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Raw Queries and Responses

1. Shard Calculation

Query:

Response:

Calculated Shard: 61 (from laksa117)

2. Crawled Status Check

Query:

curl -X POST \
  'http://laksa061.int.ahrefs:8124/' \
  -H 'Content-Type: text/plain' \
  -H 'X-ClickHouse-Database: crawler3' \
  -H 'Authorization: Basic YXBpOg==' \
  -d 'SELECT getAhrefsURLFromUnparsed(src_unparsed) AS found_url, ifNull(toUnixTimestamp(download_stamp), 0) AS crawl_time, ifNull(toUnixTimestamp(props_url_first_seen), 0) AS first_indexed_time, download_http_code AS http_code, src_unparsed AS src_unparsed, src_root_hash AS src_root_hash, history_drop_reason AS history_drop_reason, meta_title AS meta_title, meta_descriptions AS meta_descriptions, attrs_boilerpipe_text AS attrs_boilerpipe_text, attrs_markdown AS attrs_markdown, attrs_readable_markdown AS attrs_readable_markdown, meta_canonical AS meta_canonical FROM crawler3.page_info_local FINAL PREWHERE (src_root_hash, src_unparsed) IN ((getAhrefsRootHashFromUnparsed(getAhrefsUnparsedNoserviceFromURL(\'https://www.goodrx.com/conditions/depression/treatment-resistant-depression\')), getAhrefsUnparsedNoserviceFromURL(\'https://www.goodrx.com/conditions/depression/treatment-resistant-depression\'))) FORMAT JSONEachRow'

Response:

