider who can offer a meaningful, evidence-based evaluation.
About Dr. Christopher Sendi
Dr. Christopher Sendi, MD is a board-certified psychiatrist with over 25 years of experience in addiction treatment, depression therapies, and IV ketamine for pain and mood disorders. He is board certified in addiction medicine, obesity medicine, internal medicine, emergency medicine, and pain management. Dr. Sendi graduated from Georgetown University Medical School (MD, 1992) and has special interests in the application of ketamine infusions for the treatment of depression, PTSD, anxiety, pain, CRPS, Lyme disease, and neuropathies. He leads Nova Health Recovery in Alexandria, Virginia, offering IV ketamine, ketamine-assisted psychotherapy (KAP), at-home oral ketamine lozenges, ketamine nasal spray, and Spravato, as well as IV NAD+, IV vitamin therapy, and integrated addiction medicine services. Dr. Sendi provides telemedicine follow-up and is available outside standard business hours to accommodate patients’ schedules.
References
National Institute of Mental Health, Major Depression — https://www.nimh.nih.gov/health/statistics/major-depression
American Psychiatric Association, Treatment-Resistant Depression — https://www.psychiatry.org/patients-families/depression/what-is-depression
Journal of the American Medical Association (JAMA Psychiatry), Ketamine for Treatment-Resistant Depression — https://jamanetwork.com/journals/jamapsychiatry
U.S. Food and Drug Administration, SPRAVATO® Prescribing Information — https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/211243s004lbl.pdf
Medical Disclaimer
The information in this article is provided for educational purposes only and does not constitute medical advice. Ketamine therapies at Nova Health Recovery are supervised by a licensed physician; however, individual results vary and this content should not be interpreted as a guarantee of any outcome. IV ketamine for depression is off-label. Please consult a qualified healthcare provider to determine whether ketamine therapy is appropriate for your specific circumstances.