Trying medication after medication without feeling meaningfully better can be exhausting. It can also make depression feel permanent or make it seem as though you have run out of options.
At H3O Wellness, we work with patients in Twin Falls and across southern Idaho who need a more careful look at what has not worked, what may have been missed, and what treatment options may be appropriate to discuss next. When depression does not respond as hoped to standard medication, the next step is not automatically another prescription. It is a thoughtful, individualized evaluation.
What Treatment-Resistant Depression Means
Treatment-resistant depression, often called TRD, does not mean depression is untreatable. The term is generally used when someone with major depressive disorder has not had an adequate response to at least two antidepressant trials that were appropriate in dose and duration.
That definition is helpful, but it is not a substitute for a clinical assessment. Medication trials can be affected by side effects, treatment duration, medication interactions, access to therapy, co-occurring conditions, and other factors that deserve attention before a person is labeled “out of options.”
Depression is not a personal failure, and needing a different approach is not a sign that you have done anything wrong. It means your care may need to be reassessed with greater detail and a broader range of evidence-informed options in mind.
Start With a More Complete Evaluation
Before considering an interventional treatment, we begin by looking beyond the number of medications on a list. A comprehensive evaluation may include your symptoms, treatment history, current medications, prior therapy experience, medical history, safety considerations, and practical needs.
For some patients, the next step may still involve medication management, psychotherapy, or more support around sleep, stress, substance use, or another factor that affects mood. For others, an alternative treatment may be appropriate to explore.
Our psychiatric services are designed to support individualized mental health care rather than a one-size-fits-all pathway. We want patients to understand the potential benefits, limitations, time commitments, and safety considerations of every option before deciding how to move forward.
Treatment Options That May Be Worth Discussing
When standard antidepressants have not provided enough relief, several treatments may be part of the conversation. No option is automatically right for every person, and treatment recommendations should always follow an appropriate evaluation.
TMS Therapy
TMS therapy is an FDA-cleared, noninvasive treatment that uses magnetic pulses to stimulate targeted brain circuits involved in mood regulation. It does not require anesthesia and is typically delivered through a series of outpatient sessions over several weeks.
TMS may be considered for adults with depression who have not benefited enough from medication or who have struggled with medication side effects. The treatment schedule can require a meaningful time commitment, so it is important to discuss what a course of care may involve before starting.
For a closer look at the treatment process, read our guide to FDA-cleared TMS therapy depression treatment.
SPRAVATO® Treatment
SPRAVATO® treatment uses esketamine, a prescription nasal spray approved for adults with treatment-resistant depression. It is administered under direct medical supervision and includes post-treatment monitoring.
Because SPRAVATO® has specific safety requirements, candidacy depends on more than a depression diagnosis alone. Your medical history, current medications, blood pressure, treatment history, and ability to complete monitored visits are all important considerations.
Our article on SPRAVATO® for depression in Twin Falls explains more about what the treatment may involve.
IV Ketamine
Ketamine for depression may also be discussed for some patients with treatment-resistant depression. Its use for depression is off-label, meaning it is not FDA-approved specifically for that purpose.
Research suggests that IV ketamine may help some adults with depression that has not responded to standard treatment, but results vary. It is not appropriate for everyone, and the research continues to develop around long-term treatment approaches, safety, and who may benefit most.
A clinical evaluation should include a discussion of potential risks, possible benefits, alternatives, and how IV ketamine might fit into a broader mental health plan. You can also explore our overview of ketamine for treatment-resistant depression.
Choosing the Right Next Step
TMS, SPRAVATO®, and IV ketamine are different approaches. They involve different treatment schedules, safety considerations, monitoring needs, insurance considerations, and levels of evidence.
The goal is not to decide which treatment is “best” in the abstract. It is to understand which option, if any, may be a reasonable fit for your diagnosis, treatment history, preferences, medical profile, and day-to-day life.
Some people may benefit from a nonmedication option such as TMS. Others may meet criteria to discuss SPRAVATO® or off-label IV ketamine. Others may benefit most from continued psychiatric care, psychotherapy, medication adjustments, or a combination of supports.
No treatment should be presented as a guarantee. But depression that has not improved with medication may still respond to a different, carefully considered approach.
Frequently Asked Questions
What counts as an adequate antidepressant trial?
An adequate trial generally means taking a medication at a therapeutic dose for enough time to evaluate its effect, when it is tolerated and clinically appropriate. Your provider will review the details of prior medications rather than simply counting how many you have tried.
