July 5, 2022/Mental Health

Treatment-Resistant Depression: What We Know and How To Manage It

If you’ve gone through two courses of medications, you may have this kind of depression

Illustration of a woman hugging herself beneath a dark cloud of black hair that represents treatment-resistant depression.

If you’re living with depression, you know that it can be difficult to take the first step toward treatment. But what if you’re taking the steps to help yourself and that dark cloud still continues to linger?


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At a certain point, a psychiatrist may diagnose you with treatment-resistant depression (also known as refractory depression) — a type of depression that continues to resist any commonly used therapies or medications you throw at it. If you’re struggling with this kind of depression, you’re certainly not alone. One-third of people with depression experience this kind of persistent depression.

Psychotherapist Anne Posey, LMHC, explains what we know about treatment-resistant depression so far and options for coping.

What is treatment-resistant depression?

Keep in mind, “treatment-resistant” does not mean “untreatable.”

Treatment-resistant depression is generally defined as a type of depression that doesn’t respond to treatment after a certain amount of time. Specifically, this is when a person doesn’t have a significant improvement after two courses of different antidepressants. According to Posey, a course of antidepressants would be prescribed for at least six weeks before deciding they aren’t effective.

This doesn’t mean that it can’t be helped over time through other techniques.

How to recognize the signs of treatment-resistant depression

You may be wondering: “How do I know if I have depression or treatment-resistant depression?” The truth is, the best way to untangle this answer is by working together with your psychiatrist and healthcare team to help understand your medical history.

“Depression itself is more than just having a bad day,” says Posey. “It’s when you feel depressed every day, almost all day for a period of longer than two weeks.” But then treatment-resistant depression, you’ll see a combination of different effects on your routine and response to medications.

Signs of treatment-resistant depression can include:

  • You’re not improving with antidepressants. This is the big one. While it’s common for people with depression to have to try different medications, if you’ve gone through two full courses of medications and you’re still not improving, this is a crucial sign of treatment-resistant depression.
  • Brief improvements. This may sound surprising, but if you feel a slight improvement in your depression followed by a swift return of those symptoms, it could be a sign that your treatment isn’t working.
  • Sleep disturbance. We don’t just mean jolting awake in the middle of the night or waking up feeling fatigued. Posey explains that another sign is waking up unusually early — often referred to as “early morning awakening” — and you can’t go back to sleep.
  • Changes in appetite. Changes in eating habits are common for this kind of persistent depression. Look for signs like skipping meals and losing your appetite for things you usually like for long periods of time.
  • Thoughts of suicide or self-harm. Suicidal thoughts are another common symptom of severe depression — and if it’s not getting better with medications, take note of this with your psychiatrist or healthcare team. If you or a loved one has experienced suicidal ideations or thoughts of self-harm, know that there are other resources available such as the 988 Suicide & Crisis Lifeline.

How is treatment-resistant depression diagnosed?

The diagnosis of different types of depression isn’t all black and white. But there are certain things we’re continuing to learn. If you’ve noticed signs of treatment-resistant depression in yourself and want to pursue a diagnosis, your therapist and psychiatrist will want to take different factors into consideration.

To determine if you have treatment-resistant depression, you may be asked:

  • Have you been taking your medications?
  • Have you started taking other medications?
  • Has your environment or routine changed recently?
  • Are there new stressors in your life?
  • Are there any other conditions that could be affecting these symptoms?

“This is going to help us answer the questions like, ‘Is this biochemical? Or could this be a product of what’s going on in your environment?’ Or maybe it’s both,” says Posey.


It’s also important for your healthcare providers to get a concrete timeline for your treatment. This will help them determine if your medication or therapy is helping or not. Plus — don’t try switching your medications too soon — many of the first-line antidepressants take several weeks before you notice any effects.

Is it treatment-resistant depression or something else?

