Understanding Treatment-Resistant Depression

Don’t give up if your depression treatment isn’t helping you feel better. A change in your medication or a new approach might be the answer you need. Here are some of the many options.

By Beth W. Orenstein
Medically reviewed by Cynthia Haines, MD

understanding treatment-resistant depression
Though you may be faithfully following your depression treatment plan, you might not feel that sense of despair lifting. If some of your depression symptoms are lingering, you could have what’s called treatment-resistant depression.

About two-thirds of people with severe depression find that the first antidepressant they’re given doesn’t work, and as many as one-third still suffer from depression symptoms after trying several different depression treatments.

The definition of treatment-resistant depression is open to debate. “Some define it as a person who fails one antidepressant trial, but more commonly, treatment-resistant depression is defined as failing two different antidepressants from two different classes,” says Adam Lowy, MD, a psychiatrist at the Psychiatric Institute of Washington in Washington, D.C. In this case, “failing” simply means that a person isn’t helped by a particular medication. The good news is there’s a wide variety of antidepressant medication available today “and once the right one is found, antidepressants should be able to treat most people with depression.”

Learning to Be Patient With Depression Treatment

Don’t jump to the conclusion that your depression treatment isn’t making you better without giving it enough time. “Everyone wants to get better quickly, and if you’re not seeing improvement after two or three weeks, you can sometimes be inappropriately labeled as a ‘nonresponder,’” Dr. Lowy says. That’s because you really should wait at least six to eight weeks before you or your doctor decides that a particular medication isn’t working.

It’s also important to share pertinent information. Before you are considered treatment-resistant, your doctor might ask:

Are there any life events that could be contributing to your being depressed?
Are you taking your medications exactly as prescribed?
Are you experiencing side effects and taking your drugs less often as a result?
Do you have symptoms of any other mental health conditions, such as bipolar disorder or schizophrenia?
Are you experiencing any other health issues, such as heart problems, anemia, or pain, that could be causing you to become depressed? Are you taking medications for any of these conditions?
Your answers can help your doctor determine whether you have treatment-resistant depression or if something else is causing you to still feel acutely sad while taking an antidepressant.

Other Depression Treatments Available to You

What if you do have treatment-resistant depression? If your depression treatment isn’t working or isn’t working as well as you would like, don’t give up. You have options, such as:

Trying a different medication. A different drug may work more effectively for you. One category of antidepressants is selective serotonin reuptake inhibitors, or SSRIs; another is serotonin and norepinephrine reuptake inhibitors, or SNRIs; and a third is monoamine oxidase inhibitors, or MAOIs. “There is little evidence that any one of the SSRIs is better than any of the others,” Lowy says. But some people find they can tolerate one better than another. Therefore, your doctor might suggest switching from one antidepressant to another in the same class or to an antidepressant in a different class.
Adjusting your dosage. In cases of severe depression, a person may need to increase their dosage to the highest safe amount before deciding it’s not effective.
Taking an add-on medication. Your doctor might suggest you try a combination of drugs, possibly from two different classes of antidepressants or an antidepressant and a medication that is used secondarily to treat symptoms of depression. Lowy says, among others, some schizophrenia and bipolar disorder drugs are sometimes given as add-ons for depression.
Other options for treatment-resistant depression include:

Counseling. Just as there are different drug options, there are different talk therapies you can try, including cognitive behavioral therapy, or CBT, a style that’s been shown to be effective for depression. CBT encourages you to see how your thoughts and behaviors can contribute to your depression and helps you change them. You might try one-on-one talk therapy or group therapy.
Support groups. You may feel less alone and more encouraged if you talk with other people who are dealing with depression as well. Find a support group online or look to local hospitals for in-person groups near where you live.
Neurostimulation. Stimulating the mood centers of the brain is another option used in certain cases of treatment-resistant depression. Types include:
Electroconvulsive therapy (ECT). ECT uses electric impulses to induce a brief seizure. Given while you are under sedation, it is an incredibly effective treatment for severe depression, Lowy says, although there’s a stigma attached to it due to side effects it caused before general anesthesia was introduced. The more people speak out about ECT as an effective treatment, the more these misconceptions can be eliminated. Lowry notes that on the current Showtime series Homeland, the character Carrie voluntarily undergoes ECT for her bipolar disorder. “Maybe that media exposure will help take some of the stigma away,” he says. Still, the procedure’s potential side effects are riskier than more conventional therapies used for depression today and ECT is only considered an option for those who can’t take medications or for whom medications alone don’t work.
Vagus nerve stimulation (VNS). The vagus nerve stretches from the brain to the belly. Like ECT, this therapy uses electrical current to stimulate the brain. VNS is a serious surgery that requires that a device be implanted in your chest to send the impulses. Studies are still ongoing to determine its level of effectiveness.
Transcranial magnetic stimulation (TMS). This treatment uses magnetic coils to stimulate the areas of the brain that control mood. TMS is a relatively new treatment for depression and may be best for moderate cases.
Also, don’t neglect the importance of healthy habits: Making lifestyle changes can help treat depression. Be sure to eat a healthy diet, get regular exercise, foster your relationships, and get quality sleep.

Finding Depression Treatment That Works

Everybody is different — what works for one person’s depression may or may not work for you. It may take some trial and error. It also may take some time for the therapies to work. But if you’re patient and work closely with your doctor, together you can find effective treatments for your depression.