An Overview of Treatment-Resistant Depression

Table of ContentsView AllTable of ContentsPrevalenceSymptomsCausesDiagnosisTreatmentCoping

Table of ContentsView All

View All

Table of Contents

Prevalence

Symptoms

Causes

Diagnosis

Treatment

Coping

Close

Depression is usually managed with medication, therapy, or a combination of the two, and usually,symptomsresolve with treatment. But sometimes, symptoms don’t get better with typical treatment.

Although definitions may vary, when two or more treatment attempts of adequate dose and duration fail to provide expected relief, the disorder may be considered “treatment-resistant depression.”

Treatment-resistant depression can be complex.Depression symptoms, such as sleep issues and appetite problems, may continue despite patient compliance with treatment. At other times, the symptoms resolve briefly but come back.

It’s important to remember that even if depression does not respond to the first couple of treatments, that doesn’t mean it cannot be treated. However, it may require a different approach to treatment. It would be best if you worked with your doctor to monitor your symptoms and response totreatmentso that you can find an option that works for you.

Studies have found that 30% to 40% of people only experience a partial remission of depressive symptoms after taking antidepressants.Approximately 10% to 15% of people don’t respond to antidepressant treatments at all.

The consequences for people with treatment-resistant depression can be significant. It’s associated with poor social functioning, medical comorbidity, and increased mortality.

Untreated depression is also a common cause of disability, so it’s important to continue trying to find strategies that can bring relief.

People with untreated depression have a lifetimesuicide riskof 2% to 15%.

Treatment-resistant depression can manifest as:

Because standard treatments do not work well or at all, people may begin to experience profoundhopelessness. Symptoms can drag on for months without feeling any relief or improvement in mood.

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Doctors and researchers are not entirely sure what causes treatment-resistant depression. Some theories include:

If you have been treated for depression but your symptoms have not improved, you should talk to your doctor. Treatment-resistant depression is not anofficialdiagnosis included in theDiagnostic and Statistical Manual of Mental Disorders(DSM-5-TR), nor is it consistently defined. Some experts suggest that it is defined as having had two different antidepressant trials without relief, while others suggest that it can take as many as four different treatments before depression should be identified as resistant.

In any case, you should always talk to your doctor about your symptoms and concerns. If you have not experienced any relief, only minimal relief, or a complete return of symptoms, you may need a differenttype of antidepressantor alternative approaches to your treatment.

Your doctor may:

If your doctor believes that you have treatment-resistant depression, they may recommend a different dosage, medication, combination of medications, or a different treatment approach altogether. Your doctor may also refer you to a neuropsychiatric consultant for additional treatment advice and options.

While estimates vary, it is believed that anywhere 30% to 50% of patients with depression may not respond to a particular antidepressant medication. Before a physician or psychiatrist will consider a medication a treatment failure, they will consider the following questions:

How Treatment-Resistant Depression is Treated

Medications

If a psychiatrist determines that your current medication is a failure, there are some other treatment options that affectbrain chemistryin a different way. Those options include:

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Talk Therapy

If you aren’t already attending psychotherapy, a referral may be made to a mental health professional who offers it.

While there are many different types of psychotherapy that have been found to be beneficial in depression,cognitive behavioral therapy(CBT) has data that found it effective for treatment-resistant depression.

Patients attending CBT may learn various skills to manage their symptoms and improve their functioning.

CBT goals often involve reframing negative thoughts, problem-solving, increasing social interaction, and increasing activity levels. It may also help reduce sleep problems.

Other therapy types that may also be helpful includeinterpersonal therapy,dialectical behavioral therapy, andpsychodynamic therapyin both individual and group settings.

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Other Treatment Options

When medication and therapy aren’t reducing depression, your doctor may decide to turn to other treatment options. Here are some additional procedures that may be effective for treatment-resistant depression:

Transcranial Magnetic Stimulation vs. Electroconvulsive Therapy

Dealing with treatment-resistant depression can be difficult for a number of reasons. Not only are you coping with persistent symptoms of depression, but you are also struggling with the difficulty in treating your condition.

Some of the things you can do that can help:

If you are having suicidal thoughts, contact theNational Suicide Prevention Lifelineat988for support and assistance from a trained counselor. If you or a loved one are in immediate danger, call 911.For more mental health resources, see ourNational Helpline Database.

If you are having suicidal thoughts, contact theNational Suicide Prevention Lifelineat988for support and assistance from a trained counselor. If you or a loved one are in immediate danger, call 911.

For more mental health resources, see ourNational Helpline Database.

Final Thoughts

If you or a loved one is experiencing depression and medication isn’t working, don’t give up. Talk to your physician or psychiatrist about other treatment options. It may take several attempts to find something that works well for you, but it’s important to keep trying so that you can experience relief from your symptoms.