{"found_url":"https:\/\/www.goodrx.com\/conditions\/depression\/treatment-resistant-depression","crawl_time":1775361085,"first_indexed_time":0,"http_code":200,"src_unparsed":"com,goodrx!www,\/conditions\/depression\/treatment-resistant-depression s443","src_root_hash":"16240351626176129661","history_drop_reason":null,"meta_title":"Treatment-Resistant Depression: Treatment Options to Know - GoodRx","meta_descriptions":["An antidepressant isn’t always enough to ease the symptoms of depression. If you have treatment-resistant depression, there are many treatment options out there."],"attrs_boilerpipe_text":"Key takeaways:\nIf you still feel depressed after trying antidepressants, you may have something called treatment-resistant depression.\nThough the name may sound discouraging, treatment-resistant depression is treatable.\nThere are many therapies that can help with treatment-resistant depression. These include medications and nonmedication options.\nHave you been told that you have treatment-resistant depression? This is a term used by some healthcare professionals that can be confusing and disheartening. You may think it means that you have depression that won’t get any better. But that’s not the case at all. It just means it’s time to try something else. And you actually have many different treatment options that can help this kind of depression.\nTreatment-resistant depression refers to symptoms of depression that are ongoing even with treatment. These treatments are usually antidepressant medications. \nBut the term “treatment-resistant depression” isn’t very useful for people with depression or even for healthcare professionals. That’s because experts don’t agree on the exact\ndefinition\n. Some say it’s depression that persists after a period of taking just one medication. Others say it should be diagnosed after two or three failed medication trials. \nAlso, people can feel like the term means that their depression will never get better. They may start to lose hope after trying medications that weren’t too helpful for them. In reality,\nmany people\ndon’t feel much better after their first or second antidepressant. \nDepression can be hard to treat, for many reasons: \nEveryone has a unique brain that doesn’t react the same way to medication. Certain medications can be really helpful for one person and not for another, and no one knows why. \nMedication can cause side effects that can make a person feel bad, like\nweight gain\nor\nsexual side effects\n. These can happen even if the medication is helping the original depression. So this can make it hard to know if the medication is helping.\nThere are many factors in life that affect people’s moods. Medication doesn’t address social problems or lifestyle factors that can worsen depression.\nBut treatment-resistant depression can improve with ongoing treatment. Theresa Toledo, MD, is a psychiatrist in southeast Michigan who works with mood disorders including depression. She said that “treatment-resistant does not imply that depression cannot get better.” \nYou and your healthcare team may want to look at different options for treatment. This can start with a change in medications.\nNearly every day\nMore than half the days\nSeveral days\nNot at all\nIn the past 2 weeks, have you felt down, depressed, or hopeless:\nNearly every day\nMore than half the days\nSeveral days\nNot at all\nIn the past 2 weeks, have you had trouble falling asleep, staying asleep, or sleeping too much:\nNearly every day\nMore than half the days\nSeveral days\nNot at all\nIn the past 2 weeks, have you felt tired or had little energy:\nNearly every day\nMore than half the days\nSeveral days\nNot at all\nIn the past 2 weeks, have you had a poor appetite or overeaten:\nNearly every day\nMore than half the days\nSeveral days\nNot at all\nIn the past 2 weeks, have you felt bad about yourself — or that you’re a failure, or have let yourself or your family down:\nNearly every day\nMore than half the days\nSeveral days\nNot at all\nIn the past 2 weeks, have you had trouble concentrating on things, like reading or watching television:\nNearly every day\nMore than half the days\nSeveral days\nNot at all\nIn the past 2 weeks, have you either been so slowed down or so restless that other people could have noticed:\nNearly every day\nMore than half the days\nSeveral days\nNot at all\nIn the past 2 weeks, have you had thoughts about hurting yourself in some way, or that you would be better off dead:\nNearly every day\nMore than half the days\nSeveral days\nNot at all\nSeveral kinds of medications can be useful for treatment-resistant depression. Switching to a different antidepressant can be helpful. And other types of medications can enhance the effects of an antidepressant. It’s common to use a combination of medications for treatment-resistant depression.\nThe most common medications used for depression are\nselective serotonin reuptake inhibitors\n(SSRIs). And even though they are called antidepressants, SSRIs are also prescribed for anxiety. There are several different SSRIs, and one of them may work better for you than another. \nCommon SSRIs include:\nCompare prices and information on the most popular Depression medications.\nSerotonin and norepinephrine reuptake inhibitors\n(SNRIs) are another kind of antidepressant. Like SSRIs, SNRIs affect\nserotonin\nin the brain, which helps to regulate mood. But they also affect\nnorepinephrine\n. Because of this, SNRIs can be helpful for chronic pain and anxiety, too.