Treatment-Resistant Depression: When Antidepressants Stop Working, There Is Another Way
Treatment-resistant depression (TRD) is what doctors call it when major depression doesn’t respond to at least two different antidepressant medications taken at the right doses for a long enough time. If that describes your experience, years of trying medications that either stopped working or never really worked, you are not alone, and you have not run out of options. NeuroGlow specializes in exactly this.
Trusted by 1000+ Patients
Medically reviewed by Dr. Aaron Brown, DO, Medical Director and Board-Certified Psychiatrist · Last reviewed July 2026 · Updated July 12, 2026
What Is Treatment-Resistant Depression?
The clinical definition: major depressive disorder (MDD) that fails to respond to at least two different antidepressants from different drug classes, taken at adequate doses for at least 4–6 weeks each. Many patients with TRD have tried five, ten, or more medications over years or decades. TRD is not a personal failure. It is a biological variant of depression that requires a different class of treatment entirely.
How Do You Know If You Have TRD?
You may have TRD if:
- You have been diagnosed with major depressive disorder.
- You have tried at least two antidepressants at therapeutic doses for adequate durations.
- Your depression has not achieved remission.
- You continue to experience significant symptoms despite medication.
You don’t need a formal TRD label from a previous provider. Our board-certified psychiatrist will review your history and make the determination. Many patients who have been told ‘you just need to find the right medication’ have unrecognised TRD.
Why Do Some People Not Respond to Antidepressants?
Standard antidepressants target serotonin and norepinephrine. For many patients with TRD, these neurotransmitter systems are not the primary driver of their illness. Their depression involves dysregulation of the glutamate system (specifically NMDA receptors), which no oral antidepressant addresses. This biological difference explains why medications can be taken correctly and still not work. It has nothing to do with compliance or attitude.
Spravato for TRD
In 2019, the FDA approved Spravato (esketamine) as the first new class of antidepressant in over 30 years specifically for treatment-resistant depression. Unlike traditional antidepressants that target serotonin, Spravato works on NMDA glutamate receptors, producing rapid antidepressant effects within hours or days rather than weeks. Because it is FDA-approved for TRD, most major insurance plans cover it. NeuroGlow is a certified Spravato treatment center in DFW.
IV Ketamine for TRD
IV ketamine infusions have been used for treatment-resistant depression since the early 2000s and remain the most studied rapid-acting antidepressant in psychiatry. While not FDA-approved specifically for depression (making it an off-label treatment), the clinical evidence is exceptionally strong, with response rates of 50–70% in TRD populations who have failed multiple prior treatments. IV ketamine is available at NeuroGlow as a self-pay treatment with the six-infusion induction series priced at $3,500.
How We Choose Between Spravato and IV Ketamine
Both medications work on the same glutamate system, but the right choice depends on your insurance, your history, and your logistics. Spravato is the on-label, FDA-approved option for treatment-resistant depression, and because it is covered by most commercial plans as well as Medicare, Medicaid, and TriWest, it is usually the first choice for insured patients. IV ketamine offers precise, weight-based dosing that can be adjusted infusion by infusion, which some patients and prescribers prefer, particularly when there is a history of partial response or when appointment flexibility matters. During your consultation, Dr. Brown reviews your medication history, diagnosis, and coverage, and recommends a starting path. Choosing one does not close the door on the other; patients sometimes transition between them based on response.
TMS: An Option Some Patients Consider
Some patients exploring treatment for treatment-resistant depression also consider transcranial magnetic stimulation (TMS), an FDA-cleared, non-medication treatment that uses magnetic pulses to stimulate the brain regions involved in mood regulation. TMS requires no anesthesia or recovery time and is covered by most insurance plans for treatment-resistant depression. NeuroGlow does not currently offer TMS, but it can be a reasonable option for patients who prefer to avoid medication or who have not responded to ketamine-based treatment. During your consultation we are glad to talk through how TMS compares to Spravato and IV ketamine so you can make an informed choice.
The Research Behind Ketamine and Esketamine for TRD
This is not experimental territory. Ketamine’s rapid antidepressant effect was first demonstrated in a controlled trial by Berman and colleagues in 2000 (Biological Psychiatry) and replicated at the National Institute of Mental Health by Zarate in 2006 (Archives of General Psychiatry), where patients with treatment-resistant depression improved within hours of a single infusion. Murrough’s 2013 trial established the six-infusion induction protocol that remains the standard of care, and Wilkinson’s 2018 meta-analysis confirmed the effect across pooled controlled trials. Spravato’s FDA approval rests on the TRANSFORM trial program, with SUSTAIN-1 showing that continued maintenance dosing significantly reduces relapse, and the ASPIRE trials supporting its approval for depressive symptoms in adults with acute suicidal ideation or behavior. When we recommend these treatments for TRD, this is the evidence base behind the recommendation.
