---
title: "Treatment-Resistant Depression"
---
## When Antidepressants Haven't Been Enough
If you have tried multiple antidepressants without finding adequate relief, you are not alone, and you have not failed. Approximately one-third of patients with major depression do not achieve adequate response from conventional antidepressants, even after multiple trials. Clinicians describe this as treatment-resistant depression, or TRD. It is a common, recognized clinical situation, not a personal shortcoming.
The standard sequence often goes something like this: an SSRI that helped some, then did not. A different SSRI that helped a little. An SNRI that produced side effects. Augmentation with another medication that did or did not help. Therapy throughout, sometimes helping, sometimes not enough. For patients in this situation, ketamine infusion therapy has emerged as one of the most clinically significant developments in mental health care in decades. It is not a miracle cure, and we will not oversell it, but for the right patient it can produce meaningful improvement when nothing else has.
## What This Page Is and Isn't
PHI is not a psychiatry practice. We do not manage ongoing depression care, prescribe antidepressants, or provide psychotherapy. What we offer is one specific physician-administered medical intervention: ketamine infusion therapy, which has the strongest evidence base in mental health for treatment-resistant depression specifically. We work alongside your psychiatrist and therapist, not in place of them.
## Why Ketamine Works When Other Treatments Haven't
Most antidepressants act on serotonin, norepinephrine, or related neurotransmitter systems. They typically take 4 to 6 weeks to produce noticeable effects, and approximately one-third of patients do not respond adequately to multiple trials.
Ketamine acts through a completely different pathway. It modulates the NMDA receptor and glutamate signaling, which are involved in synaptic connections, neuroplasticity, and the neural networks affected in depression. The effects can develop within hours to days rather than weeks. For patients whose depression has not responded to serotonin-targeted treatments, this different mechanism is the central reason ketamine often works when other treatments have not.
## What the Evidence Shows
Ketamine for treatment-resistant depression has the strongest evidence base in mental health applications. Randomized controlled trials have consistently demonstrated rapid antidepressant effects, with meaningful symptom reduction within 24 to 72 hours sustained by continued treatment. The 2019 FDA approval of esketamine (intranasal, brand name Spravato) for treatment-resistant depression validated the broader finding that NMDA receptor modulation produces antidepressant effects.
IV ketamine, the form PHI provides, has accumulating evidence and is widely used by physicians experienced in its administration. While IV ketamine is used off-label for TRD, its clinical use is supported by a substantial body of research. Effects on suicidal ideation have been documented specifically, with studies showing rapid reductions in suicidal thinking, often within hours, which is meaningfully different from standard antidepressants that take weeks to affect this domain.
## How PHI Approaches Ketamine for TRD
The first step is a comprehensive evaluation: a detailed history of your depression and treatment trials, confirmation of your established diagnosis and current providers, review of medication trials and durations, assessment of medical history and contraindications, and an honest discussion of what ketamine can realistically offer for your situation.
For appropriate candidates, treatment involves physician-administered IV infusions in a clinic setting under continuous monitoring of vital signs. Sessions are performed in our clinic setting, and the time they take varies by patient, dose, and treatment. There is no fixed protocol: the number of sessions and their spacing are tailored to each patient and discussed during consultation rather than following a set series. We coordinate with your mental health team throughout, and for patients who respond well we discuss maintenance individually. You may be a candidate if you have an established major depression diagnosis, ongoing mental health care, an adequate trial of at least two antidepressants without sufficient response, and no contraindications. You are typically not a candidate if you are in active crisis, have specific medical contraindications, or are seeking ketamine without the framework of broader treatment.
## Why PHI for Treatment-Resistant Depression
## Frequently Asked Questions
**Q: How is ketamine for depression different from how it's used in surgery?**
The doses are dramatically different. Surgical anesthesia uses ketamine at high doses to produce unconsciousness. Therapeutic ketamine for depression uses subanesthetic doses, typically about one-tenth of surgical doses, that produce mood-modulating effects without unconsciousness. You remain awake, aware, and able to communicate throughout.
