Learn / Rehab for Treatment-Resistant Depression (TRD)

Rehab for Treatment-Resistant Depression (TRD)

Hannah Friedman
 May 4th, 2022|   Clinically Reviewed by 
Rajnandini Rathod

Treatment-resistant depression (TRD) has the same symptoms as depression, but with a more complex and challenging recovery process. And those very symptoms can make it difficult to seek help.

Although the journey to recovery from treatment-resistant depression can feel daunting, there are a growing number of treatment options available. And the more you know about your diagnosis, the more easily you can manage your symptoms and get the care you need.

Defining Treatment-Resistant Depression
Although it’s similar to major depressive disorder in many ways, treatment-resistant depression has its own set of clinical characteristics.1 Specifically, TRD is defined as depression with symptoms that are not alleviated after trying 2 or more treatment options (medications) for at least 6 weeks each. Despite the myriad medical and behavioral options for treating depression, many people still struggle to find an effective treatment. ⅓ of people with major depression have TRD.2

If you think you may have this diagnosis, you’re likely already familiar with the symptoms of major depression.3 As stated by the American Psychiatric Association, the condition’s classic signs are as follows:

  • feeling sad or having a depressed mood
  • loss of interest or pleasure in activities once enjoyed
  • changes in appetite — weight loss or gain unrelated to dieting
  • trouble sleeping or sleeping too much
  • loss of energy or increased fatigue
  • increase in purposeless physical activity (e.g., inability to sit still, pacing, handwringing) or slowed movements or speech (these actions must be severe enough to be observable by others)
  • feeling worthless or guilty
  • difficulty thinking, concentrating or making decisions
    thoughts of death or suicide

If you’re thinking about suicide, get help right away. You can call the National Suicide Prevention Lifeline at 1-800-273-8255 to talk to someone, 24/7.

While these criteria are well understood, researchers are still exploring their underlying causes. Most people understand depression to be related to chemical factors in the brain. And research has confirmed that, even more than major depression, treatment-resistant depression has a genetic basis.1

Genetics aren’t the only cause of this illness. There are also a number of environmental factors that may contribute to depression4 —and it’s not just physical health. It has been associated with more frequent use of screens (cell phones, computers, etc.), and a lack of access to green space. High levels of air and noise pollution can also exacerbate symptoms. On the other hand, activities that guard against depression include confiding in other people, being part of a sports club or gym, and getting adequate sleep.

But there’s no quick fix for mental health. Even if you sleep for 8 hours a night and go to the gym every day, you may still experience depressive symptoms. And TRD can make you vulnerable to other conditions, like substance use disorders.

TRD and Substance Use Disorders

According to a 2019 study, patients with treatment-resistant depression are at a higher risk for developing addictions5 than those with more easily treated major depressive disorder. And the reverse is also true: patients with substance use disorders may be more susceptible to developing TRD,6 even after they seek help.

These findings have serious implications for the recovery process. If you have a history of either one of these conditions, you may be at risk of developing the other. And if you’re showing symptoms of both, you might want to consider treatment for co-occurring disorders.

Residential rehabs that offer this type of treatment may take a more nuanced approach. For example, you might work closely with your providers to develop an individualized plan of care. Depending on your exact program, you may have more or less say in which types of therapy you engage in during your stay.

Types of Therapy for Treatment-Resistant Depression

By definition, it’s challenging to find treatment for TRD. But remission is still possible. A growing body of research suggests that some therapies may be highly effective for patients with this diagnosis.


To be diagnosed with TRD, you must have tried at least 2 types of medication with little to no effect. Depending on which prescriptions you’ve taken so far, it may be worth continuing to experiment. For example, you might start by taking an SSRI (like Prozac) and then switch to a non-SSRI (like Wellbutrin). Some studies show that the act of switching medications may improve the symptoms of TRD.7

Ketamine Therapy

Ketamine therapy is an increasingly popular treatment for depressive disorders. A growing body of research supports the idea that ketamine may be especially effective for patients with treatment-resistant depression.8 This medication is normally administered in a controlled environment, facilitated by a psychotherapist and a medical team. During each session, you’ll receive an infusion of ketamine and enter a trance state, in which you may be able to process and accept difficult emotions. You’ll have time to talk about your experience afterward, either in a group or 1 on 1 with your therapist.

Transcranial Magnetic Stimulation (TMS)

Transcranial magnetic stimulation (TMS) is a comparatively new therapy for treatment-resistant depression.9 During a TMS session, a series of magnetic pulses are used to stimulate the brain. According to the American Psychiatric Association, “the procedure, which is noninvasive and painless, is conducted in the outpatient setting. Unlike electroconvulsive therapy (ECT), patients need no anesthesia or sedation.”

Studies show that TMS causes noticeable improvement in patients with treatment-resistant depression.10 Preliminary data suggest that this modality may be especially effective when combined with other approaches, like ongoing medications and psychotherapy.


