Strategies for managing treatment-resistant depression (TRD)

By Gonzalo Laje, MD, as told to Kara Mayer Robinson

I am a board certified psychiatrist in child, adolescent and adult psychiatry. After my personal experience with depression during my twenties, I have been on a constant quest to understand and help others.

I’ve spent nearly a decade at the National Institutes of Health researching ways to predict which depression treatments might be most effective for different people. Today, I run Washington Behavioral Medicine Associates, a group practice in Chevy Chase, MD, where we help patients of all ages with treatment-resistant depression, or TRD.

Here’s what you should know about TRD and advances in treatment.

How do you know it’s a TRD?

Most experts agree that the definition of treatment-resistant depression is the failure of two or more antidepressants, prescribed and followed at the maximum dose, for at least 6 weeks each.

What can you do if you have a TRD?

There are many options for successfully treating TRD. However, this does not mean that it will be easy to find a successful treatment.

My approach to TRD involves offering support from multiple angles. I’m not focusing just on depression medication, but on a comprehensive strategy that includes:

• Dietary changes
• Playing sports
• Medical evaluation with a comprehensive blood test
• medicine
• Neuromodulation
• Psychotherapy
• Refreshing sleep
• Supplements and vitamins, especially if we find a deficiency

First, I found out the details of the previous treatments. It is important for your doctor to understand how your symptoms have developed and how you have responded to previous treatments. Your doctor may ask about medications you’ve tried, the doses, how long you’ve used them, and whether you’ve had side effects.

Then I look at the broader medical picture. Could there be other factors at play? Do you have good sleep, diet and exercise habits?

I may recommend supplements, vitamins, and medications to improve daily living. For example, vitamin D or omega-3s may help improve mood. I also address the negative self-talk that comes with depression.

Finally, I am looking for a combination of medication and neuromodulation to help your brain work in a more coordinated way.

What are the best treatments for TRD?

In the past 15 years, we have had the welcome introduction of different evidence-based strategies for treating TRD. It involves drugs and methods that either stimulate or inhibit the brain, which is called neuromodulation.

medicine. For TRD, we go beyond traditional depression medications such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).

We may use medications such as tricyclic antidepressants, lithium, thyroxine, and monoamine oxidase inhibitors (MAOIs). We may combine these medications with other medications, such as atypical antipsychotics, buspirone, or other mood stabilizers. The mix of options is enormous.

Ketamine is an old narcotic drug that has been shown to help relieve TRD in a matter of hours. This is a significant difference from typical depression medications, which can take weeks to work. There has been some controversy about ketamine, but it offers hope for severe cases with limited options.

Neuromodulation. This is a treatment strategy that uses physical methods, such as electrical currents, to stimulate your brain.

One type is electroconvulsive therapy (ECT). It has been poorly portrayed in movies and has fueled misinformation and mistrust, but it is a very safe and effective way to treat depression. ECT sends a small dose of electricity through your brain to change brain chemistry and reverse symptoms.

What other treatments might doctors try for TRD?

Light therapy is a well-established treatment option for people whose depression may be seasonal. If your mood takes a turn for the fall months, it may have a seasonal component.

Light therapy can relieve symptoms, improve sleep, and increase energy. It depends on the device, but your doctor may recommend that you use light panels or goggles every morning for 20 to 30 minutes, starting in the fall.

Psilocybin, or “mushroom,” has been studied as a potential treatment for depression for many years. It is not clear if they are better than conventional antidepressants, but they may have fewer side effects. It might be an option if you’ve tried other things and it didn’t work. Talk to your doctor to see if it might be a good option for you.

Nitrous oxide (N2O), commonly known as “laughing gas,” may help treat symptoms of depression. It is fast acting and may be similar to ketamine. But there is no clear strategy yet for how to use N20 for depression. This may change in the near future as more research is being done now.

Does psychotherapy help TRD?

Psychotherapy is an important part of your treatment strategy.

In most cases, I prefer talk therapy strategies that focus on the present. Therapies that help you solve problems, understand why you feel helpless, promote a healthy mind-body connection, and help you recognize and deal with emotions are often the most effective.

Depending on your condition, one type of treatment may be better than another. In many ways, I think of the different types of treatment through the same lens as different medications: some work better for one type of problem and others work better for others.

What are the common challenges in TRD treatment?

The first challenge is getting the correct diagnosis. To find the best treatment, it’s important to understand other conditions you may have, such as anxiety, obsessive-compulsive disorder, personality disorder, or other medical problems.

Since there are not yet good predictors of whether we should choose one strategy over another, this is a process of trial and error. This can be difficult and can lead to anxiety and frustration.

What can you do to improve your chances of finding an effective treatment?

Work with your primary care provider and therapist to try different strategies. It may be helpful to consult an experienced psychiatrist or psychologist.

There are many treatment options. I’ve had many patients say, “I’ve tried them all,” “Nothing’s going to help,” or “You don’t know what it’s like.” But depression is a disease like any other. If your treatment doesn’t seem to be working, it may be time to discuss other strategies with your provider.