How Treatment-Resistant Depression is Treated

Table of ContentsView AllTable of ContentsPsychotherapyMedicationSurgery and Neuro-Therapeutic ProceduresCAM & OTC OptionsDiet and ExerciseOther OptionsMaximize Your Treatment

Table of ContentsView All

View All

Table of Contents

Psychotherapy

Medication

Surgery and Neuro-Therapeutic Procedures

CAM & OTC Options

Diet and Exercise

Other Options

Maximize Your Treatment

Treatment-resistant depression (TRD) is defined as depression that does not adequately respond after trying at least two medications. TRD is not an official DSM diagnosis, but it is used to identify those who may be candidates for different types of treatments.

The major areas of treatment for TRD are medications (including everything from SSRIs to antipsychotics), psychotherapy, ketamine and more invasive procedures, such as electroconvulsive therapy. People with treatment-resistant depression are more likely to be hospitalized and/or attempt suicide,so it is key to find adequate ways of treatment that work—and quickly.

Read on to learn more about some treatments that may work for depression that has previously been treatment-resistant.

Symptoms of Treatment-Resistant Depression

In studies of psychotherapy in addition to usual care, the following psychotherapies were successful in achieving a reduction in depression symptoms/scores, both self reported and via depression scales such asPHQorHAMS-(D).

Additionally, as many people withtreatment-resistant depressionmay tend to isolate, having steady contact with a therapist can be helpful. Moreover, many studies have confirmed that psychotherapy and medication typically work synergistically, magnifying the effects of each other.

Below are some of the psychotherapies that have been proven helpful for TRD:

Cognitive Therapies

Most people who are diagnosed with major depressive disorder (which is what you are generally diagnosed with and treated for before it progresses to TRD) are started on SSRIs or SNRIs. However, anywhere up to a third of people do not respond to SSRIs/SNRIs.Because this is so common, psychiatrists often use the following treatment algorithm to determine next steps:

The biggest drawback to any of these more traditional medications is how long it takes them to work. Many of them may take up to six weeks to work fully—which can feel like an eternity when you’re struggling. Additionally, they may come with sexual side effects or side effects like weight gain.

Much research is being done right now indepression treatmentand several of the below treatments have either been approved or appear to be on the precipice of it:

Complementary Alternative Medicine (CAM) & Over-the-Counter (OTC)

While no real “over the counter” remedies exist for depression the way they do for, say, allergies, there are some supplements and other over-the-counter products that may help with depression as well as other types of complementary and alternative medicine (CAM) that might have potential benefit.

If you are dealing with treatment-resistant depression, your mind likely isn’t on eating healthfully or exercising, but what we put into our bodies and how we move them can have a real effect on our mental health.

Diet

When you’re dealing with treatment-resistant depression, it’s likely your eating habits are affected. You’re either eating too much, not enough, or eating lots of comfort food, which may raise inflammation levels, which are thought to contribute totreatment-resistant depression.

But you don’t have to overhaul your whole diet all at once. Small changes, such as reducing processed food in your diet and remembering to eat breakfast may go a long way.

Exercise

Yoga:If you had a dollar for every time someone has asked you if you’ve triedyoga, you’d probably be able to pay for your treatment on just that. But it’s for good reason—while it won’tcuredepression, it may reduce the symptoms and severity of it.

Walking:If, when you’re not depressed, you’re typically a person who goes hard on their exercise, you may scoff at the idea of walking for depression. However, walking and other moderate-intensity exercise, when done regularly, may even lead to improvement of depression symptoms.

Things You Can Try on Your Own

While treatment-resistant depression is incredibly serious and does require working with a professional, therearesome other types of treatments you can do at home/on your own.

Over-the-Counter Antidepressants

How to Make Your Treatment Most Effective

Medication Adherence

If you are not taking your medication daily or regularly as prescribed, it can be hard for it to be effective. Depression, however, can also make remembering to take it in the first place difficult. Some strategies that may help include setting a timer on your phone, using a pill case, or keeping your medications out in a place where you can’t miss them.