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8 SourcesVerywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Tundo A, de Filippis R, Proietti L.Pharmacologic approaches to treatment resistant depression: Evidences and personal experience.World J Psychiatry. 2015;5(3):330-341. doi:10.5498/wjp.v5.i3.330Center for Suicide Prevention.Depression and suicide prevention.Fabbri C, Corponi F, Souery D, et al.The genetics of treatment-resistant depression: A critical review and future perspectives.Int J Neuropsychopharmacol. 2019;22(2):93-104. doi:10.1093/ijnp/pyy024Pan LA, Martin P, Zimmer T, et al.Neurometabolic disorders: Potentially treatable abnormalities in patients with treatment-refractory depression and suicidal behavior.Am J Psychiatry. 2017;174(1):42-50. doi:10.1176/appi.ajp.2016.15111500Gerhard T, Stroup TS, Correll CU, et al.Mortality risk of antipsychotic augmentation for adult depression.PLoS One. 2020;15(9):e0239206. doi:10.1371/journal.pone.0239206Li JM, Zhang Y, Su WJ, et al.Cognitive-behavioral therapy for treatment-resistant depression: A systematic review and meta-analysis.Psychiatry Res. 2018;268:243-250. doi:10.1016/j.psychres.2018.07.020Nakagawa A, Mitsuda D, Sado M, et al.Effectiveness of supplementary cognitive-behavioral therapy for pharmacotherapy-resistant depression: A randomized controlled trial.J Clin Psychiatry. 2017;78(8):2450.Rizvi S, Khan AM.Use of transcranial magnetic stimulation for depression.Cureus.2019;11(5):e4736. doi::10.7759%2Fcureus.4736Additional ReadingFekadu A, Wooderson SC, Markopoulou K, Cleare AJ.The maudsley staging method for treatment-resistant depression: Prediction of longer-term outcome and persistence of symptoms.J Clin Psychiatry. 2009;70(7):952-7. doi:10.4088/JCP.08m04728Ge R, Downar J, Blumberger DM, Daskalakis ZJ, Lam RW, Vila-Rodriguez F.Structural network integrity of the central executive network is associated with the therapeutic effect of rTMS in treatment resistant depression.Prog Neuropsychopharmacol Biol Psychiatry. 2019;92:217-225. doi:10.1016/j.pnpbp.2019.01.012Lex H, Ginsburg Y, Sitzmann AF, Grayhack C, Maixner DF, Mickey BJ.Quality of life across domains among individuals with treatment-resistant depression.J Affect Disord. 2019;243:401-407. doi:10.1016/j.jad.2018.09.062

8 Sources

Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Tundo A, de Filippis R, Proietti L.Pharmacologic approaches to treatment resistant depression: Evidences and personal experience.World J Psychiatry. 2015;5(3):330-341. doi:10.5498/wjp.v5.i3.330Center for Suicide Prevention.Depression and suicide prevention.Fabbri C, Corponi F, Souery D, et al.The genetics of treatment-resistant depression: A critical review and future perspectives.Int J Neuropsychopharmacol. 2019;22(2):93-104. doi:10.1093/ijnp/pyy024Pan LA, Martin P, Zimmer T, et al.Neurometabolic disorders: Potentially treatable abnormalities in patients with treatment-refractory depression and suicidal behavior.Am J Psychiatry. 2017;174(1):42-50. doi:10.1176/appi.ajp.2016.15111500Gerhard T, Stroup TS, Correll CU, et al.Mortality risk of antipsychotic augmentation for adult depression.PLoS One. 2020;15(9):e0239206. doi:10.1371/journal.pone.0239206Li JM, Zhang Y, Su WJ, et al.Cognitive-behavioral therapy for treatment-resistant depression: A systematic review and meta-analysis.Psychiatry Res. 2018;268:243-250. doi:10.1016/j.psychres.2018.07.020Nakagawa A, Mitsuda D, Sado M, et al.Effectiveness of supplementary cognitive-behavioral therapy for pharmacotherapy-resistant depression: A randomized controlled trial.J Clin Psychiatry. 2017;78(8):2450.Rizvi S, Khan AM.Use of transcranial magnetic stimulation for depression.Cureus.2019;11(5):e4736. doi::10.7759%2Fcureus.4736Additional ReadingFekadu A, Wooderson SC, Markopoulou K, Cleare AJ.The maudsley staging method for treatment-resistant depression: Prediction of longer-term outcome and persistence of symptoms.J Clin Psychiatry. 2009;70(7):952-7. doi:10.4088/JCP.08m04728Ge R, Downar J, Blumberger DM, Daskalakis ZJ, Lam RW, Vila-Rodriguez F.Structural network integrity of the central executive network is associated with the therapeutic effect of rTMS in treatment resistant depression.Prog Neuropsychopharmacol Biol Psychiatry. 2019;92:217-225. doi:10.1016/j.pnpbp.2019.01.012Lex H, Ginsburg Y, Sitzmann AF, Grayhack C, Maixner DF, Mickey BJ.Quality of life across domains among individuals with treatment-resistant depression.J Affect Disord. 2019;243:401-407. doi:10.1016/j.jad.2018.09.062

Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

Tundo A, de Filippis R, Proietti L.Pharmacologic approaches to treatment resistant depression: Evidences and personal experience.World J Psychiatry. 2015;5(3):330-341. doi:10.5498/wjp.v5.i3.330Center for Suicide Prevention.Depression and suicide prevention.Fabbri C, Corponi F, Souery D, et al.The genetics of treatment-resistant depression: A critical review and future perspectives.Int J Neuropsychopharmacol. 2019;22(2):93-104. doi:10.1093/ijnp/pyy024Pan LA, Martin P, Zimmer T, et al.Neurometabolic disorders: Potentially treatable abnormalities in patients with treatment-refractory depression and suicidal behavior.Am J Psychiatry. 2017;174(1):42-50. doi:10.1176/appi.ajp.2016.15111500Gerhard T, Stroup TS, Correll CU, et al.Mortality risk of antipsychotic augmentation for adult depression.PLoS One. 2020;15(9):e0239206. doi:10.1371/journal.pone.0239206Li JM, Zhang Y, Su WJ, et al.Cognitive-behavioral therapy for treatment-resistant depression: A systematic review and meta-analysis.Psychiatry Res. 2018;268:243-250. doi:10.1016/j.psychres.2018.07.020Nakagawa A, Mitsuda D, Sado M, et al.Effectiveness of supplementary cognitive-behavioral therapy for pharmacotherapy-resistant depression: A randomized controlled trial.J Clin Psychiatry. 2017;78(8):2450.Rizvi S, Khan AM.Use of transcranial magnetic stimulation for depression.Cureus.2019;11(5):e4736. doi::10.7759%2Fcureus.4736

Tundo A, de Filippis R, Proietti L.Pharmacologic approaches to treatment resistant depression: Evidences and personal experience.World J Psychiatry. 2015;5(3):330-341. doi:10.5498/wjp.v5.i3.330

Center for Suicide Prevention.Depression and suicide prevention.

Fabbri C, Corponi F, Souery D, et al.The genetics of treatment-resistant depression: A critical review and future perspectives.Int J Neuropsychopharmacol. 2019;22(2):93-104. doi:10.1093/ijnp/pyy024

Pan LA, Martin P, Zimmer T, et al.Neurometabolic disorders: Potentially treatable abnormalities in patients with treatment-refractory depression and suicidal behavior.Am J Psychiatry. 2017;174(1):42-50. doi:10.1176/appi.ajp.2016.15111500

Gerhard T, Stroup TS, Correll CU, et al.Mortality risk of antipsychotic augmentation for adult depression.PLoS One. 2020;15(9):e0239206. doi:10.1371/journal.pone.0239206

Li JM, Zhang Y, Su WJ, et al.Cognitive-behavioral therapy for treatment-resistant depression: A systematic review and meta-analysis.Psychiatry Res. 2018;268:243-250. doi:10.1016/j.psychres.2018.07.020

Nakagawa A, Mitsuda D, Sado M, et al.Effectiveness of supplementary cognitive-behavioral therapy for pharmacotherapy-resistant depression: A randomized controlled trial.J Clin Psychiatry. 2017;78(8):2450.

Rizvi S, Khan AM.Use of transcranial magnetic stimulation for depression.Cureus.2019;11(5):e4736. doi::10.7759%2Fcureus.4736

Fekadu A, Wooderson SC, Markopoulou K, Cleare AJ.The maudsley staging method for treatment-resistant depression: Prediction of longer-term outcome and persistence of symptoms.J Clin Psychiatry. 2009;70(7):952-7. doi:10.4088/JCP.08m04728Ge R, Downar J, Blumberger DM, Daskalakis ZJ, Lam RW, Vila-Rodriguez F.Structural network integrity of the central executive network is associated with the therapeutic effect of rTMS in treatment resistant depression.Prog Neuropsychopharmacol Biol Psychiatry. 2019;92:217-225. doi:10.1016/j.pnpbp.2019.01.012Lex H, Ginsburg Y, Sitzmann AF, Grayhack C, Maixner DF, Mickey BJ.Quality of life across domains among individuals with treatment-resistant depression.J Affect Disord. 2019;243:401-407. doi:10.1016/j.jad.2018.09.062

Fekadu A, Wooderson SC, Markopoulou K, Cleare AJ.The maudsley staging method for treatment-resistant depression: Prediction of longer-term outcome and persistence of symptoms.J Clin Psychiatry. 2009;70(7):952-7. doi:10.4088/JCP.08m04728

Ge R, Downar J, Blumberger DM, Daskalakis ZJ, Lam RW, Vila-Rodriguez F.Structural network integrity of the central executive network is associated with the therapeutic effect of rTMS in treatment resistant depression.Prog Neuropsychopharmacol Biol Psychiatry. 2019;92:217-225. doi:10.1016/j.pnpbp.2019.01.012

Lex H, Ginsburg Y, Sitzmann AF, Grayhack C, Maixner DF, Mickey BJ.Quality of life across domains among individuals with treatment-resistant depression.J Affect Disord. 2019;243:401-407. doi:10.1016/j.jad.2018.09.062

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