Treatment-resistant depression can make people feel as though they have run out of options. After several medication trials, therapy, and significant effort to follow a treatment plan, it can be discouraging when depression still affects work, relationships, sleep, motivation, and the ability to function day to day.
At our Bellaire clinic, we work with adults whose depression has not improved adequately with standard treatment. A limited response is not a personal failure, and it does not mean that depression is untreatable. It is a reason to take a closer look at the diagnosis, treatment history, coexisting conditions, and next-step options.
What Treatment-Resistant Depression Means
There is no single definition of treatment-resistant depression used in every clinical setting. In many cases, the term refers to major depressive disorder that has not improved sufficiently after at least two adequate antidepressant trials.
An adequate treatment trial involves more than receiving a prescription. It includes the medication choice, dose, duration, tolerability, adherence, and the degree of symptom improvement. For some patients, a medication may help somewhat but not enough to restore daily functioning. For others, side effects may make it difficult to continue treatment at an effective dose.
When depression has not responded as expected, it is important not to assume that the only next step is another similar medication trial. A more complete review can help clarify whether the diagnosis still fits, whether another psychiatric or medical concern may be contributing, whether psychotherapy has been adequately incorporated, and whether an interventional treatment may be appropriate. Our post on 4 Things We Now Know About Treatment-Resistant Depression offers helpful background on how thinking in this area has evolved.
A Comprehensive Evaluation Comes First
Depression can be complicated by anxiety, trauma-related symptoms, sleep disruption, chronic pain, substance use, medical conditions, medication effects, or bipolar-spectrum symptoms. These concerns do not always rule out treatment-resistant depression, but they can affect how a treatment plan should be structured.
At our clinic, we review the course of depression over time, previous medication trials, prior therapy, current symptoms, medical history, sleep, and the practical impact depression is having on daily life. We also consider whether treatment has been coordinated across providers and whether there are barriers that have made it difficult to sustain care.
This evaluation helps us avoid treating treatment resistance as a one-size-fits-all category. It also helps us discuss IV ketamine infusion therapy, SPRAVATO®, Deep TMS, or other next-step care in the context of the individual rather than as interchangeable solutions.
IV Ketamine for Treatment-Resistant Depression
IV ketamine may be considered for some adults with treatment-resistant depression following a careful psychiatric and medical evaluation. Its psychiatric use is off-label, meaning it is not FDA-approved specifically for depression.
Research has found rapid antidepressant effects for some people with treatment-resistant depression, but response, timing, durability, and side effects vary. Ketamine is not appropriate for everyone, and it should not be presented as a cure or a substitute for comprehensive depression care.
When IV ketamine is considered, we review diagnosis, treatment history, current medications, medical factors, substance-use history, and treatment goals. We also discuss possible short-term effects and the need for ongoing monitoring and follow-up. Our guide to what to expect from IV ketamine therapy offers additional information about candidacy and the treatment process.
SPRAVATO® for Treatment-Resistant Depression
SPRAVATO® treatment is an FDA-approved esketamine nasal spray for adults with treatment-resistant depression. It may be used as monotherapy or in conjunction with an oral antidepressant, depending on the patient’s clinical situation.
SPRAVATO® is administered under direct medical supervision through a restricted REMS program because of important safety considerations, including sedation, dissociation, respiratory depression, abuse, and misuse risks. Patients are monitored after administration before leaving the treatment setting.
SPRAVATO® also has a separate FDA indication for depressive symptoms in adults with major depressive disorder and acute suicidal ideation or behavior when used with an oral antidepressant. It has not been shown to prevent suicide, and emergency evaluation or hospitalization may still be necessary when clinically warranted.
For patients considering this option, our article on how SPRAVATO® works for treatment-resistant depression explains the supervised treatment process in more detail.
Deep TMS for Depression
Deep TMS is a noninvasive treatment delivered by an FDA-cleared device for depressive episodes in adults with major depressive disorder who have not achieved satisfactory improvement with prior antidepressant treatment in the current episode.
Deep TMS uses magnetic pulses to stimulate targeted areas of the brain involved in mood regulation. It is not a medication, and treatment generally involves a series of scheduled sessions over several weeks. Whether it may be appropriate depends on diagnosis, prior treatment response, medical history, and practical considerations such as scheduling and coverage.
Deep TMS should not be described as guaranteed to work or as the right fit for every person with treatment-resistant depression. For some patients, however, it may offer a non-medication treatment option within a broader psychiatric plan.
When Combination Care May Be Discussed
Our practice also offers ketamine + Deep TMS for selected patients. Combination care should not be assumed to be more effective than either treatment alone, and the available research remains limited.
A combined approach may be discussed when a patient’s history, prior response, current symptoms, and treatment goals suggest that it is reasonable to consider. The decision should follow an individualized evaluation, with clear discussion of what is known, what remains uncertain, and how each treatment would fit into a broader care plan.
Moving Beyond Repeated Medication Changes
For many patients, the emotional burden of treatment-resistant depression is not only the symptoms themselves. It is the experience of repeatedly trying to get better and feeling as though each unsuccessful treatment narrows the path forward.
We do not view treatment resistance as a reason to stop looking for answers. It is a reason to reassess the full picture carefully. That may include reviewing medication strategy, strengthening psychotherapy support, addressing sleep or anxiety, considering an interventional treatment, or coordinating care with other clinicians.