Avoid Alcohol and Other Drugs

Alcohol is a depressant, so it may make your depression worseandnegate any help that your antidepressantsaregiving you, for a double whammy. Other drugs, particularly addictive ones, may cause further mental health issues.

Minimize Stress

We know, we know, easier said than done! However, stress only aggravates feelings and symptoms of depression.While there are plenty of stressful situations that are beyond our control, what we can control is how we deal with those situations as well as not inflicting any unnecessary stress on ourselves.Self-compassioncan go a long way in helping deal with stress.

Consider Cost

Unfortunately, in the United States, mental health treatment can be incredibly costly and out of the reach of many. However, going into debt for your depression treatment will only create more stress, so look into things like reduced fee treatments.

20 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.Souery D, Oswald P, Massat I, et al.Clinical factors associated with treatment resistance in major depressive disorder: results from a European multicenter study. J Clin Psychiatry. 2007;68(7):1062-1070. DOI: 10.4088/jcp.v68n0713Wiles N, Williams CJ, Kessler D, Lewis G.Psychological therapies for treatment-resistant depression in adults. Cochrane Common Mental Disorders Group, ed. Cochrane Database of Systematic Reviews. DOI: 10.1002/14651858.CD010558.pub2Markowitz JC, Wright JH, Peeters F, Thase ME, Kocsis JH, Sudak DM.The neglected role of psychotherapy for treatment-resistant depression. AJP. 2022;179(2):90-93. DOI: 10.1176/appi.ajp.2021.21050535Voineskos D, Daskalakis ZJ, Blumberger DM.Management of treatment-resistant depression: challenges and strategies. Neuropsychiatr Dis Treat. 2020;16:221-234. DOI: 10.2147/NDT.S198774Abbass AA.Intensive Short-Term Dynamic Psychotherapy of treatment-resistant depression: a pilot study. Depress Anxiety. 2006;23(7):449-452. DOI: 10.1002/da.20203Al-Harbi KS.Treatment-resistant depression: therapeutic trends, challenges, and future directions. Patient Prefer Adherence. 2012;6:369-388. DOI: 10.2147/PPA.S29716Goodwin GM, Aaronson ST, Alvarez O, et al.Single-dose psilocybin for a treatment-resistant episode of major depression.N Engl J Med. 2022;387(18):1637-1648. DOI: 10.1056/NEJMoa2206443Cole EJ, Stimpson KH, Bentzley BS, et al.Stanford accelerated intelligent neuromodulation therapy for treatment-resistant depression.AJP. 2020;177(8):716-726. DOI: 10.1176/appi.ajp.2021.20101429Pycroft L, Stein J, Aziz T.Deep brain stimulation: An overview of history, methods, and future developments. Brain and Neuroscience Advances. 