# Treatment Resistant Depression: What It Is and What Helps

> Treatment resistant depression means two antidepressants have not helped enough. Learn how it is diagnosed and next options, from lithium to TMS and Spravato.

URL: https://foundationmedicalgroup.org/treatment-resistant-depression/
Published: 2026-10-11
Updated: 2026-10-11

Treatment resistant depression (TRD) means depression whose symptoms haven’t improved enough after at least two antidepressants, each taken at a good dose for long enough. And it wears you down, when each new prescription starts with hope and ends in another long wait. But it doesn’t mean you’re out of treatment options. Next steps include medication changes, therapy, TMS, Spravato and ketamine, and a psychiatrist helps choose the order.
What Is Treatment Resistant Depression? TRD is major depressive disorder that hasn’t responded well enough to at least two antidepressants. Each one has to be taken at an adequate dose, for an adequate length of time, and as prescribed. It doesn’t mean nothing will work.
A review in Molecular Biomedicine uses this definition. In plain words, an “adequate” trial has three parts:
Dose. The antidepressant medication was taken at a dose high enough to have a fair chance of working. Time. It was taken for long enough to judge the result. Taking it as prescribed. Doses were not often missed or stopped early. Treatment resistance describes how your depressive disorder has responded so far. It isn’t a judgment about you. It’s not your fault, either, even if it feels that way after months of trying. It simply tells your care team that two medication trials weren’t enough, and that it’s time to look at other paths.
How Is TRD Diagnosed? It starts with a full psychiatric evaluation. In psychiatry, the first step is to look closely at the antidepressant medications you’ve already tried. At FMG, that’s part of what our clinicians review at the evaluation. Which ones did you take, at what dose, for how long, and did you take them as prescribed? Sometimes a medicine that seemed to fail was never given a full, adequate trial. That can be frustrating to hear. It can also be a relief, because it means that option isn’t really used up yet.
Your clinician also looks at your whole mental health picture. Signs of bipolar disorder, anxiety disorders, substance abuse or personality disorders can change the plan, so they ask about these with care. They’ll also go over your current depression symptoms, how long they’ve lasted and how they affect daily life.
Foundation Medical Group offers psychiatric evaluation in Virginia, Utah, Georgia and Texas. That means the Richmond flagship on Busy Street, our American Fork clinic on the Wasatch Front, the Decatur office in metro Atlanta and the North Dallas office on LBJ Freeway. Learn what the first visit involves on our psychiatric evaluation page.
How Common Is TRD? If two antidepressants haven’t helped, that’s more common than it probably feels right now. According to the Molecular Biomedicine review, about 30% of people with depression don’t benefit from trying antidepressants one after another. Close to a third, in other words. It’s a common problem, and a heavily studied one.
The National Institute of Mental Health (NIMH) supports research on new therapies for patients with depression who do not improve after multiple treatments. Patients living with this kind of mental illness are an active focus of study.
What Causes TRD? There’s no single known cause. Which is maddening when you just want to know why. Researchers are studying the biology of mood regulation, and the Molecular Biomedicine review looks at molecular mechanisms behind resistant depression.
In day-to-day care, the first question is usually practical. Did a treatment really fail, or was something else going on? Common reasons a medicine may look like it didn’t work include a dose that was too low, a trial that was too short, missed doses, or another condition that wasn’t found yet. These are checked first.
Your clinician may also ask about chronic stress, sleep, health problems and other parts of your life. This helps them understand your depressive symptoms over time, so the next plan fits you and gives you the support you actually need.
What Are the Treatment Options for TRD? Now, the more hopeful part. There are many treatments to try after two medicines. Here’s the usual ladder of next steps.
Medication changes and augmentation A prescriber may switch you to a different class of antidepressant, such as selective serotonin reuptake inhibitors, tricyclic antidepressants or monoamine oxidase inhibitors. Another option is augmentation. That means adding a second medication to the one you already take. The Molecular Biomedicine review lists augmentation, including lithium, among the options. Lithium and other mood stabilizers are managed by a prescriber, who guides every change. Sounds like a lot of moving parts? It is, a little. That’s exactly why you shouldn’t sort it out alone.
Psychotherapy Talk therapy can be used alongside medication. Options include cognitive behavioral therapy, interpersonal therapy, and acceptance and commitment therapy. Foundation Medical Group offers talk therapy, including CBT, DBT and ACT. Sessions are by secure video in Virginia, Utah, Georgia and Texas, and in person at our Richmond, VA clinic. Psychotherapy gives you skills and support for coping with symptoms while other treatments do their work.
Brain stimulation therapy When conventional treatments and standard treatments haven’t helped enough, brain stimulation therapy is another path. NIMH notes that repetitive transcranial magnetic stimulation (rTMS) is FDA-cleared for treatment-resistant depression. Electroconvulsive therapy (ECT) is used for severe treatment-resistant depression, usually over 6 to 12 treatments. FMG offers TMS in Richmond, VA. We do not offer ECT or VNS.
