Trying one antidepressant after another without finding lasting relief can be exhausting. Each new medication may bring another period of waiting, another adjustment to side effects, and another round of uncertainty about whether anything will change.
Some people experience partial improvement but continue to struggle with low energy, disconnection, hopelessness, sleep problems, or difficulty functioning. Others notice little benefit despite multiple medication trials and sustained participation in psychotherapy.
At Thrive Center for Health in Grand Rapids, we work with patients who have reached this point. We do not view an incomplete response as evidence that a person has failed treatment—or that recovery is no longer possible. We see it as a reason to reassess the diagnosis, review what has already been tried, and consider whether a different treatment pathway may be appropriate.
What Treatment-Resistant Depression Means
Treatment-resistant depression, commonly abbreviated as TRD, generally refers to major depressive disorder that has not improved adequately after at least two antidepressant trials given at appropriate doses and for sufficient lengths of time.
That definition provides a useful starting point, but it does not tell the whole story.
Before describing someone’s depression as treatment-resistant, clinicians should consider whether the previous medication trials were truly adequate. A medication may have been stopped early because of side effects. The dose may not have reached a therapeutic level. A patient may have struggled to take it consistently, or another medical or psychiatric condition may have complicated the response.
The diagnosis itself may also need to be reconsidered. Bipolar disorder, PTSD, anxiety, substance use, sleep disorders, hormonal changes, chronic pain, and certain medical conditions can all influence depressive symptoms and affect treatment decisions.
Our approach to depression treatment in Grand Rapids begins with this broader clinical perspective. We want to understand not only which medications you have tried, but what happened during each trial and what may still be contributing to your symptoms.
Why One Antidepressant May Not Be Enough
Antidepressants help many people, but the first medication does not lead to remission for everyone. Large treatment studies have found that the likelihood of remission generally declines as additional medication steps become necessary.
This does not mean trying another medication is pointless. Switching antidepressants, combining medications, adding an augmentation treatment, and integrating psychotherapy can all be reasonable next steps. The appropriate choice depends on the diagnosis, previous response, side effects, medical history, and the symptoms that remain most disruptive.
It is also important to distinguish between response and remission.
A response usually means that symptoms have improved substantially. Remission means that symptoms have decreased to the point that the person is experiencing little or no ongoing depression. Someone may technically respond to medication while still feeling far from well.
When we review a patient’s history, we look for that distinction. A medication that reduced symptoms by half may have provided a meaningful benefit, even if it did not produce remission. That information can help us decide whether the medication should be continued, adjusted, combined with another treatment, or reconsidered.
Our article on how ketamine differs from conventional antidepressants offers additional context about why different treatment mechanisms may be considered after standard options have not been enough.
Why We Reassess Before Recommending Something New
When depression persists, our first question is not simply, “What should we add next?” We begin by asking whether the current diagnosis and treatment history have been fully understood.
A careful reassessment may include:
- Which medications were tried and at what doses
- How long each medication was taken
- Whether symptoms improved partially or temporarily
- Which side effects occurred
- Whether psychotherapy was accessible and suited to the patient’s needs
- Whether there have been periods of unusually elevated mood or reduced need for sleep
- Whether trauma, anxiety, OCD, chronic pain, or sleep disruption is also present
- Whether another medication or health condition could be affecting mood
- Whether the patient is currently experiencing suicidal thoughts or another urgent safety concern
This review can reveal that a treatment was not ineffective so much as incomplete, poorly tolerated, or directed at only one part of a more complex clinical picture.
At Thrive, we provide psychiatric medication management for depression and other mood conditions. For some patients, the most appropriate next step is a thoughtful adjustment to the existing medication plan rather than ketamine therapy.
For others, medication management and ketamine treatment may be coordinated as parts of a broader plan. We make that decision through evaluation and ongoing conversation, not by assuming that every patient with persistent depression needs the same intervention.