2018;2:239821281881601. DOI: 10.1177/2398212818816017Brus O, Cao Y, Gustafsson E, et al.Self-assessed remission rates after electroconvulsive therapy of depressive disorders. Eur psychiatr. 2017;45:154-160. DOI: 10.1016/j.eurpsy.2017.06.015Deane KHO, Jimoh OF, Biswas P, et al.Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials. The British Journal of Psychiatry. 2021;218(3):135-142. DOI: 10.1192/bjp.2019.234Iovieno N, Dalton ED, Fava M, Mischoulon D.Second-tier natural antidepressants: Review and critique. Journal of Affective Disorders. 2011;130(3):343-357. DOI: 10.1016/j.jad.2010.06.010Dome P, Tombor L, Lazary J, Gonda X, Rihmer Z.Natural health products, dietary minerals and over-the-counter medications as add-on therapies to antidepressants in the treatment of major depressive disorder: a review. Brain Research Bulletin. 2019;146:51-78. DOI: 10.1016/j.brainresbull.2018.12.015Smith CA, Armour M, Lee MS, Wang LQ, Hay PJ.Acupuncture for depression. Cochrane Database of Systematic Reviews. 2018;(3). DOI: 10.1002/14651858.CD004046.pub4.Brinsley J, Schuch F, Lederman O, et al.Effects of yoga on depressive symptoms in people with mental disorders: a systematic review and meta-analysis. Br J Sports Med. 2021;55(17):992-1000. DOI: 10.1136/bjsports-2019-101242Mota-Pereira J, Silverio J, Carvalho S, Ribeiro JC, Fonte D, Ramos J.Moderate exercise improves depression parameters in treatment-resistant patients with major depressive disorder. J Psychiatr Res. 2011;45(8):1005-1011. DOI: 10.1016/j.jpsychires.2011.02.005Bookworms versus nerds: Exposure to fiction versus non-fiction, divergent associations with social ability, and the simulation of fictional social worlds.Journal of Research in Personality. 2006;40(5):694-712. DOI: 10.1016/j.jrp.2005.08.002Gualano MR, Bert F, Martorana M, et al.The long-term effects of bibliotherapy in depression treatment: Systematic review of randomized clinical trials. Clinical Psychology Review. 2017;58:49-58. DOI: 10.1016/j.cpr.2017.09.006Krpan KM, Kross E, Berman MG, Deldin PJ, Askren MK, Jonides J.An everyday activity as a treatment for depression: The benefits of expressive writing for people diagnosed with major depressive disorder. J Affect Disord. 2013;150(3):1148-1151. DOI: 10.1016/j.jad.2013.05.065Yang L, Zhao Y, Wang Y, et al.The effects of psychological stress on depression. Curr Neuropharmacol. 2015;13(4):494-504. DOI: 10.2174/1570159X1304150831150507

