I started taking antidepressants about three years ago, but they haven’t worked well for me—at least, not yet. Trying different medications has felt like a roller coaster; at times I’ve felt empty and hollow, but there have been pockets of time where I’ve felt better than ever. Still, I haven’t found the exact right regimen yet. That’s because I have treatment-resistant depression (TRD), which isn’t a DSM diagnosis but is very much real.

Treatment-resistant depression is pretty much what it sounds like. “Treatment-resistant depression is a term used when the standard treatment protocols, such as talk therapy and medications, don’t relieve symptoms of depression,” explains Patrice N. Douglas, a therapist working toward her PsyD. “The symptoms are the same, but for various reasons, it may need a different approach to treatment.”

Experts usually classify depression as treatment-resistant when it doesn’t respond to traditional treatment plans, which may include medication or lifestyle changes. Carlene MacMillan, MD, CEO and founder of Brooklyn Minds Psychiatry, adds that the exact number of antidepressants varies depending on whose definition you are using but typically it is two or more antidepressants tried separately at an adequate dosage for several weeks. “The symptoms can be the same as ‘regular’ depression but the response to treatment is worse.”

Here, experts explain why depression can be resistant to treatment, how we might be able to manage it, and how to support someone going through it.

Why is depression resistant to treatment for some people?

Though there’s a cultural understanding of depression—a mood disorder that can cause feelings of apathy, sadness, hopelessness, sleep and appetite changes, and in some cases thoughts of self-harm—there isn’t a one-size-fits-all treatment that works for each person. What helps one person may do very little for another, says Douglas. “While medications are beneficial, it sometimes does take a process to find the right ones that suit the patient,” she says. That involves trying different medications, giving them time to assess efficacy and side effects—which is a difficult process, she notes. This can take months.

Talk therapy can be life-changing, but again, it sometimes isn’t the right solution for some people. “Talk therapy is the standard when we talk about mental health, but there are dozens of therapies that are beneficial and provide results in ways that talk therapy may not,” Douglas says. If talk therapy is not meeting someone’s needs, one can try art therapy, equine therapy, and dialectical behavioral therapy instead. Again, that takes time.

TRD can also occur because of an incorrect diagnosis—and therefore, the wrong meds. “Depression can look like many things, but often what isn’t considered is a medical condition causing the depression,” Douglas says. “It may be bipolar or another related disorder that needs a mood stabilizer instead of an antidepressant.” TRD is a relatively common occurrence in clinical practice, with up to 60% of patients not achieving adequate response following antidepressant treatment.

There’s also the fact that currently available medications, typically SSRI and SNRI antidepressants, work slowly and can only do so much. “There are different genetic factors at play that make some people’s depression more responsive to these medications than others,” says Dr. MacMillan. “Also, depression often does not exist in a vacuum. People who have other psychiatric disorders, like personality disorders or substance use disorders, may find their depression is more difficult to treat than those without other psychiatric concerns.”

Personal history and lifestyle factors, such as alcohol use and sleep hygiene, also can contribute to TRD. Just having depression can exacerbate problems with sleep, and so forth. “In my experience as a naturopathic physician, some people do not respond to conventional approaches if the root cause of the issue has not been addressed or if other underlying conditions have not been identified,” says JoAnn Yanez, ND, MPH, CAE, the executive director of the Association of Accredited Naturopathic Medical Colleges. “I have seen patients with unresolved trauma, hormonal issues, maladaptive stress coping, and life circumstances. When [those issues are] addressed appropriately, they do resolve fully or partially.”

What can you do for TRD?

While it can be hard to take care of oneself when feeling down, sleeping, eating and exercise are the foundation of feeling good, which can be part of an overall approach to treating depression along with therapy and medication. Dr. Yanez says, “Care should be taken to make sure you are eating a colorful, whole-foods based diet rich in omega fatty acids, protein and antioxidants.” Removing simple sugars/carbohydrates, caffeine and alcohol can also be helpful. Walking or more vigorous regular exercise has been demonstrated to assist in mood and blood sugar regulation. And while supplements like B vitamins, magnesium, neurotransmitter precursors, St. John’s Wort, lavender or chamomile can help some, patients should work with a licensed naturopathic doctor to find the treatment protocol that is best for them.

Beyond this, if you have treatment-resistant depression, it’s imperative to choose a care provider with experience helping people with TRD. For therapy, Fraga recommends psychodynamic or trauma-informed psychotherapy. “In some cases, the underpinnings of TRD are childhood or early trauma, and psychodynamic or trauma-informed therapy helps address this trauma,” she says.

If you take medication, Dr. MacMillan recommends looking for a psychiatrist who specializes in TRD and can offer treatments beyond the standard antidepressant pills. “For example, transcranial magnetic stimulation, esketamine (Spravato), MAOIs like the EMSAM patch, and even electroconvulsive therapy for extreme cases are all evidence-based, FDA-approved approaches for treatment resistant depression,” she says. There’s also OptionsMD, a service to help connect people with treatment-resistant depression to appropriate treatments and programs. You may also qualify for clinical trials for treatments like psilocybin, a psychedelic medicine, which can open up even more options.

Here, again, patience is necessary. “Sometimes it takes a while to get adjusted to medications and or therapy before you see improvement,” says Douglas. She also says to share your full medical history and your lifestyle routines with your treatment team, so that they can recommend the best treatment for you. On your own, Douglas recommends maintaining a mood journal to track how you are feeling daily—for the benefit of your treatment team and your own self. “You may not be able to tell that you are feeling better, but your mood journal may show progress, which can increase motivation.”

“People dealing with treatment resistant depression should look into the root cause of the depression for them,” says Dr. Yanez. “Naturopathic doctors recognize that depression is a symptom. [It’s] the body’s way of letting us know there is an imbalance somewhere.” She recommends people to check in on how they respond to stressors, and consider additional tools like mindfulness that can help with stress management.

Dr. Yanez says, “Natural therapies can be a powerful tool for some patients when under the guidance of a trained and licensed naturopathic doctor.” There are some fundamentals to helping our minds and bodies stay balanced. “Each one of these therapies may be helpful on their own or together. However, we encourage patients to work with a licensed naturopathic doctor, especially if they are also on pharmaceutical therapy, as some supplements are contraindicated with prescription drugs.”

How you can support someone with TRD

Social support is an important factor in helping people manage depression. It can take the form of coaches, a medical team, and professional counselors—but friends and family can also help their loved ones cope. “Depression is a medical illness and can be unpredictable and frustrating for all involved,” says Dr. MacMillan. “It should be treated the same way one would treat pneumonia or a broken leg and it is not a sign of weakness or moral failing.” As a loved one, your role isn’t to be a therapist, she says; sometimes the best thing you can do is help a person connect with treatment.

If someone you care about is struggling with depression, try to have patience, says Douglas. A person may have depression for months, even years—but that doesn’t mean they aren’t trying to get better. “Accept that they still may be struggling, even with treatment,” she says. Try to get involved with the treatment process; let them know they can talk about their medications with you, offer to drive them to therapy, and help them cook or grocery shop. “The more you are involved, the more you can help them stay on track. Be a team at all times,” she says. Friends and family of depressed people should know that they don’t have to go it alone, either. “The Depression and Bipolar Support Alliance and the National Alliance on Mental Illness have local and online chapters that offer support for loved ones,” says Dr. MacMillan.

I feel hopeful knowing I’m not alone in my experience of TRD and that there are paths possible for treatment. Although it may take time, which can feel utterly uncomfortable, I know I can—and will—get better.