Treatment-resistant depression

Sometimes depression doesn't get better, even with treatment. Explore what you can do about it.

By Mayo Clinic Staff

If you've been treated for depression but your symptoms haven't improved, you may have treatment-resistant depression. Taking an antidepressant or going to psychological counseling (psychotherapy) eases depression symptoms for most people. But with treatment-resistant depression, standard treatments aren't enough. They may not help much at all, or your symptoms may improve, only to keep coming back.

If your primary care doctor prescribed antidepressants and your depression symptoms continue despite treatment, ask your doctor if he or she can recommend a health care provider who specializes in diagnosing and treating mental health conditions.

The psychiatrist reviews your medical history and may:

  • Ask about life situations that might be contributing to your depression
  • Consider your response to treatment, including medications, psychotherapy or other treatments you've tried
  • Review all of the medications you're taking, including nonprescription drugs and herbal supplements
  • Discuss whether you're taking your medications as prescribed and following other treatment steps
  • Consider physical health conditions that can sometimes cause or worsen depression, such as thyroid disorders, chronic pain or heart problems
  • Consider a diagnosis of another mental health condition, such as bipolar disorder, which can cause or worsen depression and may require different treatment; dysthymia, a mild but long-term (chronic) form of depression; or a personality disorder that contributes to the depression not getting better

Treatment-resistant depression symptoms can range from mild to severe and may require trying a number of approaches to identify what helps.

Medication strategies

If you've already tried an antidepressant and it didn't work, don't lose hope. You and your physician simply may not have found the right dose, medication or combination of medications that works for you. Here are some medication options that your doctor may discuss with you:

  • Give your current medications more time. Antidepressants and other medications for depression typically take four to eight weeks to become fully effective and for side effects to ease up. For some people, it takes even longer.
  • Increase your dose, if indicated. Because people respond to medications differently, you may benefit from a higher dose of medication than is usually prescribed. Ask your doctor whether this is an option for you — don't change your dose on your own as several factors are involved in determining the proper dose.
  • Switch antidepressants. For a number of people, the first antidepressant tried isn't effective. You may need to try several before you find one that works for you.
  • Add another type of antidepressant. Your doctor may prescribe two different classes of antidepressants at the same time. That way they'll affect a wider range of brain chemicals linked to mood. These chemicals are neurotransmitters that include dopamine, serotonin and norepinephrine.
  • Add a medication generally used for another condition. Your doctor may prescribe a medication that's generally used for another mental or physical health problem, along with an antidepressant. This approach, known as augmentation, may include antipsychotics, mood stabilizers, anti-anxiety medications, thyroid hormone or other drugs.
  • Consider pharmacogenetic testing. These tests check for specific genes that indicate how well your body can process (metabolize) a medication or how your depression might respond to a particular medication based on additional factors. Currently, pharmacogenetics tests are not a sure way to show if a medication will work for you, but these tests can provide important clues for treatment, particularly in people who have many side effects or have had poor results with certain medications. These tests are not always covered by insurance.

Psychological counseling

Psychological counseling (psychotherapy) by a psychiatrist, psychologist or other mental health professional can be very effective. For many people, psychotherapy combined with medication works best. It can help identify underlying concerns that may be adding to your depression. In working with your therapist, you can also learn specific behaviors and strategies to overcome your depression. For example, psychotherapy can help you:

  • Find better ways to cope with life's challenges
  • Deal with past emotional trauma
  • Manage relationships in a healthier way
  • Learn how to reduce the effects of stress in your life
  • Address substance use issues

If counseling doesn't seem helpful, talk to your psychotherapist about trying a different approach. Or consider seeing someone else. As with medications, it may take several tries to find a treatment that works. Psychotherapy for depression may include:

