Do you feel like you have tried every possible treatment option for your major depressive disorder?

As if depression wasn’t insidious enough, allow us to introduce you to its fickle, evil twin: treatment-resistant depression (TRD). A major depressive disorder, as classified by the National Institute of Mental Health, TRD describes depression that has failed to respond to at least two different antidepressant treatments. Anyone who has needed to treat depression knows how hard it is to find an effective treatment but, unfortunately, treatment of TRD can be even more challenging when compared to other forms of depression. 

You might imagine that’s pretty rare, right? Wrong. Up to one-third of adults with major depression battle symptoms that don’t get better with treatment. Many people with depression struggle to find the medication that’s right for them, while others never respond to your standard antidepressants. According to Alexander Papp, MD, psychiatrist at UC San Diego Health, only 30-35 percent of patients respond to the first antidepressant they’re prescribed.

What Are The Signs And Symptoms Of Treatment-Resistant Depression?

The number one sign of TRD is that you’ve tried multiple antidepressants as directed (no skipping doses!) and still aren’t feeling better.

“If you haven’t had an adequate response to antidepressant medication by about 10 weeks of treatment with the optimal dose, it’s probably worthwhile to request a change in your treatment plan,” says John H. Krystal, MD, McNeil Professor and Chair of Psychiatry at Yale. “This change might involve adding psychotherapy, an additional medication, switching antidepressants, or starting a neurostimulation treatment.”

Pay attention to:

  • A lack of response to antidepressant medications and psychotherapy treatments (including cognitive behavioral therapy)
  • Depressive episodes increasing in severity and/or duration
  • Brief improvements followed by a return of depression symptoms
  • High anxiety or anxiety disorder

Okay, But How Do I Know It’s Treatment-Resistant Depression?

TRD is easy to misdiagnose for several reasons. Doctors prescribe the wrong dose, patients forget to pack their meds while they’re on vacation, or people simply get frustrated and quit taking their pills due to side effects, just to name a few. There are many scenarios that could cause someone to think an antidepressant isn’t working when it is (or could with minor adjustments).

“If depression isn’t treated correctly, it will look treatment-resistant,” says Papp. “In some cases, it’s the treatment that’s the problem, not the depression.”

So how do you know you’re really dealing with TRD?

  • You’ve figured out the right antidepressant and dosage. Unfortunately, there are no shortcuts here. While everyone’s personal threshold is different, most doctors recommend trying various classes of antidepressants (up to four) in order to find your perfect match. Typically, patients will start off with a selective serotonin reuptake inhibitor (SSRI)—such as Lexapro (escitalopram) or Zoloft (sertraline)—before moving to a selective serotonin and norepinephrine reuptake inhibitor (SNRI) like Cymbalta (duloxetine) and Effexor XR (venlafaxine). If neither does the job, it’s usually time for high level combination treatments. Keep in mind, each medicine takes six to eight weeks to work properly. That means up to eight months to accurately diagnose TRD.
  • Your other meds aren’t interfering. Even then, there are other reasons antidepressants might not work correctly. Papp points to additional medications as a common culprit. “Some medications—like blood pressure, antibiotics, or steroids—can speed up the enzymes that metabolize antidepressants too quickly,” he says.
  • You have a clean bill of health. Medical problems like hypothyroidism, chronic pain, hormone imbalances, and addiction can cause or worsen depression. If you’re not treating your depression’s underlying issues, then it’s sure to stick around no matter what medication you’re on.

Who Is At Risk?

A wide range of individuals are susceptible to TRD. Unsurprisingly, it follows many of the same patterns as depression:

  • People with previous episodes of depression
  • Senior citizens
  • Women
  • People with underlying medical conditions such as chronic pain, substance abuse, and sleep disorders

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