\nCommon SNRIs include:\nThere are other kinds of antidepressants that work on slightly different brain chemicals: \nVortioxetine\n(Trintellix) and\nvilazodone\n(Viibryd) are similar to SSRIs. But they also affect different serotonin brain receptors.\nMirtazapine\n(Remeron) is an antidepressant that also affects histamine. This can be helpful for sleep. \nBupropion\n(Wellbutrin SR, Wellbutrin XL) affects norepinephrine and dopamine. It can sometimes double as a\ntreatment for ADHD\n(attention-deficit hyperactivity disorder).\nAuvelity\nis a newer antidepressant that’s a combination of two medications — dextromethorphan and bupropion. Dextromethorphan affects a specific receptor in the brain called the NMDA receptor. \nAdding\nantipsychotic medications\nto antidepressants can also be helpful for treatment-resistant depression. These are usually used to treat conditions such as\nbipolar disorder\nand\nschizophrenia\n. But\nlower doses\nof these medications can be helpful in depression. \nThe FDA has approved these antipsychotics as medications for depression:\nAripiprazole\n(Abilify)\nBrexpiprazole\n(Rexulti)\nCariprazine\n(Vraylar)\nOlanzapine\n(Zyprexa)\nQuetiapine\n(Seroquel)\nSymbyax\n(Olanzapine\/fluoxetine)\nThere are other\nkinds of medications\n— beyond antidepressants and antipsychotics — that have also been shown to be helpful for treatment-resistant depression. \nSpravato\n(esketamine) is a newer medication that’s FDA approved for treatment-resistant depression. It’s a form of ketamine, which is an IV medication that’s sometimes used as a\ntype of anesthesia\n. The IV form of ketamine is also used for\noff-label treatment\nfor treatment-resistant depression. But Spravato is a nasal spray that you can receive in a healthcare office. This is so your healthcare team can watch for potential side effects for a couple of hours after each dose.\nThere are other medications that are sometimes used in addition to more common depression treatments. But it’s important to note that they aren’t officially FDA approved for depression. Because of this, they are only used in specific circumstances and with the guidance of an experienced healthcare professional:\nLithium\nis usually used for stabilizing mood in bipolar disorder. It can improve mood in treatment-resistant depression, too. But blood levels need to be checked during treatment to prevent possible\nlithium toxicity\n.\nThyroid hormone\n(\nlevothyroxine\n) can also be added to antidepressants. Your prescriber will want to track your thyroid function while you’re taking this hormone.\nLlisdexamfetamine (\nVyvanse\n) is a stimulant medication usually used for ADHD. It has also been shown to be helpful as an add-on for depression.\nBuspirone\n(Buspar) is a medication that can sometimes be used to treat anxiety.\nTreatments other than medications have proved helpful for treatment-resistant depression. \nStudies show that\npsychotherapy\nis helpful for treatment-resistant depression. The most helpful kinds of therapy for treatment-resistant depression are:\nCognitive behavioral therapy (CBT):\nThis well-known therapy helps you understand how you think, behave, and feel.\nCBT\nhelps you recognize and make changes to thinking patterns that contribute to depression.\nInterpersonal therapy:\nThis kind of therapy focuses on making relationships better. \nMindfulness-based cognitive therapy:\nLearning how to be present in the moment is a helpful way to understand and ease symptoms of depression and anxiety.\nTalking to a therapist is often an important part of treating depression. Therapy can help you change your mindset and the ways you go about your life. It can help you think about things differently. You may have tried therapy and felt it was not helpful. But try not to get discouraged. It may just mean you need to keep looking until you\nfind a therapist\nwho is the right fit for you.\nElectroconvulsive therapy\n(ECT) is a depression treatment that uses controlled seizures. This may sound scary, but it can actually be quite effective. In fact, ECT has been named the “gold standard” for treating treatment-resistant depression. \nFirst, the person receives anesthetic medication so that they are relaxed and not aware of the seizure. Then a healthcare professional uses an electrical charge to the scalp to start a brief seizure. Since the person is asleep, this isn’t painful. The treatment is repeated over a period of several weeks or months. It’s an outpatient procedure and considered to be safer than surgery. \nTranscranial magnetic stimulation\n(TMS) is another procedure that can help treatment-resistant depression. A magnetic coil is placed on the scalp in a medical office. An electrical current is passed through a part of the brain. Like ECT, this is not painful. This procedure is also repeated over the course of several weeks.\nVagal nerve stimulation (VNS) uses an electrical stimulator in the body to activate the vagus nerve. The vagus nerve is a large nerve in the body that’s important in the parasympathetic nervous system. This is the part of the nervous system that helps the body rest and relax. \nThis treatment requires a small procedure. A surgeon implants the stimulator in the neck, where the nerve is located. It treats both treatment-resistant depression and epilepsy.