Treatment-resistant depression (TRD) happens when at least two different antidepressants don’t improve your symptoms. Despite its name, there are several treatment options available, including medications and procedures like electroconvulsive therapy (ECT).
Treatment-resistant depression (TRD) is a type of major depressive disorder (MDD). It happens when at least two different first-line antidepressants aren’t enough to manage the condition during a depressive episode. The two treatments must be of adequate dosage and duration (at least six to eight weeks) before a healthcare provider can diagnose TRD.
First-line antidepressants for the treatment of MDD are usually SSRIs (selective serotonin reuptake inhibitors) or SNRIs (serotonin and norepinephrine reuptake inhibitors). This is because they generally have fewer and less severe side effects compared to other antidepressants. TRD can develop in people who were previously responsive to antidepressant medications.
Despite its name, there are treatment options available for TRD, but it may take time to find the right one for you.
Approximately 30% of people who’ve been diagnosed with MDD and who’ve tried medications for MDD have treatment-resistant depression. MDD is one of the most common mental health conditions. It affects 5% to 17% of people at some point in their lives.
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People with treatment-resistant depression (TRD) have the same symptoms as people with major depressive disorder, like depressed mood, sleep disturbances and appetite changes. But people with TRD are more likely to have:
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Researchers don’t know the exact cause of TRD. As depression has many contributing factors — like genetics and brain chemistry — so does treatment-resistant depression.
They think that chronic stress may contribute to TRD by changing the function of your hypothalamic-pituitary-adrenal (HPA) axis. Your HPA axis is an important bodily process that’s responsible for stress adaptation. Chronic stress can worsen depression, which makes it more difficult to treat.
Studies show that compared to people who have MDD that isn’t treatment-resistant, people with treatment-resistant depression are more likely to have physical health conditions, including:
The diagnosis of treatment-resistant depression isn’t clearly defined. But most healthcare providers diagnose TRD if your depression symptoms haven’t improved after trying at least two first-line antidepressant medications. Most providers consider the following to be first-line depression medications:
You generally have to take an antidepressant for at least six to eight weeks to see if it improves your symptoms.
If you don’t notice a change in your symptoms after trying two antidepressants, your healthcare provider may refer you to a psychiatrist. They’ll assess your medical and mental health history, including:
After this conversation, your provider may diagnose you with treatment-resistant depression. They’ll then work with you to find the best treatment option.
There are several strategies to manage treatment-resistant depression. It could take a while to find the right strategy for you. Try not to lose hope.
To start, your psychiatrist may:
If these strategies don’t work, your psychiatrist will likely recommend a different kind — or combination — of medications or treatments.
Currently, the U.S. Food and Drug Administration (FDA) approves five medications for the treatment of TRD:
The FDA has also approved the following treatments for TRD:
Other treatment options for TRD include:
Researchers are also studying psilocybin as a potential treatment for TRD. Psilocybin is a psychedelic compound isolated from hallucinogenic mushrooms.
Medications and treatments for TRD generally have more side effects than first-line antidepressants. And they can vary widely. Your healthcare provider will discuss the possible side effects or complications of each treatment option. Don’t hesitate to ask questions.
As scientists don’t know the exact cause of TRD, it’s generally unpreventable. But chronic stress likely plays a role, and there are steps you can take to manage your stress, including:
Aside from seeking professional, medical help for treatment-resistant depression (TRD), there are some things you can do at home that may help improve your symptoms, including:
You should have regular appointments with your healthcare provider while finding an effective treatment plan for TRD to assess how it’s working.
Otherwise, talk to your provider in the following situations:
A note from Cleveland Clinic
If you have treatment-resistant depression (TRD), know that you’re not alone. About 30% of people with major depressive disorder have it. There are several treatment options for TRD, but it’ll likely take time to find the best one for you. Your healthcare provider and/or psychiatrist will support you through the process.
Last reviewed by a Cleveland Clinic medical professional on 05/16/2023.
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