Where IV Ketamine May Fit
Most conventional antidepressants influence serotonin, norepinephrine, dopamine, or combinations of these neurotransmitter systems. Ketamine works through different pathways that involve NMDA receptors and glutamate signaling.
Researchers are still studying exactly how these effects produce changes in depression. Current evidence suggests that ketamine influences signaling associated with synaptic function and neuroplasticity, but its antidepressant mechanism is more complex than a simple “brain reset.”
Controlled trials have found that a single IV ketamine infusion can reduce depressive symptoms more quickly than conventional antidepressants in some people with treatment-resistant depression. Repeated-infusion studies have also reported cumulative benefits for some patients.
These findings are clinically meaningful, but they do not guarantee that every patient will respond. The durability of improvement varies, maintenance needs differ, and researchers are still working to define the safest and most effective long-term treatment strategies.
IV ketamine for depression is an off-label use. It has not been approved specifically as a psychiatric treatment, and it should not be presented as a cure or a guaranteed source of rapid relief.
At our clinic, we may consider IV ketamine when a patient has a well-supported diagnosis, an appropriate treatment history, and no medical or psychiatric factors that make the treatment unsuitable. We explain what the evidence supports, where uncertainty remains, and how progress will be monitored before treatment begins. For a broader look at what this care involves, see our ketamine treatment experience overview.
Why Screening Is More Than a Formality
Ketamine therapy does not begin with an infusion appointment. It begins with psychiatric and medical evaluation.
Our ketamine screening process helps us determine whether treatment is appropriate and how it should be structured. We review medical conditions, psychiatric history, current medications, previous treatment responses, cardiovascular considerations, substance-use history, and any other factors that could affect safety.
We also establish a clearer baseline for monitoring symptoms. This allows us to evaluate more than whether a patient felt different during or immediately after an infusion.
We want to know whether treatment is contributing to meaningful changes in mood, interest, energy, functioning, relationships, and the ability to participate in ongoing care. We also monitor for adverse effects and for signs that the treatment plan needs to be adjusted.
Ketamine is not appropriate for every person with depression. A thorough screening process helps us make that determination responsibly.
What IV Ketamine Treatment Involves
During an IV infusion, ketamine is administered through a vein while the patient is monitored by our clinical team. Patients may experience temporary changes in perception, awareness, or their sense of time and surroundings.
Before the appointment, we explain preparation requirements, transportation expectations, monitoring, and what patients may experience during recovery. Patients cannot drive themselves home after an infusion and should plan according to the instructions provided by our team.
Our guide to what happens during a first ketamine infusion provides a more detailed look at the treatment-day process.
A single infusion is not enough to determine the long-term course of care for every patient. When treatment begins, we monitor response across the recommended initial series and discuss whether additional treatment is appropriate based on individual progress.
How Ketamine-Assisted Psychotherapy May Fit
Some patients may also consider ketamine-assisted psychotherapy, or KAP. This approach combines ketamine treatment with psychotherapeutic preparation and integration.
The therapy component gives patients an opportunity to prepare for the experience, process thoughts or emotions that arise, and consider how insights might be applied outside the treatment setting.
Research on combining ketamine with psychotherapy is developing, but it remains heterogeneous. Studies have used different medication routes, doses, therapy models, session structures, and patient populations. As a result, we cannot assume that KAP will produce better or longer-lasting outcomes for every patient.
We discuss KAP as one possible approach—not as an automatic upgrade from standard infusion care. Our overview of how ketamine-assisted psychotherapy works explains how we structure this service and what patients may want to consider.
We Can Coordinate With Your Existing Providers
Considering ketamine therapy does not necessarily mean leaving your current therapist, psychiatrist, or primary care provider.
Many patients continue working with existing professionals while receiving specialized care from us. With the patient’s permission and when coordination is appropriate, we can communicate with those providers to support continuity and reduce the risk of conflicting treatment plans.
This is especially important when another clinician is prescribing antidepressants, mood stabilizers, sleep medication, or other treatments that may affect candidacy or monitoring.