**Q: Is ketamine FDA-approved for depression?**
Esketamine (intranasal, brand name Spravato) is FDA-approved specifically for treatment-resistant depression. IV ketamine, what PHI provides, is used off-label for depression. Off-label use means prescribed based on clinical evidence outside specific FDA approval for that indication, which is common in medicine, particularly for emerging treatments. The clinical evidence for IV ketamine in TRD is substantial.
**Q: How fast does ketamine work?**
Often within hours to days of an early session. Many patients experience meaningful mood improvement within 24 to 72 hours, with benefit building over the course of treatment. This is meaningfully faster than standard antidepressants, which typically require 4 to 6 weeks.
**Q: How long do the effects last?**
This varies. Effects from a single session are typically temporary, which is why treatment is delivered as a tailored course rather than a single dose. After an initial course, some patients experience sustained response for months; others receive periodic maintenance. Your physician will help you understand what your trajectory might look like.
**Q: Will I be unconscious during the infusion?**
No. PHI uses subanesthetic doses that produce dissociative effects, which can include altered perception or a sense of detachment, but not unconsciousness. Most patients describe a mild to moderately altered, dream-like awareness.
**Q: Will I need to stop my antidepressants?**
Generally no. Most patients continue their current medications during ketamine treatment. The goal is typically improved response on the combination rather than replacement. Some patients eventually reduce other medications under their psychiatrist's guidance after sustained response, a careful process managed by your mental health team.
**Q: Will I become addicted?**
Recreational ketamine use carries addiction risk. Medical ketamine in a defined, monitored treatment course with subanesthetic dosing has not been associated with significant addiction risk in clinical use. The setting and protocol matter significantly.
**Q: What about ECT or TMS?**
ECT, TMS, and ketamine each have specific evidence and roles in treatment-resistant depression. ECT has the strongest evidence for severe TRD but requires anesthesia. TMS is non-invasive but typically requires daily sessions over weeks. Ketamine offers rapid effects with a different side effect profile. Your psychiatrist can help you understand which approach might fit best; PHI provides ketamine as one of several options.
**Q: How does this compare to ketamine clinics I see advertised?**
PHI is a physician-led medical practice, not a standalone wellness clinic. Ketamine is administered by our board-certified physicians under continuous monitoring. We require existing mental health care, coordinate with your providers, and use individualized evidence-based treatment. This is meaningfully different from many freestanding ketamine clinics.
**Q: Do you take insurance?**
Insurance coverage and payment options may vary. All pricing is disclosed at consultation.
**Q: Do you accept international patients?**
Yes. PHI regularly treats patients from outside Los Angeles, including Las Vegas, Palm Springs, London, and other international locations. Ketamine treatment can be coordinated to fit travel schedules.
## Treatments We Offer for Treatment-Resistant Depression
PHI offers physician-administered ketamine infusion therapy, the most evidence-supported intervention for depression that has not responded to standard antidepressants. We work alongside your mental health team rather than replacing the broader care you need.
- Ketamine Infusion Therapy, physician-administered in a clinic setting
> Synthesizing the evidence for ketamine and esketamine in treatment-resistant depression: an international expert opinion on the available evidence and implementation. American Journal of Psychiatry.
— [McIntyre RS, et al.](https://pubmed.ncbi.nlm.nih.gov/33726522/)
> Ketamine for rapid reduction of suicidal thoughts in major depression: a midazolam-controlled randomized clinical trial. American Journal of Psychiatry.
— [Grunebaum MF, et al.](https://pubmed.ncbi.nlm.nih.gov/29202655/)
> A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry.
— [Sanacora G, et al.](https://pubmed.ncbi.nlm.nih.gov/28249076/)
> Practice guideline for the treatment of patients with major depressive disorder. American Psychiatric Association.
— [American Psychiatric Association](https://psychiatryonline.org/doi/book/10.1176/appi.books.9780890423387.654001)
## Schedule Your TRD Consultation
A 60-minute consultation will evaluate whether ketamine infusion therapy is appropriate for your specific situation, walk through what to expect, and coordinate with your mental health team. Call (310) 856-9488 or book online now.
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