\nDepression has a way of making people neglect themselves. When you take time to do things you used to enjoy, even if you don’t want to at the moment, it can help your mood. Also, taking care of yourself is part of the bigger picture in your depression treatment. \n“I always emphasize there are three important things we do for mental health treatment,” Toledo said. Those are: \nMedication\nPsychotherapy\nOverall health and habits, including sleep, diet, and exercise \nStudies show that\nexercise\ncan be helpful for treatment-resistant depression. Many people with depression have a\nhard time getting motivated to exercise\n. But research shows that exercise helps people with depression who are already taking an antidepressant. And every little bit helps. This can be as simple as moving and stretching your body more in your daily routines.\nDepression can feel worse when you feel physically down, too. Changing your diet and drinking enough water may help you feel better. Foods with fiber, protein, and complex carbohydrates will help to maintain your metabolism. \nResearch on the\ngut-brain connection\nis becoming more common. This term describes how the nerves of the stomach and intestines are related to the brain. Keeping the gut healthy could help your mental health.\nPeople with depression are more likely to isolate themselves from others and experience loneliness. But research shows that increased\nsocial interaction\ncan help with mood and loneliness. It may be difficult to be social, but spending time with loved ones — or even people you don’t know very well — can help lift you up.\nLook at your relationships to see if you are stuck in an unhealthy rut. Sometimes, people don’t realize how much their relationships affect their mood. These unhealthy relationships can be with partners, family, friends, or colleagues. Therapy is a good setting to work through your feelings about relationships.\nDon’t neglect your physical health when focused on treating your depression. Toledo also noted that it’s important to get a checkup with your primary care provider. “Maintaining overall health is important,” she said. “Your primary care provider can rule out conditions that can make depression worse. Examples are anemia, diabetes, and thyroid disease.”\nThe bottom line\nTreatment-resistant depression doesn’t mean that your depression is untreatable. Trying different medications or combinations is an option. Depression can improve with therapy, exercise, and other lifestyle strategies. If you’ve heard the term “treatment resistant” describe your depression, don’t give up hope on feeling better. Many times, it’s just a matter of finding the right treatment formula that works best for you.\nKatherine Krive, DO, is a freelance medical writer and editor. She is also a psychiatrist who has practiced in hospital, academic, and community settings.\nKatie E. Golden, MD, is a board-certified emergency medicine physician and a medical editor at GoodRx.\nJoshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.\nGoodRx Health has strict sourcing policies and relies on primary sources such as medical organizations, governmental agencies, academic institutions, and peer-reviewed scientific journals. Learn more about how we ensure our content is accurate, thorough, and unbiased by reading our\neditorial guidelines\n.","attrs_markdown":"[Skip to main content](https:\/\/www.goodrx.com\/conditions\/depression\/treatment-resistant-depression#skip-to-content)\n\nAre you a healthcare professional? 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[Home](https:\/\/www.goodrx.com\/health)\n2. [Health Conditions](https:\/\/www.goodrx.com\/conditions)\n3. [Depression](https:\/\/www.goodrx.com\/conditions\/depression)\n\nDepression\n\n# What Are Your Options If You Have Treatment-Resistant Depression?\n\n[![Katherine Krive, DO](https:\/\/www.grxstatic.com\/4f3rgqwzdznj\/1dm4QxniN8Pv1FV29c1G3Z\/63b503548e50e254d09785aed218d70d\/Headshot.png?w=96&q=85&fm=webp)](https:\/\/www.goodrx.com\/about\/bio\/katherine-krive)[![Katie E. Golden, MD](https:\/\/www.grxstatic.com\/4f3rgqwzdznj\/491qgaKVwSdYx6oA4WaGQw\/fba8bf9652d561990e7b612874ad74d6\/katie_golden_goodrx.webp?w=96&q=85&fm=webp)](https:\/\/www.goodrx.com\/about\/bio\/katie-golden)\n\nWritten by [Katherine Krive, DO](https:\/\/www.goodrx.com\/about\/bio\/katherine-krive) \\| Reviewed by [Katie E. Golden, MD](https:\/\/www.goodrx.com\/about\/bio\/katie-golden), [Joshua Murdock, PharmD, BCBBS](https:\/\/www.goodrx.com\/about\/bio\/joshua-murdock)\n\nUpdated on April 1, 2025\n\n![star](https:\/\/www.grxstatic.com\/images\/star-with-circle.svg)![A sad client being offered a tissue box by their therapist.](https:\/\/www.grxstatic.com\/4f3rgqwzdznj\/434TqLhXmZw370jwseV0DY\/70e43895d22b11b470513ccaa64f9a2e\/offered_tissue_box_by_therapist_1436884593.jpg?w=3840&q=99&fm=webp)\n\nAnnaStills\/iStock via Getty Images Plus\n\n[Definition](https:\/\/www.goodrx.com\/conditions\/depression\/treatment-resistant-depression#definition)[Quiz](https:\/\/www.goodrx.com\/conditions\/depression\/treatment-resistant-depression#quiz)[Medication](https:\/\/www.goodrx.com\/conditions\/depression\/treatment-resistant-depression#medication)[Other treatments](https:\/\/www.goodrx.com\/conditions\/depression\/treatment-resistant-depression#other-treatments)[Self-care tips](https:\/\/www.goodrx.com\/conditions\/depression\/treatment-resistant-depression#self-care-tips)[Bottom line](https:\/\/www.goodrx.com\/conditions\/depression\/treatment-resistant-depression#bottom-line)[References](https:\/\/www.goodrx.com\/conditions\/depression\/treatment-resistant-depression#references)\n\n## Key takeaways:\n- If you still feel depressed after trying antidepressants, you may have something called treatment-resistant depression.\n- Though the name may sound discouraging, treatment-resistant depression is treatable.\n- There are many therapies that can help with treatment-resistant depression. These include medications and nonmedication options.