Patients should never stop an antidepressant or change its dose without guidance from the prescribing provider. Even when a medication seems ineffective, discontinuing it abruptly can cause withdrawal symptoms or worsen the clinical situation.
Planning for Cost and Access
We understand that the financial side of treatment can be a significant concern. Coverage, billing arrangements, and patient responsibility may vary based on the service and insurance plan.
Because these details can change, we encourage patients to speak with our team about current pricing and what to expect before scheduling treatment. Patients can also review our ketamine treatment cost page for general guidance on what to anticipate financially. We want patients to have clear information before making a financial commitment.
Cost should be part of an honest treatment conversation. It should not be minimized, and patients should not feel pressured to begin a service before they understand the likely expense and the clinical rationale.
Rebuilding Trust After Difficult Treatment Experiences
By the time some patients reach us, they have spent years trying treatments that did not provide enough relief. They may have felt dismissed, blamed, rushed through appointments, or told to lower their expectations.
We understand why those experiences can erode trust.
Our role is not to promise that we have one answer previous providers missed. Our role is to listen carefully, review the complete history, explain the options honestly, and create a treatment plan that reflects the individual rather than a standard script.
We have designed our Grand Rapids clinic to feel calm, private, and supportive while maintaining the medical monitoring required for treatment. Our care culture is grounded in being compassionate, approachable, inspiring, dedicated, and authentic.
We want patients to feel comfortable asking difficult questions—including questions about evidence, risks, cost, uncertainty, and what will happen if a treatment does not work.
Frequently Asked Questions
What qualifies as treatment-resistant depression?
Treatment-resistant depression is commonly defined as major depressive disorder that has not improved adequately after at least two antidepressant trials at appropriate doses and durations. Definitions vary, and a clinician should also review adherence, side effects, diagnostic accuracy, psychotherapy history, co-occurring conditions, and other factors that may explain why treatment has not worked as expected.
How quickly can IV ketamine affect depression symptoms?
Controlled studies have observed reductions in depressive symptoms within approximately one day of a single infusion for some participants. In clinical practice, the timing and degree of improvement vary. Some patients notice changes early in an initial series, while others respond later or do not experience a meaningful benefit. An early effect does not guarantee that improvement will continue without additional care.
Does everyone begin with a standard series of infusions?
Treatment planning is individualized. Published research and clinical protocols often use a series of infusions, but the appropriate schedule depends on the patient’s evaluation, response, tolerability, and the clinic’s current protocol. We explain the proposed schedule and how progress will be assessed before treatment begins.
Is IV ketamine covered by insurance?
Coverage and billing arrangements vary. Patients should confirm their current benefits and speak with our team about present pricing and financial expectations. We avoid making blanket statements about what an insurer will or will not cover because individual plans and billing circumstances differ.
What is the difference between an IV infusion and KAP?
An IV ketamine infusion focuses on administering and monitoring the medication in a clinical setting. KAP combines ketamine treatment with psychotherapeutic preparation and integration. Neither approach is automatically right for every patient. We consider treatment history, clinical needs, goals, and patient preferences when discussing the available options.
Can ketamine be considered when depression occurs with another diagnosis?
Possibly. Depression often occurs alongside anxiety, PTSD, OCD, chronic pain, or other conditions. Co-occurring diagnoses do not automatically qualify or disqualify someone. We evaluate the full clinical picture, confirm which condition is being targeted, and determine whether ketamine is appropriate for that individual.
What should I do if my depression feels dangerous right now?
Ketamine consultation is not a substitute for emergency care. Call or text 988 if you are experiencing suicidal thoughts or an emotional crisis. Call 911 or go to the nearest emergency department if you may act on those thoughts, cannot remain safe, or believe there is an immediate danger to yourself or someone else.
Key Takeaways
- Treatment-resistant depression commonly describes depression that has not improved adequately after at least two appropriate antidepressant trials.