20 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.Souery D, Oswald P, Massat I, et al.Clinical factors associated with treatment resistance in major depressive disorder: results from a European multicenter study. J Clin Psychiatry. 2007;68(7):1062-1070. DOI: 10.4088/jcp.v68n0713Wiles N, Williams CJ, Kessler D, Lewis G.Psychological therapies for treatment-resistant depression in adults. Cochrane Common Mental Disorders Group, ed. Cochrane Database of Systematic Reviews. DOI: 10.1002/14651858.CD010558.pub2Markowitz JC, Wright JH, Peeters F, Thase ME, Kocsis JH, Sudak DM.The neglected role of psychotherapy for treatment-resistant depression. AJP. 2022;179(2):90-93. DOI: 10.1176/appi.ajp.2021.21050535Voineskos D, Daskalakis ZJ, Blumberger DM.Management of treatment-resistant depression: challenges and strategies. Neuropsychiatr Dis Treat. 2020;16:221-234. DOI: 10.2147/NDT.S198774Abbass AA.Intensive Short-Term Dynamic Psychotherapy of treatment-resistant depression: a pilot study. Depress Anxiety. 2006;23(7):449-452. DOI: 10.1002/da.20203Al-Harbi KS.Treatment-resistant depression: therapeutic trends, challenges, and future directions. Patient Prefer Adherence. 2012;6:369-388. DOI: 10.2147/PPA.S29716Goodwin GM, Aaronson ST, Alvarez O, et al.Single-dose psilocybin for a treatment-resistant episode of major depression.N Engl J Med. 2022;387(18):1637-1648. DOI: 10.1056/NEJMoa2206443Cole EJ, Stimpson KH, Bentzley BS, et al.Stanford accelerated intelligent neuromodulation therapy for treatment-resistant depression.AJP. 2020;177(8):716-726. DOI: 10.1176/appi.ajp.2021.20101429Pycroft L, Stein J, Aziz T.Deep brain stimulation: An overview of history, methods, and future developments. Brain and Neuroscience Advances. 2018;2:239821281881601. DOI: 10.1177/2398212818816017Brus O, Cao Y, Gustafsson E, et al.Self-assessed remission rates after electroconvulsive therapy of depressive disorders. Eur psychiatr. 2017;45:154-160. DOI: 10.1016/j.eurpsy.2017.06.015Deane KHO, Jimoh OF, Biswas P, et al.Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials. The British Journal of Psychiatry. 2021;218(3):135-142. DOI: 10.1192/bjp.2019.234Iovieno N, Dalton ED, Fava M, Mischoulon D.Second-tier natural antidepressants: Review and critique. Journal of Affective Disorders. 2011;130(3):343-357. DOI: 10.1016/j.jad.2010.06.010Dome P, Tombor L, Lazary J, Gonda X, Rihmer Z.Natural health products, dietary minerals and over-the-counter medications as add-on therapies to antidepressants in the treatment of major depressive disorder: a review. Brain Research Bulletin. 2019;146:51-78. DOI: 10.1016/j.brainresbull.2018.12.015Smith CA, Armour M, Lee MS, Wang LQ, Hay PJ.Acupuncture for depression. Cochrane Database of Systematic Reviews. 2018;(3). DOI: 10.1002/14651858.CD004046.pub4.Brinsley J, Schuch F, Lederman O, et al.Effects of yoga on depressive symptoms in people with mental disorders: a systematic review and meta-analysis. Br J Sports Med. 2021;55(17):992-1000. DOI: 10.1136/bjsports-2019-101242Mota-Pereira J, Silverio J, Carvalho S, Ribeiro JC, Fonte D, Ramos J.Moderate exercise improves depression parameters in treatment-resistant patients with major depressive disorder. J Psychiatr Res. 2011;45(8):1005-1011. DOI: 10.1016/j.jpsychires.2011.02.005Bookworms versus nerds: Exposure to fiction versus non-fiction, divergent associations with social ability, and the simulation of fictional social worlds.Journal of Research in Personality. 2006;40(5):694-712. DOI: 10.1016/j.jrp.2005.08.002Gualano MR, Bert F, Martorana M, et al.The long-term effects of bibliotherapy in depression treatment: Systematic review of randomized clinical trials. Clinical Psychology Review. 2017;58:49-58. DOI: 10.1016/j.cpr.2017.09.006Krpan KM, Kross E, Berman MG, Deldin PJ, Askren MK, Jonides J.An everyday activity as a treatment for depression: The benefits of expressive writing for people diagnosed with major depressive disorder. J Affect Disord. 2013;150(3):1148-1151. DOI: 10.1016/j.jad.2013.05.065Yang L, Zhao Y, Wang Y, et al.The effects of psychological stress on depression. Curr Neuropharmacol. 2015;13(4):494-504. DOI: 10.2174/1570159X1304150831150507

