Treatment-Resistant Depression

Conditions - Treatment-Resistant Depressionder

Treatment-resistant depression (TRD) occurs when you have an inadequate response to at least two antidepressants or treatments. TRD doesn’t mean that there isn’t a treatment that will work for your depression; it is just taking extra time to figure out the right treatment. 

About 1 in 3 adults with major depressive disorder (MDD) also have treatment-resistant depression in the United States. That is about 2.8 million individuals with TRD. As you can see, you are not alone with your treatment-resistant depression. 

For as many as two-thirds of individuals, the first antidepressant they try doesn’t help them. However, that doesn’t mean you should give up! Options MD utilizes over 200 treatment options to create a personalized treatment plan for you. 

Treatment-resistant depression can impact your mental and physical health and your ability to hold a job and function in everyday life.

Treatment-Resistant Depression

Treatment-resistant depression can be hard to define. 

Some experts define it as depression that hasn’t responded to two different antidepressants from different classes; others define it as depression that doesn’t respond to at least four different types of treatment. 

It is important to note that antidepressants are not designed to work immediately. It can take four to eight weeks to see the full effects of using an antidepressant, and even then, the dosage may need to be adjusted. 

Treatment-resistant depression is a diagnosis given to individuals who have already been diagnosed with another form of depression. To determine if your depression is treatment-resistant, your therapist or psychiatrist may ask you questions such as:

  • Have you been taking your medications? 
  • Have you been taking any other medications?
  • Do you have any other medical conditions that could be impacting your depression? 
  • Have there been any recent changes to your routine or environment? 
  • Are there any new stressors in your life?

These questions will help your care team determine if the origin of your resistance to treatment is biochemical, linked to another condition, or related to your environment. This can help your care team come up with a treatment plan.

Who is at Risk for Treatment-Resistant Depression

Some risk factors can make you more likely to develop TRD. 

  • Gender - Women seem to experience TRD at higher rates than men, which can be linked to biological and psychological reasons. 
  • Senior citizens - Older individuals seem to experience higher rates of TRD than their younger counterparts. 
  • Other conditions - Other conditions, such as an eating disorder, sleep disorder, or substance abuse issue, can make treating depression with antidepressants more complicated. 
  • Medical illnesses - Some medical diseases seem to be associated with a higher rate of TRD, such as chronic pain and thyroid disease. 
  • Early onset  - Early onset of depression can increase the risk of developing TRD. 

In addition, individuals who experience frequent and recurring depression episodes and who have long depression episodes can be at risk for TRD.

Treatment Options for Treatment-Resistant Depression

Is it possible to treat treatment-resistant depression? 

At Options MD, we have a team of psychiatric experts who have worked together to identify over 200 different depression treatment options.

If a previously-tried treatment option didn’t work, that just means it wasn’t the right treatment for your unique circumstances. Our team will work with you to develop a treatment plan that is right for you and work to refine it so you get the relief you need.


With treatment-resistant depression, it is important to consider all options. Numerous anti-depressants and medications may work for you. The key is to find the right medication and dosage. 

Some medication management options include 

  1. Switching antidepressants
  2. Trying a different class of antidepressants Trying two different classes of antidepressants at the same time
  3. Adding a medication that is not technically an antidepressant, but still has antidepressant effects.  (known as augmentation) 
  4. Increasing dosage

A wide range of different psychotherapy options can be used to treat depression. Finding the right psychotherapy approach for you may take a few tries, but many different approaches and delivery methods could work for you. 

  • Cognitive behavioral therapy
  • Acceptance and commitment to therapy
  • Interpersonal psychotherapy
  • Family and marital therapy
  • Group psychotherapy
  • Dialectical behavioral therapy

In addition to medication and psychotherapy, other procedures can be used to treat your depression. 

  • Ketamine - Ketamine is a schedule III non-narcotic that is used as a general anesthetic and has been approved now as a depression treatment option.  Two different forms of ketamine can be used for TRD. One form is delivered through an IV in low dosages, with the frequency of the dosages decreasing over time. The other is an FDA-approved intranasal form of Ketamine, called esketamine, administered at a physician’s office or clinic. 
  • Electroconvulsive therapy (ECT) - ECT delivers a small dose of electricity to your brain while you sleep to stimulate your brain cells and relieve major depression symptoms.
  • Vagus nerve stimulation (VNS) - This can be tried after other forms of brain stimulation have been tried. It delivers electrical impulses to your brain stem through the vagus nerve in your neck.
Lifestyle Changes

Sometimes, lifestyle changes can have an impact on your depression. These include changes such as 

  • Managing stress
  • Sleeping well
  • Improving sleep habits
  • Engaging in regular exercise
  • Eliminating alcohol or recreational drug use
  • Sticking to your treatment plan

Get the Help You Need for Treatment-Resistant Depression

Options MD can help you get the treatment you need! Our team of psychiatry experts has access to over 200 different science-backed, cutting-edge treatment options. We will work together to determine the most appropriate treatment option for you! 

We also started the largest community of people with severe and treatment-resistant depression. It is a safe, collaborative, and supportive place to learn about better medication options and leading-edge treatments. Join today to get access to qualified doctors and find friendship and support.

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