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Treatment-Resistant Depression: How to Manage

Mary Lucas, RN

Medically reviewed by Mary Lucas, MSCIS, MPhil, RN

Written by Our Editorial Team

Last updated 12/22/2021

Depression is a common form of mental illness that affects tens of millions of American adults every year. 

Most people with depression experience improvements with depression treatment options such as therapy and medication. 

However, some people with depression have persistent symptoms that simply don’t respond to conventional forms of treatment.

When major depression doesn’t improve with antidepressants or therapy, it’s generally referred to as treatment-resistant depression. 

Treatment-resistant depression can be challenging to deal with, but it’s often manageable with specialized forms of therapy, changes to your use of medication and specific treatments, such as electroconvulsive therapy.

Below, we’ve listed the symptoms you may experience if you have this form of depression, as well as the options that are available for reducing the severity of your symptoms and improving your quality of life. 

Symptoms of Treatment-Resistant Depression

Treatment-resistant depression typically involves the same symptoms as clinical depression, or major depressive disorder. 

If you’re depressed, you may experience the following symptoms on a daily or near-daily basis for a period of two weeks or longer:

  • Persistent feelings of sadness, emptiness or anxiety

  • Negative beliefs, such as that things are hopeless

  • A lack of interest in your hobbies, passions and interests

  • Feelings of worthlessness, guilt or that you can’t be helped

  • Difficulty remembering information or focusing on specific tasks

  • Changes in your sleep habits or ability to fall asleep normally

  • A reduced ability to make decisions

  • Slowed speech and/or movement

  • Fatigue and a feeling of reduced energy

  • Changes in your appetite and weight gain or loss

  • Irritability and a general shorter temper

  • Pain, discomfort and digestive problems without a clear reason

  • Suicidal thoughts and/or behavior

Even if you’re depressed, you may not experience all of the symptoms listed above. In some cases, you may experience depression symptoms that come and go from day to day, or mild symptoms that become more severe in certain situations. 

For most people with depression, these symptoms gradually improve with therapy and/or the use of antidepressants. 

However, if you have treatment-resistant depression, you may notice little or no change in the severity of your symptoms, even with ongoing treatment. In some cases, your symptoms may get better only to come back in the future, despite ongoing treatment. 

What Causes Treatment-Resistant Depression?

A variety of factors may all play a role in the development of depression, including your genes, levels of certain naturally-occurring chemicals, life experiences and general health.

We’ve talked about these, and the different ways in which they may contribute to depression, in our guide to the causes of depression.

When it comes to treatment-resistant depression, experts haven’t identified a single issue that’s solely responsible. 

However, several factors have been identified that may contribute to an elevated risk of developing treatment-resistant depression. These include:

  • Your genes. Some genes may affect the synthesis of tryptophan in your body, an amino acid that’s used to produce serotonin (an important chemical in our brains that regulates our mood and feeling of well-being). An imbalance in the chemical levels in your brain may result in reduced effects from conventional depression treatments. 

  • Not using antidepressants properly. You may be more likely to develop persistent or treatment-resistant depression if you skip doses of antidepressants or stop taking your medication for any reason.You may also experience reduced improvements if you stop taking antidepressants too soon, as many medications require several weeks to start working properly.

  • Using the wrong antidepressants. Sometimes, using the wrong type of medication can prolong your depression. Even using the correct medication at a low dose may result in few or no improvements.

  • Medical conditions. Some medical conditions, such as heart disease, cancer, or certain psychiatric disorders can contribute to depression and may need to be treated to prevent your depression from worsening or not improving on therapy. 

How to Manage Treatment-Resistant Depression

If you think that you might have treatment-resistant depression, it’s important to reach out to a mental health provider for assistance.

In order to learn more about your depression, your mental health provider may ask about your symptoms and mental health history, the medications you currently use or have recently used for depression and your general life situation. 

They may also ask you about any physical or mental health conditions you have that could play a role in your depression. 

Depending on the type and severity of your symptoms, your treatment history and other factors, your mental health provider may recommend one or several of the treatment approaches listed below. 

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Make Changes to the Way You Use Your Medication

Depression is commonly treated using antidepressants — medications that change the levels of certain chemicals, called neurotransmitters, in your brain. 

