Symptoms of Treatment-Resistant Depression

Table of ContentsView AllTable of ContentsSigns and SymptomsComplications & ComorbiditiesTreatment-Resistant Depression and MisdiagnosisChronic Depression vs. Acute DepressionCan Treatment-Resistant Depression Be Treated?Is There Hope for Treatment-Resistant Depression?Depression Resources

Table of ContentsView All

View All

Table of Contents

Signs and Symptoms

Complications & Comorbidities

Treatment-Resistant Depression and Misdiagnosis

Chronic Depression vs. Acute Depression

Can Treatment-Resistant Depression Be Treated?

Is There Hope for Treatment-Resistant Depression?

Depression Resources

Close

Less than half of patients with depression can achieve full remission with the first treatment they receive,and approximately one-third of patients experiencetreatment-resistant depression(TRD).

Treatment-Resistant Depression

While multiple treatment approaches are effective, no single treatment is universally effective for all patients. So, if you’re beginning treatment for your depression, the process may involve some trial and error.

If you discover that various treatments are not working for you, you likely have treatment-resistant depression.

Treatment-Resistant Depression Symptoms

The primary symptoms of TRD include:

Experiencing these signs and symptoms with any treatment is enough for your doctor to determine that your depression is resistant to that particular treatment.

Little is known about why some patients respond to certain treatments but not others or why some don’t seem to respond to most available treatments. However, researchers have pinpointed some risk factors that make someone more likely to experience TRD.

Those risk factors include:

In addition, patients with certain forms of depression are more likely to be nonresponsive to one or more treatments.

What Else Can Increase Your Risk of TRD?Depression characteristics that increase your risk of TRD include:Psychotic symptoms like delusions or hallucinationsLonger lasting episodesMore frequent episodes

What Else Can Increase Your Risk of TRD?

Depression characteristics that increase your risk of TRD include:Psychotic symptoms like delusions or hallucinationsLonger lasting episodesMore frequent episodes

Depression characteristics that increase your risk of TRD include:

People Diagnosed With TRD May Have Been Misdiagnosed

If a patient with undetected asthma is not responding to allergy medication, diagnosing them with “treatment-resistant allergies” wouldn’t address the underlying source of their breathing problems. They did not receive the proper treatment.

Emerging research suggests that many TRD patients might not respond to treatment because they either have an undetected comorbid condition or a different condition altogether that was wrongly diagnosed as major depressive disorder. One study found that 34% of participants with TRD met the diagnostic criteria for ADHD, for example.

Another systematic review found that up to 50% of TRD patients met the criteria for bipolar spectrum disorder.ADHDand bipolar disorder are unlikely to respond toantidepressants, but these disorders do respond to other medications.

A TRD diagnosis is based on viewing depression as an acute condition, meaning the treatments you try in that trial-and-error phase are meant to be used for a short period and lead to full remission, sort of like taking a short course of antibiotics to fully eliminate an infection.

Understanding Depression as a Chronic Illness

“Difficult-to-Treat” DepressionOften preferring to call it “difficult-to-treat depression" (DTD), this chronic illness approach recognizes that it may be harder to treat, but it’s not impossible. It just requires a different understanding of what successful treatment outcomes look like and what a treatment plan should focus on.

“Difficult-to-Treat” Depression

Often preferring to call it “difficult-to-treat depression" (DTD), this chronic illness approach recognizes that it may be harder to treat, but it’s not impossible. It just requires a different understanding of what successful treatment outcomes look like and what a treatment plan should focus on.

Specifically, the DTD approach shifts the goal from full remission after acute treatment to optimal symptom control and overall improvement in quality of life. As a result, a long-term and holistic treatment approach is required. This type of treatment includes:

Instead of plain trial and error, the approach emphasizes frequent review to ensure no diagnosis is missed and no potentially beneficial treatment is overlooked.

Whether your depression is a chronic or an acute condition, the DTD approach can be helpful because it accounts for more of the complexities involved in treating and managing depression.

Yes, treatment-resistant depression can be treated. TRD means you aren’t responding to first-line depression therapies like antidepressants.

Still, various treatment approaches are available, including medication, psychotherapy, and even lifestyle changes.

The growing body of research on the link between TRD and undiagnosed conditions like ADHD or bipolar spectrum disorder should also be considered an encouraging sign. When a patient can get a correct diagnosis and switch to a more appropriate treatment plan for that condition, it often improves thedepressive symptomsin the process.

If you’ve run through multiple trials of antidepressants without success, that doesn’t mean you depression is untreatable. It just means you and your doctor might need to reevaluate your diagnosis and expand your scope of treatment options.