Does treatment-resistant depression mean nothing will work?
No. Treatment-resistant depression means that standard approaches have not provided enough relief so far. It can be a reason to reassess your diagnosis, treatment history, and the range of options available.
Is TMS different from medication?
Yes. TMS is a device-based treatment that uses magnetic stimulation rather than an antidepressant medication administered during each session. You should not make changes to current medications without speaking with your prescribing provider.
Is SPRAVATO® the same as IV ketamine?
No. SPRAVATO® is esketamine nasal spray with FDA-approved uses for adults with treatment-resistant depression. IV ketamine is a different medication approach and is used off-label for depression. The treatments have different administration, monitoring, safety, and eligibility considerations.
Can SPRAVATO® replace emergency mental health care?
No. SPRAVATO® has an FDA indication for depressive symptoms in adults with major depressive disorder and acute suicidal ideation or behavior when used with an oral antidepressant. However, it has not been shown to prevent suicide or reduce suicidal thoughts or behavior, and it does not replace hospitalization or emergency care when clinically needed.
Will insurance cover advanced depression treatment?
Coverage varies by treatment and insurance plan. TMS and SPRAVATO® may require prior authorization or specific eligibility criteria. IV ketamine for depression is often not covered because it is an off-label use. We encourage patients to discuss coverage questions with their insurer and our team before beginning care.
What should I do if I feel unsafe or am considering self-harm?
Do not wait for a routine appointment or rely on a blog for crisis care. Call or text 988 to reach the Suicide & Crisis Lifeline, call 911, or go to the nearest emergency department if you are in immediate danger or cannot stay safe.
Key Takeaways
- Treatment-resistant depression usually refers to depression that has not responded adequately to at least two appropriate antidepressant trials.
- A careful reassessment can help clarify whether medication changes, therapy, TMS, SPRAVATO®, off-label IV ketamine, or another approach should be considered.
- TMS is FDA-cleared for treatment-resistant depression and is delivered through a series of outpatient sessions.
- SPRAVATO® is an FDA-approved esketamine nasal spray for adults with treatment-resistant depression and requires supervised administration and monitoring.
- IV ketamine may be discussed as an off-label option for depression, but it is not appropriate for every patient and cannot guarantee results.
Moving Forward When Medication Has Not Been Enough
Depression that has not responded to medication can be discouraging, but it does not mean you are out of options. It may mean that your care needs a more complete evaluation and a different conversation about what comes next.
At H3O Wellness, we offer evidence-informed psychiatric care for patients exploring TMS, SPRAVATO®, IV ketamine, and other treatment approaches. Our role is to help you understand your options clearly, weigh them carefully, and make decisions that fit your individual needs. If you are ready to take the next step, contact us to schedule a consultation.
About H3O Wellness
H3O Wellness is an interventional psychiatry and mental wellness practice with offices in Twin Falls and Burley, Idaho. Our team provides psychiatric services alongside advanced treatment options including TMS therapy, SPRAVATO®, and ketamine treatment.
We believe in individualized care that treats patients with respect and dignity while helping them explore practical, clinically appropriate next steps.
Medical Disclaimer
The content of this blog is provided for educational purposes only and does not constitute medical advice. Individual results vary, and no treatment outcome can be guaranteed. The information presented here is not a substitute for professional medical evaluation, diagnosis, or treatment.
If you are experiencing depression or a mental health crisis, seek help from a qualified healthcare provider or emergency service. Treatments described in this article may not be appropriate for every patient. Always discuss your symptoms, medical history, and treatment options with a licensed provider before making healthcare decisions.
Works Cited
Gaynes, B. N., Lux, L., Gartlehner, G., et al. (2020). Defining treatment-resistant depression. Depression and Anxiety, 37(2), 134–145.
Lam, R. W., Kennedy, S. H., Adams, C., et al. (2024). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 update on clinical guidelines for management of major depressive disorder in adults. The Canadian Journal of Psychiatry, 69(9), 641–687.
National Institute of Mental Health. (n.d.). Brain stimulation therapies.
Seshadri, A., Prokop, L. J., & Singh, B. (2024). Efficacy of intravenous ketamine and intranasal esketamine with dose escalation for major depression: A systematic review and meta-analysis. Journal of Affective Disorders, 356, 379–384.
U.S. Food and Drug Administration. (2025). SPRAVATO® (esketamine) nasal spray prescribing information.