Souery D, Oswald P, Massat I, et al.Clinical factors associated with treatment resistance in major depressive disorder: results from a European multicenter study. J Clin Psychiatry. 2007;68(7):1062-1070. DOI: 10.4088/jcp.v68n0713Wiles N, Williams CJ, Kessler D, Lewis G.Psychological therapies for treatment-resistant depression in adults. Cochrane Common Mental Disorders Group, ed. Cochrane Database of Systematic Reviews. DOI: 10.1002/14651858.CD010558.pub2Markowitz JC, Wright JH, Peeters F, Thase ME, Kocsis JH, Sudak DM.The neglected role of psychotherapy for treatment-resistant depression. AJP. 2022;179(2):90-93. DOI: 10.1176/appi.ajp.2021.21050535Voineskos D, Daskalakis ZJ, Blumberger DM.Management of treatment-resistant depression: challenges and strategies. Neuropsychiatr Dis Treat. 2020;16:221-234. DOI: 10.2147/NDT.S198774Abbass AA.Intensive Short-Term Dynamic Psychotherapy of treatment-resistant depression: a pilot study. Depress Anxiety. 2006;23(7):449-452. DOI: 10.1002/da.20203Al-Harbi KS.Treatment-resistant depression: therapeutic trends, challenges, and future directions. Patient Prefer Adherence. 2012;6:369-388. DOI: 10.2147/PPA.S29716Goodwin GM, Aaronson ST, Alvarez O, et al.Single-dose psilocybin for a treatment-resistant episode of major depression.N Engl J Med. 2022;387(18):1637-1648. DOI: 10.1056/NEJMoa2206443Cole EJ, Stimpson KH, Bentzley BS, et al.Stanford accelerated intelligent neuromodulation therapy for treatment-resistant depression.AJP. 2020;177(8):716-726. DOI: 10.1176/appi.ajp.2021.20101429Pycroft L, Stein J, Aziz T.Deep brain stimulation: An overview of history, methods, and future developments. Brain and Neuroscience Advances. 2018;2:239821281881601. DOI: 10.1177/2398212818816017Brus O, Cao Y, Gustafsson E, et al.Self-assessed remission rates after electroconvulsive therapy of depressive disorders. Eur psychiatr. 2017;45:154-160. DOI: 10.1016/j.eurpsy.2017.06.015Deane KHO, Jimoh OF, Biswas P, et al.Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials. The British Journal of Psychiatry. 2021;218(3):135-142. DOI: 10.1192/bjp.2019.234Iovieno N, Dalton ED, Fava M, Mischoulon D.Second-tier natural antidepressants: Review and critique. Journal of Affective Disorders. 2011;130(3):343-357. DOI: 10.1016/j.jad.2010.06.010Dome P, Tombor L, Lazary J, Gonda X, Rihmer Z.Natural health products, dietary minerals and over-the-counter medications as add-on therapies to antidepressants in the treatment of major depressive disorder: a review. Brain Research Bulletin. 2019;146:51-78. DOI: 10.1016/j.brainresbull.2018.12.015Smith CA, Armour M, Lee MS, Wang LQ, Hay PJ.Acupuncture for depression. Cochrane Database of Systematic Reviews. 2018;(3). DOI: 10.1002/14651858.CD004046.pub4.Brinsley J, Schuch F, Lederman O, et al.Effects of yoga on depressive symptoms in people with mental disorders: a systematic review and meta-analysis. Br J Sports Med. 2021;55(17):992-1000. DOI: 10.1136/bjsports-2019-101242Mota-Pereira J, Silverio J, Carvalho S, Ribeiro JC, Fonte D, Ramos J.Moderate exercise improves depression parameters in treatment-resistant patients with major depressive disorder. J Psychiatr Res. 2011;45(8):1005-1011. DOI: 10.1016/j.jpsychires.2011.02.005Bookworms versus nerds: Exposure to fiction versus non-fiction, divergent associations with social ability, and the simulation of fictional social worlds.Journal of Research in Personality. 2006;40(5):694-712. DOI: 10.1016/j.jrp.2005.08.002Gualano MR, Bert F, Martorana M, et al.The long-term effects of bibliotherapy in depression treatment: Systematic review of randomized clinical trials. Clinical Psychology Review. 2017;58:49-58. DOI: 10.1016/j.cpr.2017.09.006Krpan KM, Kross E, Berman MG, Deldin PJ, Askren MK, Jonides J.An everyday activity as a treatment for depression: The benefits of expressive writing for people diagnosed with major depressive disorder. J Affect Disord. 2013;150(3):1148-1151. DOI: 10.1016/j.jad.2013.05.065Yang L, Zhao Y, Wang Y, et al.The effects of psychological stress on depression. Curr Neuropharmacol. 2015;13(4):494-504. DOI: 10.2174/1570159X1304150831150507