After multiple trials of different treatments with no success, it’s easy to feel hopeless and “incurable.” But there is still a path forward, even if you haven’t had any luck with antidepressants.

One study on the long-term outcomes of TRDfound that even with existing treatment options, most TRD patients can eventually achieve improved outcomes, whether full remission, partial remission or prolonged symptom-free periods between episodes.

The biggest predictor of a positive outcome for patients with TRD was having social support. So if you have friends or family that you feel safe reaching out to, do that. If you don’t, consider joining a support group to surround yourself with people who understand what you’re going through.

Here are some resources to help you find online and local depression support groups:

Ketamine Treatment

Outside of current treatment approaches, some emerging approaches have demonstrated especially hopeful signs of being able to treat TRD. Among those,ketaminemay be the most promising.

Several studies on TRD patients found that a ketamine infusion could significantly reduce depression, including suicidal ideation, in as little as three hours after treatment. The improvements lasted an average of 5 to 7 days.

The Best Online Therapy ProgramsWe’ve tried, tested and written unbiased reviews of the best online therapy programs including Talkspace, Betterhelp, and Regain.

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.Akil H, Gordon J, Hen R, et al.Treatment resistant depression: A multi-scale, systems biology approach. Neuroscience & Biobehavioral Reviews. 2018;84:272-288. Doi:10.1016/j.neubiorev.2017.08.019Ionescu DF, Rosenbaum JF, Alpert JE.Pharmacological approaches to the challenge of treatment-resistant depression. Dialogues in Clinical Neuroscience. 2015;17(2):111-126. Doi:10.31887/DCNS.2015.17.2/dionescuAl-harbi.Treatment-resistant depression: therapeutic trends, challenges, and future directions. PPA. Published online May 2012:369. Doi:10.2147/PPA.S29716Sternat T, Fotinos K, Fine A, Epstein I, Katzman MA.Low hedonic tone and attention-deficit hyperactivity disorder: risk factors for treatment resistance in depressed adults. Neuropsychiatr Dis Treat. 2018;14:2379-2387. Doi:10.2147/NDT.S170645Correa R, Akiskal H, Gilmer W, Nierenberg AA, Trivedi M, Zisook S.Is unrecognized bipolar disorder a frequent contributor to apparent treatment resistant depression?Journal of Affective Disorders. 2010;127(1-3):10-18. Doi: 0.1016/j.jad.2010.06.036Hamish McAllister-Williams R. Defining treatment-resistant depression, difficult-to-treat depression, and staging treatment intensity. Managing Treatment-Resistant Depression. Published online January 1, 2022:1-12. Doi:10.1016/B978-0-12-824067-0.00001-3Fekadu A, Rane LJ, Wooderson SC, Markopoulou K, Poon L, Cleare AJ.Prediction of longer-term outcome of treatment-resistant depression in tertiary care. BrJPsychiatry. 2012;201(5):369-375. Doi:10.1192/bjp.bp.111.102665Voineskos D, Daskalakis ZJ, Blumberger DM.Management of treatment-resistant depression: challenges and strategies. Neuropsychiatr Dis Treat. 2020;16:221-234. Doi:10.2147/NDT.S198774

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.Akil H, Gordon J, Hen R, et al.Treatment resistant depression: A multi-scale, systems biology approach. Neuroscience & Biobehavioral Reviews. 2018;84:272-288. Doi:10.1016/j.neubiorev.2017.08.019Ionescu DF, Rosenbaum JF, Alpert JE.Pharmacological approaches to the challenge of treatment-resistant depression. Dialogues in Clinical Neuroscience. 2015;17(2):111-126. Doi:10.31887/DCNS.2015.17.2/dionescuAl-harbi.Treatment-resistant depression: therapeutic trends, challenges, and future directions. PPA. Published online May 2012:369. Doi:10.2147/PPA.S29716Sternat T, Fotinos K, Fine A, Epstein I, Katzman MA.Low hedonic tone and attention-deficit hyperactivity disorder: risk factors for treatment resistance in depressed adults. Neuropsychiatr Dis Treat. 2018;14:2379-2387. Doi:10.2147/NDT.S170645Correa R, Akiskal H, Gilmer W, Nierenberg AA, Trivedi M, Zisook S.Is unrecognized bipolar disorder a frequent contributor to apparent treatment resistant depression?Journal of Affective Disorders. 2010;127(1-3):10-18. Doi: 0.1016/j.jad.2010.06.036Hamish McAllister-Williams R. Defining treatment-resistant depression, difficult-to-treat depression, and staging treatment intensity. Managing Treatment-Resistant Depression. Published online January 1, 2022:1-12. Doi:10.1016/B978-0-12-824067-0.00001-3Fekadu A, Rane LJ, Wooderson SC, Markopoulou K, Poon L, Cleare AJ.Prediction of longer-term outcome of treatment-resistant depression in tertiary care. BrJPsychiatry. 2012;201(5):369-375. Doi:10.1192/bjp.bp.111.102665Voineskos D, Daskalakis ZJ, Blumberger DM.Management of treatment-resistant depression: challenges and strategies. Neuropsychiatr Dis Treat. 2020;16:221-234. Doi:10.2147/NDT.S198774

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.