How NeuroGlow Treats TRD Differently
We track every patient’s outcomes using the PHQ-9, a validated clinical scale. We don’t guess at improvement. We measure it. Our board-certified psychiatrist personally reviews every case. You receive individualised treatment recommendations, not a standardised protocol. Our care coordinators manage insurance verification, prior authorisation, and scheduling from start to finish. All three clinics offer private treatment rooms.
TRD and Suicidal Ideation
Severe TRD carries an elevated risk of suicidal ideation. If you or someone you know is experiencing thoughts of suicide, call 988 (Suicide & Crisis Lifeline) or go to the nearest emergency room immediately. Spravato is also FDA-approved for MDD with acute suicidal ideation, and it can begin working within hours for patients in acute crisis. That fast-acting effect is one of the reasons it has become such an important option in urgent depressive episodes.
NeuroGlow offers urgent consultation appointments. If the situation is urgent but not immediately life-threatening, call 469-218-4410 so our team can help you understand the fastest next step.
Our TRD Patient Outcomes
We track every patient’s depression severity using the PHQ-9. Our clinic data shows an average improvement of 8+ points after a full treatment course. An 8-point drop typically means the difference between moderate-severe depression and mild depression. We publish our outcomes because we believe transparency builds trust.
TRD Care Across Dallas-Fort Worth
NeuroGlow treats treatment-resistant depression at three clinics across the DFW Metroplex: our flagship in Flower Mound, our McKinney clinic with evening and Saturday hours, and our Fort Worth clinic on North Tarrant Parkway. Patients come to us from Dallas, Plano, Frisco, Arlington, Denton, and communities across North Texas, and all three locations are REMS-certified for Spravato. If you have been cycling through antidepressants with a Dallas-area provider, we are happy to coordinate care with them; many of our patients continue seeing their existing psychiatrist or therapist while receiving interventional treatment here. One number reaches all three clinics: +1 469-218-4410.
What the First Step Looks Like
It starts with a free phone or video consultation with our care coordinator. No commitment, no pressure. We’ll listen to your history, explain your options, and verify your insurance coverage for Spravato. If IV ketamine is more appropriate, we’ll walk through pricing and the treatment schedule. You’ll leave the call knowing exactly what your path to treatment looks like and what it will cost.
Treatment-Resistant Depression FAQs
What qualifies as treatment-resistant depression?
Depression is generally considered treatment resistant when symptoms have not improved after at least two different antidepressants, taken at an adequate dose for an adequate length of time. Roughly one in three people treated for major depression fall into this category. A formal evaluation also rules out other contributors such as thyroid conditions, bipolar disorder, or substance use.
What treatments does NeuroGlow offer for treatment-resistant depression?
NeuroGlow offers Spravato (esketamine), an FDA-approved nasal spray for treatment-resistant depression, and IV ketamine infusion therapy used off-label for TRD. Care is directed by Dr. Aaron Brown, DO, a board-certified psychiatrist, and treatment plans are matched to your history, insurance, and goals.
Does insurance cover treatment for treatment-resistant depression?
Spravato is covered by most commercial insurance plans as well as Medicare, Medicaid, and TriWest, and eligible commercially insured patients may qualify for the SPRAVATO withMe savings program with copays as low as $10 per treatment. IV ketamine is self-pay at $3,500 for a six-infusion induction series, with CareCredit and HSA/FSA accepted. We verify your benefits before your first visit.
How quickly do these treatments work?
Unlike oral antidepressants, which typically take four to six weeks to take effect, ketamine and esketamine can begin relieving symptoms within hours to days. In the TRANSFORM-2 clinical trial, Spravato plus an oral antidepressant produced significantly greater improvement than placebo at 28 days, with some patients responding within the first week.
Is ketamine treatment safe for treatment-resistant depression?
Both treatments are administered in clinic under medical supervision. Spravato is given only at REMS-certified clinics, and all three NeuroGlow locations are certified, with a monitored observation period after each dose. Side effects such as dissociation, dizziness, or elevated blood pressure are typically mild and resolve before you leave the clinic. You will need a ride home after each session.
If depression hasn’t improved after multiple medications, you may be dealing with treatment-resistant depression. Our team can review your history, explain Spravato and IV Ketamine, and help you understand the next step.