Strategies for Coping with Treatment-Resistant Depression (TRD)

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

I am a psychiatrist, specialist in child, adolescent and adult psychiatry. After my own personal experience with depression in my 20’s, I was on a lifelong quest to understand and help others.

I spent almost a decade at the National Institutes of Health looking for ways to predict which depression treatments might be most effective for different people. Today, I direct Washington Behavioral Medicine Associates, a group practice in Chevy Chase, MD, where we serve 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 TRD?

Most experts would agree that the definition of treatment-resistant depression is the failure of two or more antidepressant drugs, each prescribed and taken at maximum doses for at least 6 weeks.

What can you do if you have TRD?

There are many ways to successfully treat TRD. However, this does not mean that finding a successful treatment will be easy.

My approach to TRD is to offer support from multiple angles. I don’t just focus on medication for depression, but on an overall strategy that includes:

  • diet change
  • exercise
  • Medical examination with a comprehensive blood count
  • medication
  • neuromodulation
  • psychotherapy
  • Restful sleep
  • Dietary supplements and vitamins, especially when we identify a deficit

First, I find out about the details of previous treatments. It’s important for your doctor to understand how your symptoms have developed and how you have responded to previous treatments. Your doctor may ask what medications you’ve tried, the doses, how long you’ve been on them, and if you’ve had any side effects.

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

I can recommend supplements, vitamins and medicines to improve daily life. For example, vitamin D or omega-3 fatty acids can help improve mood. I also address the constant negative self-talk that comes with depression.

Finally, I’m looking for a combination of medication and neuromodulation to help your brain function more harmoniously.

What treatments are best for TRD?

Over the past 15 years we have had a welcome introduction of various evidence-based strategies to treat TRD. They include drugs and techniques that involve stimulating or inhibiting the brain, known as neuromodulation.

medication. For TRD, we go beyond classic depression medications such as Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin Norepinephrine Reuptake Inhibitors (SNRIs).

We can use medications such as tricyclic antidepressants, lithium, thyroid hormones and monoamine oxidase inhibitors (MAOIs). We can combine these with other medications such as atypical antipsychotics, buspirone or other mood stabilizers. The combination of possibilities is enormous.

Ketamine is an ancient anesthetic that has been shown to help relieve TRD within hours. This is in stark contrast to typical depression medications, which can last weeks. There has been some controversy surrounding 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 badly portrayed in movies and has fueled misinformation and suspicion, but it is a very safe and effective method of treating depression. ECT sends a small dose of electricity through your brain to change your brain chemistry and reverse your symptoms.

Another type is repetitive transcranial magnetic stimulation (rTMS). This is an FDA-approved treatment that uses a magnetic pulse delivered through a coil placed in your scalp. The pulse can stimulate or inhibit nerve cells in the part of your brain that affects mood control.

rTMS has minimal side effects and the results have been positive. It is my preferred method and I often combine it with other treatment strategies.

What other treatments might doctors try for TRD?

Light therapy is an established treatment option for people whose depression may be seasonal. If your mood takes a turn for the worse in the fall months, there may be a seasonal component to it.

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

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

Nitrous oxide (laughing gas) can help with depressive symptoms. It is fast acting and may resemble ketamine. But there is still no clear strategy on how to use N20 for depression. This could change in the near future as more research is now being done.

Does psychotherapy help TRD?

Psychotherapy is an important part of your treatment strategy.

In most cases, I prefer talking therapy strategies that focus on the here and now. Therapies that help you resolve problems, understand why you’re feeling stuck, promote a healthy mind-body connection, and help you recognize and manage emotions are often the most effective.

Depending on your situation, one form of therapy may be better than another. In many ways, I see different types of therapy through the same lens as different medications: some work better on one type of problem and some work better on others.

What are common challenges in treating TRD?

The first challenge is to make the right 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 we don’t yet have very good predictors for knowing whether we should choose one strategy over another, it’s a process of trial and error. This can be challenging and fuel anxiety and frustration.

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

Work with your family doctor and a therapist to try different strategies. It may be helpful to consult an experienced psychiatrist or psychopharmacologist.

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


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Strategies for Coping with Treatment-Resistant Depression (TRD)
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