  • Cognitive behavioral therapy. This common type of counseling addresses thoughts, feelings and behaviors that affect your mood. It helps you identify and change distorted or negative thinking patterns and teaches you skills to respond to life's challenges in a positive way.
  • Acceptance and commitment therapy. A form of cognitive behavioral therapy, acceptance and commitment therapy helps you to engage in positive behaviors, even when you have negative thoughts and emotions. It's designed for treatment-resistant conditions.
  • Interpersonal psychotherapy. Interpersonal psychotherapy focuses on resolving relationship issues that may contribute to your depression.
  • Family or marital therapy. This type of therapy involves family members or your spouse or partner in counseling. Working out stress in your relationships can help with depression.
  • Dialectical behavioral therapy. This type of therapy helps you build acceptance strategies and problem-solving skills. This is useful for chronic suicidal thoughts or self-injury behaviors, which sometimes accompany treatment-resistant depression.
  • Group psychotherapy. This type of counseling involves a group of people who struggle with depression working together with a psychotherapist.
  • Mindfulness. Mindfulness involves paying attention and accepting one's thoughts and feelings without judging them as "right" or "wrong" in a given moment.
  • Behavioral activation. This type of treatment works with depressed individuals to gradually decrease their avoidance and isolation and increase their engagement in activities that they once enjoyed or activities that have been shown to improve mood.

Procedures to treat depression

If medications and psychotherapy aren't working, you may want to talk to a psychiatrist about additional treatment options:

  • Repetitive transcranial magnetic stimulation (rTMS). This type of treatment uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of depression. An electromagnetic coil is placed against your scalp near your forehead. The electromagnet used in rTMS creates electric currents that stimulate nerve cells in the region of your brain involved in mood control and depression. Typically, this treatment is delivered over 30-minute sessions in rapid bursts. This treatment can now be delivered over briefer sessions with dosing called intermittent theta burst stimulation.
  • Ketamine is a medication that's delivered through an IV in low doses. It's used for rapid relief of hard-to-treat depressive symptoms and its effects can last from days to weeks. Usually it's given in decreasing frequencies over several weeks. The FDA approved an intranasal form called esketamine that's given in a physician's office or a clinic under the supervision of a health care provider to monitor for possible serious side effects and because of the potential for abuse and misuse. Esketamine is for adults who have tried at least two other antidepressant medications that did not adequately control symptoms. Ketamine and esketamine work in the brain in a different way than standard antidepressants, and each is typically used along with an oral antidepressant.
  • Electroconvulsive therapy (ECT). While you're asleep, a carefully measured dose of electricity is passed through your brain, intentionally triggering a small, brief seizure. ECT seems to cause changes in brain chemistry that can relatively quickly reverse symptoms of major depression. Although there are potential side effects, such as temporary confusion or temporary memory loss, a series of ECT treatments may provide significant relief of severe depression.
  • Vagus nerve stimulation (VNS). Generally, VNS is only tried after other brain stimulation therapies such as ECT and rTMS have not been successful in improving symptoms of depression. VNS stimulates the vagus nerve with electrical impulses. This treatment uses a device implanted in your chest that's connected by a wire to a nerve in your neck (vagus nerve). Electrical signals from the implant travel along the vagus nerve to the mood centers of the brain, which may improve depression symptoms.

Be sure to find out whether your insurance covers any treatment that's recommended.

Other steps you can take

To make the most of depression treatment:

  • Stick to your treatment plan. Don't skip therapy sessions or appointments. It'll take time to get better. Even if you feel well, don't skip your medications. If you stop, depression symptoms may come back, and you could experience withdrawal-like symptoms. If side effects or drug costs are a problem, talk with your doctor and pharmacist to discuss options.
  • Stop drinking or using recreational drugs. Many people with depression drink too much alcohol or use recreational drugs or marijuana. In the long run, alcohol and drugs worsen depression and make it harder to treat. If you can't stop drinking alcohol or using drugs on your own, talk to your doctor or mental health professional. Depression treatment may be unsuccessful until you address your substance use.
  • Manage stress. Relationship issues, financial problems, an unhappy work life and many other issues can all contribute to stress, which in turn worsens depression. Try stress-reduction techniques such as yoga, tai chi, meditation, mindfulness, progressive muscle relaxation or writing your thoughts in a journal.
  • Sleep well. Poor sleep may worsen depression. Both the amount of time and how well you sleep can affect your mood, energy level, ability to concentrate and resilience to stress. If you have trouble sleeping, research ways to improve your sleep habits or ask your doctor or mental health professional for advice.
  • Get regular exercise. Exercise has a direct effect on mood. Even physical activity such as gardening or walking can reduce stress, improve sleep and ease depression symptoms.

Don't settle for a treatment that's partially effective at relieving your depression or one that works but causes intolerable side effects. Work with your doctor or other mental health professional to find the best treatment possible, even though it may take time and effort to try new approaches.

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April 10, 2021 See more In-depth

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