What can I do about treatment-resistant depression (TRD)?

This article was created in partnership with Osmind.

It’s hard when you’re taking medication that is supposed to treat your depression, but nothing seems to be helping. If you’ve tried two or more treatments and you still experience symptoms of depression, you might have treatment-resistant depression (TRD).

What is treatment-resistant depression (TRD)?

If a doctor diagnoses you with TRD, this usually means that you have not responded to at least two different antidepressants after taking them with proper dose and duration. If symptoms of depression, such as sadness, an “empty” mood, hopelessness, decreased energy and concentration, thoughts of or attempts at suicide, etc., continue after you have tried two or more treatments, you may have TRD.

If you have TRD, you are not alone: TRD affects about one third of Americans with depression [1]. Further, being diagnosed does not mean that you have no treatment options; there are many treatment options that have been shown to work for TRD patients.

How is TRD treated?

There are many ways to treat TRD. In addition to the wide variety of traditional antidepressants available, there are newer medical treatments such as psychedelic medicine and transcranial magnetic stimulation (TMS).

Psychedelic medicine—namely ketamine (FDA-approved as an anesthetic but widely prescribed off-label for mental health conditions) and esketamine (FDA-approved for TRD)—have been shown to work for patients with TRD [2]. When used correctly, they are very effective as a treatment for depression.

Both of these treatments have temporary effects. In order to continue their antidepressant effects, they must be given to patients more than once. The long-term effects and safety of repeated ketamine and esketamine treatments are still being determined. However, many clinicians have determined it to be a safe and effective treatment for those with TRD. If you want to learn more about what a treatment session might look like, Osmind has clinician- and patient-validated guides for both ketamine and esketamine.

Transcranial magnetic stimulation (TMS) is another FDA-approved treatment that is effective in reducing symptoms of TRD. It’s a non-invasive treatment in which a doctor will apply brief magnetic pulses to your brain for about 40 minutes once a day, five days a week for six or more weeks. This is typically done in a doctor’s office and is performed on an outpatient basis. There are different types of TMS, so it is important to ask your doctor for more clarification. If this treatment works for you, your symptoms may improve or go away completely.

Antidepressants may still work for people with TRD. It is possible that you just haven’t found one that works best for you, so this may still be an option that is available. Different antidepressants will work in different ways, and medications take from two or more weeks to become fully effective [3]. Sometimes you might need a higher dose of a medication that you’re trying for it to be effective. Many people find that combining more than one antidepressant can be helpful. Be sure to talk with your doctor about options if the antidepressant that you’re trying is not working.

What other options do I have?

Not all treatments for TRD involve medication. Therapy is one of the most effective treatments for depression. Therapy can be a long and sometimes difficult process, but stick with it—it can be life-changing as well. If you’ve worked with a therapist already and it hasn’t helped, try searching for a different kind of therapist who might be a better fit for you.

There are also things you can do on your own. Lifestyle changes, like improving your eating, sleeping, and exercise habits, can be helpful for many people.

Here are a few final things to keep in mind as you seek treatment for TRD:

  • If you are experiencing any debilitating symptoms (anything that prevents you from functioning at work or school, or if you’re thinking seriously about suicide), be sure to seek help right away. A doctor or therapist will be able to help ensure that you receive the treatment that you need as soon as possible.
  • Keep track of your mood and symptoms while seeking and trying new treatments. You can do this by writing in a journal, on a calendar or even an app. This can be shared with your doctor to ensure that you are getting the best treatment possible
  • Sharing your own experiences and learning about other options can lead to finding a treatment that works better for you. You can refer to the MHA DIY Resources page to find tools to help you such as the Osmind community.

  1. Wiles N, Thomas L, Abel A, et al. (2014). Clinical effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: the CoBalT randomised controlled trial. Health Technology Assessment, No. 18.31. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK261988/
  2. P Molero, J.A. Ramos-Quiroga, R. Martin-Santos, et al. (2018). Antidepressant Efficacy and Tolerability of Ketamine and Esketamine: A Critical Review. CNS Drugs, 32. Retrieved from https://link.springer.com/article/10.1007/s40263-018-0519-3
  3. Gin S Malhi, Erica Bell, Grace Morris, et al. The delay in response to antidepressant therapy: A window of opportunity? Australian & New Zealand Journal of Psychiatry, 54, 2. Retrieved from https://journals.sagepub.com/doi/full/10.1177/0004867419900313

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