Although antidepressants tend to be effective, they often need some adjustments before they work best. 

If you have depression and don’t seem to experience any improvements from the antidepressants you’re taking, your mental health provider may suggest making one or more changes to the way that you use your medication, such as the following:

  • Give your current antidepressant extra time. Antidepressants are usually effective at reducing the severity of depression, but they don’t work immediately. It can take two to four weeks for antidepressants to start working, and they often improve sleep and appetite before mood. If you’ve only used your medication for a few weeks, it might be best to give it more time before you make any changes to your routine.

  • Increase your antidepressant dosage. The dosage requirements for antidepressants can vary based on your age, weight, sex, physical health and even the severity of your depression symptoms.If you’ve used antidepressants for several weeks but haven’t seen any improvements in your symptoms, your healthcare provider may suggest increasing your dosage.

  • Switch to a different type of antidepressant. Depression is usually treated with newer antidepressants, such as selective serotonin reuptake inhibitors (SSRIs). If these fail to treat your symptoms, you may need to switch to a different type of antidepressant. Other antidepressants used to manage treatment-resistant depression include tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs).

  • Use more than one type of medication. Sometimes, the most effective way to manage treatment-resistant depression is to add a second medication. This form of treatment is often referred to as augmentation therapy.

  • Add other medications. Depression also often improves with the addition of other types of medication, such as thyroid hormone, stimulants, mood stabilizers, sex hormones and antipsychotic medications.

It’s important to closely follow your healthcare provider’s instructions and use medication only as directed. 

Don’t make any changes to your dosage or the type of antidepressant you use without first talking to your healthcare provider. 

Antidepressants can cause adverse effects. Make sure to inform your healthcare provider if you experience any severe or persistent side effects while using medication for depression. 

Explore Other Forms of Therapy

Many people with depression benefit from psychotherapy, or talk therapy. 

In fact, research has found that a combination of psychotherapy and antidepressants is more effective at treating the symptoms of depression than medication alone.

Therapy for depression often involves identifying distorted thought processes, changing the way that you think and behave and learning new skills for coping with your symptoms.

If your depression is persistent or simply doesn’t improve, your mental health provider may look into different types of psychotherapy. These may include:

  • Cognitive behavioral therapy (CBT). This type of therapy involves identifying faulty or unhelpful ways of thinking that can contribute to your depressive symptoms. You’ll learn how to change these thought patterns to improve your feelings and behavior.

  • Interpersonal therapy (IPT). Interpersonal therapy is a structured and time-limited form of therapy that involves identifying and solving interpersonal relationship issues that are affecting your thinking and behavior.

  • Acceptance and commitment therapy (ACT). Acceptance and commitment therapy involves accepting issues and setbacks in life and using positive behavior to move on during challenging periods.

  • Dialectical behavioral therapy (DBT). Dialectical behavioral therapy is often used to treat borderline personality disorder (BPD). It combines therapy with problem-solving skill development.

  • Behavioral activation. Behavioral activation involves reducing isolation and gradually re-engaging with life. It’s intended to help people engage in activities they enjoy while avoiding the inactivity and withdrawal that can worsen depression. 

  • Mindfulness-based cognitive therapy (MBCT). Mindfulness-based cognitive therapy combines cognitive behavioral therapy with mindfulness-based techniques for reducing stress. It’s generally used to treat depression and anxiety disorders.

Just like with antidepressants, you may need to try several forms of therapy before finding one that works well for you. 

Make sure to inform your mental health provider if you feel like a certain form of treatment doesn’t feel effective. 

Try Specialized Procedures for Depression

If antidepressants and conventional forms of therapy aren’t effective at treating your depression, your mental health provider may recommend a specific type of procedure to reduce the severity of your symptoms. 

These procedures are often referred to as brain stimulation therapy. 

They typically involve using therapeutic equipment to stimulate the regions of your brain that are involved in regulating your thoughts, moods and feelings. 

Medical procedures for depression include:

  • Electroconvulsive therapy (ECT). This form of treatment involves passing a controlled electrical current through your brain. It’s used to treat severe depression, bipolar disorder and other mental disorders, such as schizophrenia. ECT takes place under general anesthesia, meaning you’ll be asleep as the procedure is performed. This type of treatment may need to be repeated for several weeks to produce lasting improvements. 