- An incomplete response should lead to careful reassessment of the diagnosis, treatment history, side effects, co-occurring conditions, and current safety needs.
- Antidepressants can still have a role after an unsuccessful trial through switching, augmentation, or a more individualized medication strategy.
- IV ketamine works through pathways that differ from conventional antidepressants and may reduce symptoms relatively quickly for some patients.
- The benefits of ketamine vary, may not be permanent, and cannot be guaranteed.
- IV ketamine for depression is an off-label use and should follow thorough psychiatric and medical screening.
- Medication management, psychotherapy, ketamine treatment, and coordinated care may each play a role depending on the patient.
- Psychiatric medications should never be stopped or changed without guidance from the prescribing provider.
When Antidepressants Are Not Enough, We Look More Closely
Trying multiple antidepressants without achieving remission does not mean your depression is untreatable. It means the plan deserves a closer look.
At Thrive Center for Health, we take time to review what you have already tried, what helped, what caused problems, and what may not yet have been addressed. Depending on what we learn, the next step may involve psychiatric medication management, IV ketamine therapy, ketamine-assisted psychotherapy, coordination with your current providers, or another recommendation.
We will not reduce a complex treatment history to a sales pitch or promise an outcome we cannot guarantee. We will explain what the evidence shows, discuss the limitations, and help you decide whether one of our services is an appropriate next step.
When you are ready to begin that conversation, you can contact our Grand Rapids team.
About Thrive Center for Health
At Thrive Center for Health in Grand Rapids, Michigan, we provide specialized care for patients with complex mental health and chronic pain conditions, including people who have not found adequate relief through standard treatment.
Our clinic includes private treatment rooms, continuous clinical monitoring, and an environment designed to help patients feel safe, respected, and supported. We provide IV and IM ketamine therapy, ketamine-assisted psychotherapy, psychiatric medication management, and complementary patient resources.
Our approach is grounded in individualized evaluation, honest communication, and compassionate care from the first consultation through each stage of treatment.
Thrive Center for Health is located at 847 Parchment Drive SE, Suite 105, Grand Rapids, MI 49546.
Medical Disclaimer
This content is provided for educational purposes only and does not constitute medical advice, diagnosis, or an individualized treatment recommendation. IV ketamine for depression is an off-label use and may not be appropriate for every patient. Individual results vary, and no outcome can be guaranteed. Always consult a qualified healthcare provider before starting, stopping, or changing a medication or treatment.
If you are experiencing suicidal thoughts or an emotional crisis, call or text 988. Call 911 or go to the nearest emergency department if there is an immediate danger to you or someone else.
Works Cited
Kew, B. M., Porter, R. J., Douglas, K. M., et al. (2023). Ketamine and psychotherapy for the treatment of psychiatric disorders: A systematic review. Journal of Psychiatric Research, 163, 1–13.
McIntyre, R. S., Alsuwaidan, M., Baune, B. T., et al. (2023). Treatment-resistant depression: Definition, prevalence, detection, management, and investigational interventions. World Psychiatry, 22(3), 394–412.
Murrough, J. W., Iosifescu, D. V., Chang, L. C., et al. (2013). Antidepressant efficacy of ketamine in treatment-resistant major depression: A two-site randomized controlled trial. American Journal of Psychiatry, 170(10), 1134–1142.
National Institute on Drug Abuse. (2024). Ketamine. National Institutes of Health.
Phillips, J. L., Norris, S., Talbot, J., et al. (2019). Single, repeated, and maintenance ketamine infusions for treatment-resistant depression: A randomized controlled trial. American Journal of Psychiatry, 176(5), 401–409.
Rush, A. J., Trivedi, M. H., Wisniewski, S. R., et al. (2006). Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report. American Journal of Psychiatry, 163(11), 1905–1917.
Sanacora, G., Frye, M. A., McDonald, W., et al. (2017). A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry, 74(4), 399–405.