Wiles N, Williams CJ, Kessler D, Lewis G.Psychological therapies for treatment-resistant depression in adults. Cochrane Common Mental Disorders Group, ed. Cochrane Database of Systematic Reviews. DOI: 10.1002/14651858.CD010558.pub2

Markowitz JC, Wright JH, Peeters F, Thase ME, Kocsis JH, Sudak DM.The neglected role of psychotherapy for treatment-resistant depression. AJP. 2022;179(2):90-93. DOI: 10.1176/appi.ajp.2021.21050535

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

Abbass AA.Intensive Short-Term Dynamic Psychotherapy of treatment-resistant depression: a pilot study. Depress Anxiety. 2006;23(7):449-452. DOI: 10.1002/da.20203

Al-Harbi KS.Treatment-resistant depression: therapeutic trends, challenges, and future directions. Patient Prefer Adherence. 2012;6:369-388. DOI: 10.2147/PPA.S29716

Goodwin GM, Aaronson ST, Alvarez O, et al.Single-dose psilocybin for a treatment-resistant episode of major depression.N Engl J Med. 2022;387(18):1637-1648. DOI: 10.1056/NEJMoa2206443

Cole EJ, Stimpson KH, Bentzley BS, et al.Stanford accelerated intelligent neuromodulation therapy for treatment-resistant depression.AJP. 2020;177(8):716-726. DOI: 10.1176/appi.ajp.2021.20101429

Pycroft L, Stein J, Aziz T.Deep brain stimulation: An overview of history, methods, and future developments. Brain and Neuroscience Advances. 2018;2:239821281881601. DOI: 10.1177/2398212818816017

Brus O, Cao Y, Gustafsson E, et al.Self-assessed remission rates after electroconvulsive therapy of depressive disorders. Eur psychiatr. 2017;45:154-160. DOI: 10.1016/j.eurpsy.2017.06.015

Deane KHO, Jimoh OF, Biswas P, et al.Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials. The British Journal of Psychiatry. 2021;218(3):135-142. DOI: 10.1192/bjp.2019.234

Iovieno N, Dalton ED, Fava M, Mischoulon D.Second-tier natural antidepressants: Review and critique. Journal of Affective Disorders. 2011;130(3):343-357. DOI: 10.1016/j.jad.2010.06.010

Dome P, Tombor L, Lazary J, Gonda X, Rihmer Z.Natural health products, dietary minerals and over-the-counter medications as add-on therapies to antidepressants in the treatment of major depressive disorder: a review. Brain Research Bulletin. 2019;146:51-78. DOI: 10.1016/j.brainresbull.2018.12.015

Smith CA, Armour M, Lee MS, Wang LQ, Hay PJ.Acupuncture for depression. Cochrane Database of Systematic Reviews. 2018;(3). DOI: 10.1002/14651858.CD004046.pub4.

Brinsley J, Schuch F, Lederman O, et al.Effects of yoga on depressive symptoms in people with mental disorders: a systematic review and meta-analysis. Br J Sports Med. 2021;55(17):992-1000. DOI: 10.1136/bjsports-2019-101242

Mota-Pereira J, Silverio J, Carvalho S, Ribeiro JC, Fonte D, Ramos J.Moderate exercise improves depression parameters in treatment-resistant patients with major depressive disorder. J Psychiatr Res. 2011;45(8):1005-1011. DOI: 10.1016/j.jpsychires.2011.02.005

Bookworms versus nerds: Exposure to fiction versus non-fiction, divergent associations with social ability, and the simulation of fictional social worlds.Journal of Research in Personality. 2006;40(5):694-712. DOI: 10.1016/j.jrp.2005.08.002

Gualano MR, Bert F, Martorana M, et al.The long-term effects of bibliotherapy in depression treatment: Systematic review of randomized clinical trials. Clinical Psychology Review. 2017;58:49-58. DOI: 10.1016/j.cpr.2017.09.006

Krpan KM, Kross E, Berman MG, Deldin PJ, Askren MK, Jonides J.An everyday activity as a treatment for depression: The benefits of expressive writing for people diagnosed with major depressive disorder. J Affect Disord. 2013;150(3):1148-1151. DOI: 10.1016/j.jad.2013.05.065

Yang L, Zhao Y, Wang Y, et al.The effects of psychological stress on depression. Curr Neuropharmacol. 2015;13(4):494-504. DOI: 10.2174/1570159X1304150831150507

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Cognitive Therapies#

Complementary Alternative Medicine (CAM) & Over-the-Counter (OTC)#

Diet#

Exercise#

Things You Can Try on Your Own#

How to Make Your Treatment Most Effective#

Medication Adherence#

Avoid Alcohol and Other Drugs#

Minimize Stress#

Consider Cost#