Akil H, Gordon J, Hen R, et al.Treatment resistant depression: A multi-scale, systems biology approach. Neuroscience & Biobehavioral Reviews. 2018;84:272-288. Doi:10.1016/j.neubiorev.2017.08.019Ionescu DF, Rosenbaum JF, Alpert JE.Pharmacological approaches to the challenge of treatment-resistant depression. Dialogues in Clinical Neuroscience. 2015;17(2):111-126. Doi:10.31887/DCNS.2015.17.2/dionescuAl-harbi.Treatment-resistant depression: therapeutic trends, challenges, and future directions. PPA. Published online May 2012:369. Doi:10.2147/PPA.S29716Sternat T, Fotinos K, Fine A, Epstein I, Katzman MA.Low hedonic tone and attention-deficit hyperactivity disorder: risk factors for treatment resistance in depressed adults. Neuropsychiatr Dis Treat. 2018;14:2379-2387. Doi:10.2147/NDT.S170645Correa R, Akiskal H, Gilmer W, Nierenberg AA, Trivedi M, Zisook S.Is unrecognized bipolar disorder a frequent contributor to apparent treatment resistant depression?Journal of Affective Disorders. 2010;127(1-3):10-18. Doi: 0.1016/j.jad.2010.06.036Hamish McAllister-Williams R. Defining treatment-resistant depression, difficult-to-treat depression, and staging treatment intensity. Managing Treatment-Resistant Depression. Published online January 1, 2022:1-12. Doi:10.1016/B978-0-12-824067-0.00001-3Fekadu A, Rane LJ, Wooderson SC, Markopoulou K, Poon L, Cleare AJ.Prediction of longer-term outcome of treatment-resistant depression in tertiary care. BrJPsychiatry. 2012;201(5):369-375. Doi:10.1192/bjp.bp.111.102665Voineskos D, Daskalakis ZJ, Blumberger DM.Management of treatment-resistant depression: challenges and strategies. Neuropsychiatr Dis Treat. 2020;16:221-234. Doi:10.2147/NDT.S198774

Akil H, Gordon J, Hen R, et al.Treatment resistant depression: A multi-scale, systems biology approach. Neuroscience & Biobehavioral Reviews. 2018;84:272-288. Doi:10.1016/j.neubiorev.2017.08.019

Ionescu DF, Rosenbaum JF, Alpert JE.Pharmacological approaches to the challenge of treatment-resistant depression. Dialogues in Clinical Neuroscience. 2015;17(2):111-126. Doi:10.31887/DCNS.2015.17.2/dionescu

Al-harbi.Treatment-resistant depression: therapeutic trends, challenges, and future directions. PPA. Published online May 2012:369. Doi:10.2147/PPA.S29716

Sternat T, Fotinos K, Fine A, Epstein I, Katzman MA.Low hedonic tone and attention-deficit hyperactivity disorder: risk factors for treatment resistance in depressed adults. Neuropsychiatr Dis Treat. 2018;14:2379-2387. Doi:10.2147/NDT.S170645

Correa R, Akiskal H, Gilmer W, Nierenberg AA, Trivedi M, Zisook S.Is unrecognized bipolar disorder a frequent contributor to apparent treatment resistant depression?Journal of Affective Disorders. 2010;127(1-3):10-18. Doi: 0.1016/j.jad.2010.06.036

Hamish McAllister-Williams R. Defining treatment-resistant depression, difficult-to-treat depression, and staging treatment intensity. Managing Treatment-Resistant Depression. Published online January 1, 2022:1-12. Doi:10.1016/B978-0-12-824067-0.00001-3

Fekadu A, Rane LJ, Wooderson SC, Markopoulou K, Poon L, Cleare AJ.Prediction of longer-term outcome of treatment-resistant depression in tertiary care. BrJPsychiatry. 2012;201(5):369-375. Doi:10.1192/bjp.bp.111.102665

Voineskos D, Daskalakis ZJ, Blumberger DM.Management of treatment-resistant depression: challenges and strategies. Neuropsychiatr Dis Treat. 2020;16:221-234. Doi:10.2147/NDT.S198774

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