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While antidepressants work well for many people, they don’t improve symptoms for roughly 15 percent of those living with depression. Getty Images
  • Over 17 million U.S. adults will experience a major depressive episode in any given year.
  • A third of adults dealing with major depressive disorder are estimated to be living with treatment resistant depression.
  • This is a form of depression that doesn’t respond to antidepressants.
  • Alternative treatments have been found to be effective. These include psychotherapy, electroconvulsive therapy, cognitive behavioral therapy, biofeedback, exercise, meditation, acupuncture, and ketamine infusions.

At 43 years old, Sara* has been dealing with depression for 2 decades. Over the years, she told Healthline she’s been prescribed many different medications.

None of them have ever worked for her.

“It’s been a roller coaster of medication adjustments and medication changes and medication combinations and medication attempts. It’s been a very long, hard road with medications,” she said.

A few years ago, she was finally diagnosed with treatment resistant depression (TRD), a condition that impacts as many as one-third of adults dealing with major depressive disorder.

In the United States alone, 17.3 million adults experienced a major depressive episode in just 2017.

That’s a little over 7 percent of the population.

Then you have those who may experience persistent depressive disorder (1.5 percent of U.S adults), bipolar disorder (2.8 percent), or postpartum depression (10 to 15 percent of women).

But while depression isn’t uncommon, for those who are experiencing the symptoms, they can often feel as if they’re all alone.

For many, even taking that first step of calling a doctor and admitting they need help can be overwhelming.

But what happens when you take that step and the medications you’re offered don’t help?

When a person is struggling with depression, there are several classes of antidepressants available.

“Each class targets different neurotransmitters,” clinical psychologist Carla Marie Manly, PhD, told Healthline.

She explained that the 4 most common classes include:

MAOIs, Manly explained, are prescribed less frequently than the other classes of medications.

“In most cases, 4 to 6 weeks on a therapeutic dose of an antidepressant is enough time to assess if the medication is working,” said Dr. Alex Dimitriu, who is double board certified in psychiatry and sleep medicine.

He made a point of explaining that’s only for therapeutic doses, though.

“Indeed, most doctors will appropriately start with lower doses to minimize side effects. But these doses may not be effective, and hence not count toward the 4–6 week time period to assess full response,” he said.

He also pointed out that some evidence suggests anxiety disorders may take even longer for medications to become effective.

In a perfect world, the first medication a person tries would work to end their depression.

When that happens, “whatever symptoms of depression they presented with should resolve,” said Dr. Mary Beth Lardizabal, DO, medical director of child and adolescent psychiatry at Allina Health in Minneapolis, Minnesota.

“What I always say is getting back to their regular life is a sign that it’s working,” she added.

Dimitriu agreed, adding, “When antidepressants work, patients chiefly report improved mood and energy and reduced anxiety. They will feel more motivated, less sad most of the time, and more interested in pleasurable activities.”

However, for those like Sara who are living with TRD, getting effective treatment isn’t as easy.

TRD is “quite common,” according to Lardizabal.

“Twenty to thirty percent of people don’t respond to their first medication trial, and then you have the second and possibly a third. And there are some people [for whom] the antidepressant effect starts to lose effect over time.”

When that happens, she said people have to switch to different drugs, or change dosing.

“Sometimes you’ll max out the dosing, so you’ll need to try something else. That’s when you talk about augmentation strategies, adding something else. Some people just don’t seem to respond to any medication,” she added.

When Sara found this was the case for her, she battled against an onslaught of negative feelings as a result.

“It made me feel frightened, angry, sad, hopeless… and so much more,” she said.

One of the things all the experts Healthline spoke to made clear is that there are other options when medications fail to treat depression.

“When medications are not effective, alternative treatments including psychotherapy are available,” Manly explained.

“Cognitive behavioral therapy (CBT) is generally quite effective for depression,” she said. “As well, other alternative treatments such as biofeedback, exercise, meditation, acupuncture, and dietary supplements have proven to be effective in many cases.”

Lardizabal agreed, pointing out that CBT “has the most evidence about treating major depressive disorder [so] doctors first line of treatments should be getting the patient a good therapist, preferably one who practices cognitive behavioral therapy.”

She also pointed out that while electroconvulsive therapy has had a bad image in the past, “It’s much different now than it was back then.”

She explained it can be quite effective for those struggling with TRD.

Today, Sara said she finally feels like she’s on the right track with treating her depression.

“Finding my current psychiatrist was huge,” she said enthusiastically.

Sara said her psychiatrist began administering ketamine infusions to treat her depression symptoms which has had some success.

“The combo of him and the infusions saved my life,” she said.

In addition to that, she says her current therapist is a very positive aspect of her treatment plan.

One of the biggest things she said has helped was stopping a medication she’d been taking for insomnia. “I now know it was making my depression a trillion times worse,” she said.

Still, she’s cautious to overstate her progress today.

“I’m still very much fighting, searching, and digging for what will ultimately ‘work.’ But it’s not just one thing… it’s a bunch of things working together that has to take place and finding the right combo is hard.”

For anyone struggling to find that combination themselves, Sara advised, “Get a good psychiatrist. Not a primary care doctor who just writes a prescription for an antidepressant. I can’t stress this enough. Get a good psychiatrist.”

She added, “Find a psychiatrist who will fight for you. Find a psychiatrist who has their hand in research and has many tools in their tool belt for treating depression and other mental health disorders.”

A must for the right psychiatrist, she added, is empathy.

“If they are not empathetic, compassionate, or motivated to fight for you, move on and go to the next,” she said.

*Name changed to protect privacy