What’s the Difference Between TRD and MDD?

While many people have heard the term Major Depressive Disorder (MDD), fewer have probably heard the term Treatment-Resistant Depression (TRD). But what does each really mean? At first glance, they might sound like totally separate conditions, but they are very closely related. TRD isn’t a different diagnosis altogether, it’s a specific form of MDD. TRD is MDD that does not respond to traditional treatment. It’s important to understand the distinction because it can shape your path to recovery. 

What is Major Depressive Disorder?

MDD is one of the most common mental health conditions that affects millions of people worldwide. It’s different than feeling moments of sadness, but instead, symptoms persist and start to interfere with daily life. Common signs of MDD include:

• Long-lasting feeling of sadness
• Loss of interest in activities once enjoyed
• Changes in sleep and appetite
• Fatigue or low energy
• Trouble making decisions or concentrating

Doctors will usually diagnose MDD when these symptoms last more than two weeks and are affecting your daily functioning at work, school, or home. When doctors initially treat MDD, they normally start with antidepressant medication and/or talk therapy. Making lifestyle changes also helps to ease symptoms. Changes include exercise, consistent sleep schedules, and mindfulness. For a lot of patients, both of these approaches will bring relief. But for some, it does not always.

What is Treatment-Resistant Depression (TRD)?

TRD is what doctors call it when a patient with MDD does not improve after trying two different antidepressants, taken at the correct dose and for an adequate amount of time. This does not mean a person has a different kind of depression, they still have MDD. The difference is in how the condition responds, or does not, to traditional treatments. 

There are a few reasons you may not respond to standard treatments. Brain chemistry or genetics can have a role in how the body responds. Others may have other medical or mental health conditions that complicate treatment. For some, medication can bring partial relief but still leave some symptoms to linger. TRD can feel discouraging, because you’re doing everything to help yourself get better, but you aren’t seeing any of the progress. It’s important to remember that TRD does not mean you are untreatable, it means that your depression may need to be tailored or you may need an alternative approach.

How Are They Different?

MDD and TRD share the same symptoms. Instead, the difference lies in how the depression responds to treatment.

• MDD is the broader diagnosis, and most people will respond to traditional treatments (medication and therapy).
• TRD is when the usual approaches don’t bring enough relief, which signals that alternative or advanced therapies are needed to see results.

This distinction helps doctors and patients make changes and adjust expectations to focus on what to try next, instead of staying on the same treatment path that hasn’t worked.

Why the Distinction Matters

Understanding the difference between MDD and TRD brings clarity. If standard treatments have not worked, it does not mean there are no options left. It simply means the depression falls into the TRD category, and this helps to guide your next steps. TRD often called for treatments beyond traditional antidepressants, such as:

• Transcranial Magnetic Stimulation (TMS): A non-invasive and drug-free treatment that sends magnetic pulses to stimulate areas of the brain associated with mood regulation.

• Spravato (esketamine): A nasal spray that targets the glutamate system. It helps to restore and trigger new neural connections, thus reducing depressive symptoms.

Both TMS and Spravato are FDA-approved and have shown amazing results in helping patients with TRD find relief. If you aren’t responding to antidepressants, talk to your doctor to see if TMS or Spravato could be the next step for you.

Final Thoughts

MDD and TRD are connected. MDD is depression, and TRD is depression that has not responded to typical treatments. Depression can feel overwhelming, but both MDD and TRD can be treated with the right support and plan.

If you are searching for the right place to get treatment for your depression, MDDCare can help you find clinics that provide trusted treatments for MDD and TRD. There are resources and providers that are ready to help you on your treatment journey. Visit MDDCare.com  today to take the first step and learn more about alternative treatment options like TMS and Spravato.