Talk therapy, or psychotherapy, is a broad category. It includes modalities like cognitive behavioral therapy (CBT), dialectical behavior therapy (DBT), interpersonal psychotherapy, and more. Talk therapy is helpful for most mental health conditions, including treatment-resistant depression. However, different patients may benefit more from some specific types of therapy than others. Work with your provider to assess which format will best meet your needs.

Chris Aiken, MD, explains that talk therapy has “a slightly larger effect than pharmacotherapy” for patients with treatment-resistant depression.11 This modality offers patients ongoing support, and can dynamically respond to challenging situations in a way that medication just can’t. If you’re dealing with a sudden life change—like the loss of a job or relationship—you can easily schedule an extra session with your therapist. Changing or upping your medication is a much longer process.

Studies show that psychotherapy can amplify the effects of other TRD treatments,12 such as pharmacotherapy (the use of prescription meds). And although more research is needed in this area, most rehab programs already invite patients to engage in more than one therapeutic modality.

Combined Approaches to Recovery

Recovery is a complex process. During treatment, you’ll work closely with a team of providers to find the treatments that work best for you. Experts believe that a combined approach, including multiple modalities at once, is the most effective way to heal from TRD.13

Although treatment-resistant depression is a mental health condition, it can also impact your physical health, your relationships, and every other area of your life. Because of this, you may benefit from working with a variety of providers, such as a psychiatrist, a talk therapist, an art therapist, a medical doctor, and more. As you try various modalities, remember that there’s no single right answer. You might need to experiment with a few different combinations before finding the right fit.

How to Know When to Try a New Treatment

When you begin healing from any condition, whether it’s mental or physical, it’s important to track your symptoms carefully. For TRD, you can do this by journaling, using a mood tracker, or even making a spreadsheet to track how different behaviors affect your emotions. Working with healthcare providers is extremely important during this process. Your medical team—which may include an MD, therapist, psychiatrist, or other experts—will be able to refer to their notes, providing objective insight into your progress over time.

Trying New Medications

If you decide to try taking antidepressants for TRD,14 it’s absolutely essential that you follow your prescriber’s directions. Brain chemistry changes slowly, and it can be hard to know whether a new treatment is working unless you give it adequate time to take effect. Research suggests that it takes at least 4 to 6 weeks on a new medication before you start seeing results. That being said, everyone’s brain chemistry is different, and your experience here will be unique. Make sure to work closely with your provider to manage any side effects, and get their advice before changing or going off your meds.

Choosing the Right Therapist

When you’re working with an expert in any field, whether they’re a therapist or a plumber, it can take time to find the right fit. If you’ve been seeing a therapist for some time without noticeable results, don’t be afraid to look for a new provider. That being said, don’t jump ship just because it doesn’t feel good. The work of therapy may not be easy or fun; the question is whether it’s helping you make positive, sustainable changes in the rest of your life.

Environmental Factors

Because depression often has environmental causes, it can be helpful to see how your mood changes based on external factors. For example, do you feel worse in rainy weather, or when you don’t have time to see friends? In some cases, you can make behavioral changes to manage these symptoms, like investing in a sun lamp or rearranging your schedule. However, you’re unlikely to stop encountering common triggers. If life’s ongoing challenges have less of an effect on your mood as you continue treatment, it’s a sign that you’re on the right track.

Healing from TRD is an Opportunity

As painful as treatment-resistant depression can be, the process of healing can teach you a great deal. If you can, try to cultivate an attitude of curiosity about yourself and your healing journey. Doing this can help you commit to recovery, instead of being frustrated that you haven’t yet reached a certain goal.

When you try several different types of therapy, you’ll learn about yourself from every angle. People are complex, powerful, and multifaceted. That includes you. As you get to know yourself better, you may find that recovery is a creative act. For people with TRD, it means more than finding the right pill. Instead, this is the process of building a better and more fulfilling life.

With the proper support, you can absolutely heal from this condition. To connect with programs that offer treatment for TRD, you can browse our list of rehab centers here.

  1. Fabbri, C., Hagenaars, S. P., John, C., Williams, A. T., Shrine, N., Moles, L., Hanscombe, K. B., Serretti, A., Shepherd, D. J., Free, R. C., Wain, L. V., Tobin, M. D., & Lewis, C. M. (2021). Genetic and clinical characteristics of treatment-resistant depression using primary care records in two UK cohorts. Molecular Psychiatry, 26(7), 3363–3373. https://doi.org/10.1038/s41380-021-01062-9 [] []
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  8. New hope for treatment-resistant depression: Guessing right on ketamine. (n.d.). National Institute of Mental Health (NIMH). Retrieved from https://www.nimh.nih.gov/about/director/messages/2019/new-hope-for-treatment-resistant-depression-guessing-right-on-ketamine []
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