In some cases, treatment-resistant depression can be a mask worn by a different culprit. If it turns out you have a different condition completely, antidepressants will be less effective in relieving these symptoms. That’s why talking to your psychiatrist and healthcare provider is important so they can identify the cause and appropriate treatment.

“Your doctor will want to get a good health history from you,” says Posey. “It may be determined that what we are actually dealing with isn’t depression, maybe it’s bipolar disorder.”

They’ll also want to take into consideration any other mental health conditions you may have — like anxiety — to make sure the medications aren’t interfering with each other.

How is treatment-resistant depression treated?

Depending on your diagnosis and your previous antidepressants, your psychiatrist may change your medication or introduce a new type of therapy to see how you do.

Posey says initial recommendations may include:

  • Switching to another type of antidepressant.
  • Joining group therapy or a new form of counseling.
  • Using workbooks or activity books to track your mood.

“Another holistic approach could be avoiding things that can make depression worse, such as using substances like alcohol,” says Posey.


Procedures for treatment-resistant depression

If a change in therapy, antidepressants or lifestyle still aren’t helping, there are still other ways to manage treatment-resistant depression.

Other treatment methods that are available for people with treatment-resistant depression include:

  • Electroconvulsive therapy (ECT). Despite how it’s shown in movies and TV shows, ECT has become a reputable form of treatment for depression that may help with improving severe cases. “We all have that One Flew Over the Cuckoo’s Nest idea about what it is but, it’s actually not like that anymore,” Posey reassures. It involves general anesthesia and has shown a high success rate over the years. “It’s a very controlled type of treatment and it can be very effective for people with treatment-resistant depression.”
  • Transcranial magnetic stimulation (TMS). This is another treatment option that shows promise for people with persistent depression. TMS is usually administered in 30 sessions over four to six weeks. “It uses magnetic waves to disrupt the brain chemistry and try and reset it,” says Posey.
  • Ketamine.While it doesn’t work for everyone, some studies show that ketamine can improve clinical symptoms of treatment-resistant depression when administered through an IV in small doses. There’s even a nasal spray option that’s available, too.
  • Deep brain stimulation (DBS).Used mostly for conditions like Parkinson’s disease, this treatment involves an implanted device that sends an electrical current to parts of your brain. While it’s less common, it’s shown promise for severe types of depression.

The important thing to remember is that there are options out there. However, these therapies and procedures should only be considered after your psychiatrist has given enough time for antidepressants to work.

How do I practice self-care when I have treatment-resistant depression?

If your depression doesn’t respond to treatments, it can be hard to know how to find relief. Switching medications and different therapies can be jarring, so it’s important to find ways to keep yourself grounded.

Alongside your therapy and medications, you can also find ways to take tiny steps in your personal life like:

  • Find support systems. As you go through treatment changes, you’ll want to have a supportive community around you. While it’s easy to shut yourself away, seek out the people in your life who will help validate what you’re going through. “Our support systems are really important to make sure that we recognize that we have a chronic illness and that it takes time to treat it,” says Posey.
  • Setting a routine. Consistency during your day-to-day life can be healing in itself. While it won’t fix all of your problems, having a set time to get up and go to bed will help your body get in a better rhythm as you’re trying different treatments and therapies.
  • Exercising. Even if it’s a walk around the block, finding time to move your body can be a holistic way to help your mood while battling depression.

How to know if you’re finally improving

It’s important to also know the signs that indicate you’re heading in the right direction. Healing from treatment-resistant depression can be a slow process for many, but it’s important to take note of small improvements.

“As someone improves, we would want to see their sleep stabilize, and maybe their appetite and energy increase,” Posey explains. “Or they’re having the ability to get up and do the things that they enjoy doing.”

Whatever treatment or therapy option you choose, treatment-resistant depression affects every person a little differently. So, it’s important to take note of how your mental health is changing and how it may require new solutions. Talk to your psychiatrist or healthcare provider to learn more about the best treatment options for you.

If you or someone you know needs help, reach out to a mental health expert or connect with a resource or support group, such as:

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