Support for treatment-resistant depression (TRD)

If initial treatments for depression have not helped enough, there are other treatment options that may help. These options are generally considered after standard treatments, such as two or more antidepressants. There are many reasons why a treatment may not work well enough, and your healthcare provider can help you find an approach that is right for you. Some of these treatments are part of an approach called interventional psychiatry.

Treatment-resistant depression (TRD) is a term used when major depressive disorder (MDD) does not improve enough after trying treatment with antidepressant medication. Your care team can help you understand your options and choose a treatment based on your needs and goals.

What to expect from support for TRD

If your treatment for MDD is not working well enough, your health care provider may suggest other treatment options. If they are not a medical doctor, they may refer you to a psychiatrist or other doctor for care. Sometimes more than one treatment may be used at the same time.

Your care team will talk with you about the benefits, risks and possible side effects of each treatment option to help you make informed decisions about your care.

Depending on your needs, treatment may include changes to your medication, psychotherapy, such as CBT, a medical treatment that affects brain activity or another approach.

Psychotherapy is often an important part of treatment for TRD. It is usually combined with other treatments to help improve symptoms and build coping skills. Your care team may use questionnaires or other assessments to track your symptoms and understand how well treatment is working.

All medical treatments can have side effects. Medical treatments are given under a doctor’s care. Your doctor will work with you to see how the treatment is working and how your symptoms are changing. Your care team will also check on your safety and how you are feeling.

What treatments may help with TRD?

Treatments for TRD may include:

Changing the dose of your current antidepressant or adding another antidepressant
Adding another medication, such as an antipsychotic or a ketamine-based treatment
Psychotherapy, such as cognitive behavioral therapy (CBT), which may help improve symptoms and support long-term recovery
Repetitive transcranial magnetic stimulation (rTMS), a noninvasive treatment that uses magnets to stimulate an area of the brain
Electroconvulsive therapy (ECT), a treatment that uses electrical signals to affect brain activity

Some people may also get support with sleep, physical activity or stress management as part of their care.

Benefits of TRD care

Treatment for TRD may help improve:

Mood and sense of well-being
Ability to focus
Sleep
Energy level
Self-esteem and confidence
Daily life

It may take time to notice changes, and treatment results can vary from person to person.

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Sources

Cleveland Clinic, Major Depressive Disorder (Clinical Depression): Symptoms. May 28, 2026.

Cleveland Clinic, Treatment-Resistant Depression: What It Is & Symptoms. May 16, 2023.

Johns Hopkins Medicine, Treatment-Resistant Depression. Accessed June 22, 2026.

Johns Hopkins Medicine, Major Depression. Accessed June 22, 2026.

Integrated Behavioral Health of Louisiana, Treatment Resistant Depression. Accessed June 22, 2026.

PMC, Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions. September 15, 2023.