The goal is not to promise a specific outcome. It is to help patients understand their options, make informed decisions, and pursue a treatment plan that fits the complexity of their depression.
Frequently Asked Questions
What qualifies as treatment-resistant depression?
Definitions vary, but treatment-resistant depression commonly refers to major depressive disorder that has not improved adequately after at least two antidepressant trials of appropriate dose and duration. A comprehensive evaluation can help determine whether previous treatment was adequate and whether other factors may be affecting recovery.
Is IV ketamine safe for depression?
IV ketamine is not appropriate for every patient. Safety depends on the individual’s medical and psychiatric history, current medications, and risk factors. It can cause short-term effects such as changes in blood pressure, dissociation, nausea, or perceptual changes, which is why treatment should follow a careful evaluation and occur in a supervised clinical setting.
Does insurance cover treatment-resistant depression care in Houston?
Coverage depends on the treatment, insurance plan, diagnosis, treatment history, and medical-necessity criteria. We discuss practical considerations, including coverage questions and self-pay options, during the consultation process.
How long does ketamine treatment take to work?
Some patients notice a change in depressive symptoms soon after treatment, while others do not respond or may need a different approach. The timing, degree, and durability of improvement vary. A consultation can help set realistic expectations about treatment and follow-up.
What if I have tried ketamine before and it did not help?
A previous limited response is important information, but it does not replace a full review of your history. Factors such as diagnosis, treatment setting, medication regimen, dose, treatment frequency, coexisting conditions, and goals of care may all matter. A specialist evaluation can help determine whether another intervention or a different treatment plan may be more appropriate.
Key Takeaways
- Treatment-resistant depression commonly refers to depression that has not improved adequately after multiple antidepressant trials, although definitions vary.
- A thorough reassessment should consider diagnosis, treatment history, therapy, sleep, medical concerns, substance use, and coexisting psychiatric symptoms.
- IV ketamine may be considered for treatment-resistant depression, but psychiatric use is off-label and requires individualized evaluation.
- SPRAVATO® is FDA-approved for adults with treatment-resistant depression and is administered under direct supervision through a REMS program.
- Deep TMS is delivered by an FDA-cleared device for qualifying adults with major depressive disorder who have not improved satisfactorily with prior antidepressant treatment.
- Combination ketamine and Deep TMS protocols may be discussed for selected patients, but evidence remains limited and outcomes vary.
Conclusion
Treatment-resistant depression is one of the most difficult forms of depression to live with, particularly when you have already put substantial effort into treatment without finding adequate relief. But an incomplete response does not mean there are no remaining options.
At our Bellaire clinic, we work with patients who need a more complete review of their depression history and treatment plan. To discuss whether a comprehensive psychiatric evaluation may be appropriate, contact us to request a consultation.
About Dr. Sandhya Prashad
Dr. Sandhya Prashad, M.D., is a board-certified psychiatrist and the founder and medical director of Sandhya J. Prashad, MD, Houston Ketamine Therapeutics, and Houston TMS Therapeutics. She has been in private practice in the Houston area since 2011 and has personally administered more than 9,000 ketamine or esketamine treatments. Her practice focuses on treatment-resistant conditions and interventional psychiatric care.
Works Cited
Arubuolawe, O. O., Folorunsho, I. L., Busari, A. K., Ibeneme, C., & Afolabi, V. (2024). Combination of transcranial magnetic stimulation and ketamine in treatment-resistant depression: A systematic review. Cureus, 16(7), e64712. https://pubmed.ncbi.nlm.nih.gov/39156335/
Gaynes, B. N., Lux, L., Gartlehner, G., Asher, G., Forman-Hoffman, V., Green, J., Boland, E., Weber, R. P., Randolph, C., Bann, C., Coker-Schwimmer, E., Viswanathan, M., & Lohr, K. N. (2020). Defining treatment-resistant depression. Depression and Anxiety, 37(2), 134–145. https://pubmed.ncbi.nlm.nih.gov/31638723/
Murrough, J. W., Iosifescu, D. V., Chang, L. C., Al Jurdi, R. K., Green, C. E., Perez, A. M., Iqbal, S., Pillemer, S., Foulkes, A., Shah, A., Charney, D. S., & Mathew, S. J. (2013). Antidepressant efficacy of ketamine in treatment-resistant major depression: A two-site randomized controlled trial. American Journal of Psychiatry, 170(10), 1134–1142. https://pubmed.ncbi.nlm.nih.gov/23982301/
U.S. Food and Drug Administration. (2012). BrainsWay Deep TMS System: 510(k) summary (K122288). https://www.accessdata.fda.gov/cdrh_docs/pdf12/k122288.pdf
U.S. Food and Drug Administration. (2025). SPRAVATO® (esketamine) nasal spray: Prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/211243s016lbl.pdf
Medical Disclaimer
This blog is provided for educational purposes only and does not constitute medical advice. The information presented here is not intended to diagnose, treat, cure, or prevent any condition. Individual results vary, and the treatments described may not be appropriate for every patient. Please discuss your symptoms and treatment options with a qualified psychiatric provider before making any medical decisions. If you are experiencing a psychiatric emergency or are in crisis, please call 988 (Suicide and Crisis Lifeline) or go to your nearest emergency room.