Spravato and ketamine Spravato (esketamine nasal spray) is FDA-approved for treatment-resistant depression in adults, used alone or with an oral antidepressant. Per its FDA label, patients are monitored for at least 2 hours at each session. Ketamine itself is different. The FDA states that ketamine is not approved for any psychiatric disorder, so IV or IM ketamine for resistant depression is an off-label use. Still, the review lists ketamine among TRD options. FMG offers both Spravato and ketamine at our Richmond, VA clinic only.
Side note, because people ask: why is TMS “cleared” while Spravato is “approved”? The FDA tends to use “cleared” for many medical devices and “approved” for drugs. TMS is a device. Spravato is a medicine. So the different words reflect different review paths, not a ranking of which one works better. Anyway, back to the bigger question of how these options stack up.
TMS Therapy, Spravato, Ketamine and ECT: How Do These Treatments Compare? Each of these is a treatment option for resistant depression when medicines haven’t brought enough relief. We don’t rank them by how well they work, because the sources here don’t compare them head to head. That might feel unsatisfying. Fair enough. But a ranking without real comparison data wouldn’t help you.
TMS (rTMS) Spravato (esketamine) IV/IM ketamine ECT What it is Magnetic brain stimulation Esketamine nasal spray Ketamine by infusion or injection Electrical brain stimulation FDA status for TRD FDA-cleared FDA-approved for TRD in adults Not FDA-approved for any psychiatric disorder Used for severe TRD Visits (from sources) See the FMG TMS page Monitoring at least 2 hours each session Set by your provider Usually 6 to 12 treatments Offered at FMG Richmond VA Richmond VA Richmond VA (self-pay; some plans cover a portion) Not offered The most effective treatment for you depends on your history, your health and what you’ve already tried. For details on TMS therapy, see TMS in Richmond. For the nasal spray, see Spravato in Richmond.
Where to Get TRD Care in Richmond, VA Our Richmond clinic at 11600 Busy Street, Suite 203, Richmond, VA 23236 offers three options for resistant depression in one place. For patients around RVA, Midlothian included, that’s handy: you aren’t driving across town to a different office for each one. The three:
TMS therapy. Offered in Richmond only. Spravato. Offered in Richmond only. IV and IM ketamine. Self-pay; some plans cover a portion. See the ketamine section of our treatments page. If you’ve tried at least two antidepressants without enough relief from your symptoms, it’s a good time to ask about these options. Psychiatry and medication management are also available at our American Fork, UT and Dallas, TX clinics, and psychiatric evaluation is offered in Decatur, GA. TMS, Spravato and ketamine are offered in Richmond, VA only. So if you’re on the Wasatch Front or in North Dallas, that’s a real trip, and it’s worth talking it through with your local prescriber first.
For insurance, call to confirm coverage. In Virginia, Medicare is not accepted. FMG also offers addiction treatment with medication, but we do not offer ECT, detox, IOP, PHP or residential care. Visit our Virginia clinic page to reach the Richmond team about depression treatment and other mental health treatment.
Can Treatment Resistant Depression Be Treated? Yes. Many options remain after two medicines, even for severe depression. Relief from symptoms may take more than one try. So steady support from a care team matters. NIMH lists brain stimulation as one type of depression treatment, and it funds research on new therapy options for people who have not improved.
Feeling worn down by round after round of trying is normal. Bone-tired, even. Let the people you trust support you, and tell them how it’s actually going, not the polished version. Keep talking with your prescriber about your depressive symptoms and what has helped your mental health, and never stop or change a medicine on your own.
If you are having suicidal thoughts, get help now. Call 911 or go to the nearest emergency room. Do not wait for a scheduled appointment.
Key Takeaways Treatment-resistant depression means two adequate antidepressant trials without enough relief. About 30% of people with depression do not benefit from trying antidepressants one after another. Dose, time and other conditions are checked first. Treatment options include augmentation such as lithium, therapy, TMS, ECT, Spravato and ketamine. TMS, Spravato and ketamine are offered at FMG’s Richmond, VA clinic. FAQ What is the best treatment for treatment-resistant depression? There is no single best option for everyone. The right choice depends on your history, your symptoms and which treatments you have already tried. A psychiatrist may suggest augmentation, therapy, TMS, Spravato or ketamine, and will help you decide the order.
Does lithium help treatment-resistant depression? Lithium augmentation, which means adding lithium to an antidepressant, is one of the options listed for treatment-resistant depression. It should only be started and managed by a prescriber who knows your full history.
Is ketamine FDA-approved for treatment-resistant depression? No. Ketamine is not FDA-approved for any psychiatric disorder, so its use for depression is off-label. Esketamine, sold as Spravato, is the related medicine that is FDA-approved for treatment-resistant depression in adults.
How many ECT treatments are usually needed? According to NIMH, a course of electroconvulsive therapy is usually 6 to 12 treatments. Foundation Medical Group does not offer ECT, but a psychiatrist can help you understand whether it is worth exploring elsewhere.
Is TMS FDA-cleared for treatment-resistant depression? Yes. NIMH notes that repetitive transcranial magnetic stimulation (rTMS) is FDA-cleared for treatment-resistant depression. Foundation Medical Group offers TMS at its Richmond, VA clinic.
Sources Molecular Biomedicine via PMC, Treatment-resistant depression: molecular mechanisms and management. National Institute of Mental Health, Brain Stimulation Therapies. U.S. Food and Drug Administration (Drugs@FDA), SPRAVATO (esketamine) nasal spray prescribing information (2025). U.S. Food and Drug Administration, Warning Letter: Ketamine Store (www.ketaminestore.org), 06/23/2026. National Institute of Mental Health, Depression.