  • Repetitive transcranial magnetic stimulation (rTMS). This type of treatment activates your brain using a magnetic field. It’s performed without anesthesia, with most sessions lasting for 30 to 60 minutes. 

  • Vagus nerve stimulation (VNS). This form of treatment involves a device implanted into your body that stimulates your vagus nerve using electricity. This stimulation may affect your body’s production of mood-enhancing neurotransmitters, such as serotonin.

Your mental health provider may recommend these procedures on their own or in combination with therapy and/or medication. 

Make Changes to Your Habits and Lifestyle

Many forms of depression improve with healthy habits and lifestyle choices. 

Your mental health provider may recommend making changes to your lifestyle in combination with therapy, the use of medication and other treatments.

Common lifestyle changes that may help you cope if you’re experiencing depression include:

  • Getting plenty of cardiovascular and strength-building exercise 

  • Eating a balanced, healthy diet that’s rich in essential nutrients

  • Avoiding major life decisions while you're still feeling depressed

  • Spending time with your friends, family members and loved ones

  • Setting clear goals and working on making gradual, steady progress

  • Limiting your exposure to stressful people and/or situations

  • Closely following your depression treatment plan

Often, small changes to your habits and daily life can have a surprisingly large impact on your recovery from depression. Our guide to helping depression explains how you can change your lifestyle to improve your depression symptoms and make real, measurable progress. 

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Get Professional Help for Depression

Depression can be a serious, debilitating mental illness. When it doesn’t improve with therapy, medication or other conventional forms of treatment, it’s important to seek the help of a mental health professional to find out what you can do.

If you’re currently receiving care for depression from your primary care provider, ask them for a referral to a psychiatrist.

You can also connect with a licensed psychiatry provider from home using our online psychiatry service to receive a complete psychiatric evaluation, ongoing follow-up care and, if appropriate, prescription medication to help with your depression. 

Want to learn more about depression? Our guide to major depressive disorder goes into more detail about depression, from common symptoms to potential causes, effective treatments and more.

10 Sources

Hims & Hers has strict sourcing guidelines to ensure our content is accurate and current. We rely on peer-reviewed studies, academic research institutions, and medical associations. We strive to use primary sources and refrain from using tertiary references.

  1. Depression. (2018, February). Retrieved from https://www.nimh.nih.gov/health/topics/depression
  2. Al-Harbi, K.S. (2012). Treatment-resistant depression: therapeutic trends, challenges, and future directions. Patient Preference and Adherence. 6, 369–388. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3363299/
  3. Cuijpers, P., et al. (2014, February). Adding psychotherapy to antidepressant medication in depression and anxiety disorders: a meta-analysis. World Psychiatry. 13 (1), 56–67. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918025/
  4. What is Cognitive Behavioral Therapy? (2017, July). Retrieved from https://www.apa.org/ptsd-guideline/patients-and-families/cognitive-behavioral
  5. Interpersonal psychotherapy (IPT). (n.d.). Retrieved from https://dictionary.apa.org/interpersonal-psychotherapy
  6. Acceptance and Commitment Therapy. (n.d.). Retrieved from https://www.psychologytoday.com/us/therapy-types/acceptance-and-commitment-therapy
  7. Chapman, A.L. (2006, September). Dialectical Behavior Therapy. Psychiatry. 3 (9), 62–68. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963469/
  8. Jacobson, N.S., Martell, C.R. & Dimidjian, S. (2001). Behavioral activation treatment for depression: Returning to contextual roots. Clinical Psychology: Science and Practice. 8 (3), 255-270. Retrieved from https://psycnet.apa.org/record/2001-11076-001
  9. Sipe, W.E. & Eisendrath, S.J. (2012, February). Mindfulness-based cognitive therapy: theory and practice. The Canadian Journal of Psychiatry. 57 (2), 63-9. Retrieved from https://pubmed.ncbi.nlm.nih.gov/22340145/
  10. Brain Stimulation Therapies. (2016, June). Retrieved from https://www.nimh.nih.gov/health/topics/brain-stimulation-therapies/brain-stimulation-therapies

This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment. Learn more about our editorial standards here.