\n\nHave you been told that you have treatment-resistant depression? This is a term used by some healthcare professionals that can be confusing and disheartening. You may think it means that you have depression that won’t get any better. But that’s not the case at all. It just means it’s time to try something else. And you actually have many different treatment options that can help this kind of depression.\n\n## What is treatment-resistant depression?\nTreatment-resistant depression refers to symptoms of depression that are ongoing even with treatment. These treatments are usually antidepressant medications.\n\nBut the term “treatment-resistant depression” isn’t very useful for people with depression or even for healthcare professionals. That’s because experts don’t agree on the exact [definition](https:\/\/pubmed.ncbi.nlm.nih.gov\/31638723\/). Some say it’s depression that persists after a period of taking just one medication. Others say it should be diagnosed after two or three failed medication trials.\n\nAlso, people can feel like the term means that their depression will never get better. They may start to lose hope after trying medications that weren’t too helpful for them. In reality, [many people](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4761633\/) don’t feel much better after their first or second antidepressant.\n\nDepression can be hard to treat, for many reasons:\n\n- Everyone has a unique brain that doesn’t react the same way to medication. Certain medications can be really helpful for one person and not for another, and no one knows why.\n- Medication can cause side effects that can make a person feel bad, like [weight gain](https:\/\/www.goodrx.com\/conditions\/depression\/antidepressants-weight-gain) or [sexual side effects](https:\/\/www.goodrx.com\/drugs\/side-effects\/these-drugs-may-be-affecting-your-sex-life#antidepressants). These can happen even if the medication is helping the original depression. So this can make it hard to know if the medication is helping.\n- There are many factors in life that affect people’s moods. Medication doesn’t address social problems or lifestyle factors that can worsen depression.\n\nBut treatment-resistant depression can improve with ongoing treatment. Theresa Toledo, MD, is a psychiatrist in southeast Michigan who works with mood disorders including depression. She said that “treatment-resistant does not imply that depression cannot get better.”\n\nYou and your healthcare team may want to look at different options for treatment. This can start with a change in medications.\n\n## Quiz: Is your antidepressant working?\nIn the past 2 weeks, have you had little interest or pleasure in doing things:\n\n- Nearly every day\n- More than half the days\n- Several days\n- Not at all\n\n### In the past 2 weeks, have you felt down, depressed, or hopeless:\n- Nearly every day\n- More than half the days\n- Several days\n- Not at all\n\n### In the past 2 weeks, have you had trouble falling asleep, staying asleep, or sleeping too much:\n- Nearly every day\n- More than half the days\n- Several days\n- Not at all\n\n### In the past 2 weeks, have you felt tired or had little energy:\n- Nearly every day\n- More than half the days\n- Several days\n- Not at all\n\n### In the past 2 weeks, have you had a poor appetite or overeaten:\n- Nearly every day\n- More than half the days\n- Several days\n- Not at all\n\n### In the past 2 weeks, have you felt bad about yourself — or that you’re a failure, or have let yourself or your family down:\n- Nearly every day\n- More than half the days\n- Several days\n- Not at all\n\n### In the past 2 weeks, have you had trouble concentrating on things, like reading or watching television:\n- Nearly every day\n- More than half the days\n- Several days\n- Not at all\n\n### In the past 2 weeks, have you either been so slowed down or so restless that other people could have noticed:\n- Nearly every day\n- More than half the days\n- Several days\n- Not at all\n\n### In the past 2 weeks, have you had thoughts about hurting yourself in some way, or that you would be better off dead:\n- Nearly every day\n- More than half the days\n- Several days\n- Not at all\n\n## What medications can help treatment-resistant depression?\nSeveral kinds of medications can be useful for treatment-resistant depression. Switching to a different antidepressant can be helpful. And other types of medications can enhance the effects of an antidepressant. It’s common to use a combination of medications for treatment-resistant depression.\n\n![GoodRx icon](https:\/\/www.grxstatic.com\/images\/goodrx-logo.svg)\n\nEXPERT PICKS: WHAT TO READ NEXT\n\n- **Treating depression with psilocybin:** Psychedelic substances like magic mushrooms are emerging as a new treatment for depression. Learn more about [how it works](https:\/\/www.goodrx.com\/conditions\/depression\/psilocybin-and-depression).\n- **Does magnesium help with anxiety?** There’s some research to suggest [magnesium supplements](https:\/\/www.goodrx.com\/well-being\/supplements-herbs\/magnesium-for-anxiety) can help with anxiety, depression, and trouble sleeping.\n- **IV ketamine vs. Spravato:** If you have hard-to-treat depression, ketamine may help. But it’s important to understand the [main differences in these two forms](https:\/\/www.goodrx.com\/conditions\/depression\/iv-ketamine-vs-spravato).\n\n### Antidepressants\nThe most common medications used for depression are [selective serotonin reuptake inhibitors](https:\/\/www.goodrx.com\/classes\/ssris\/ssri-list) (SSRIs). And even though they are called antidepressants, SSRIs are also prescribed for anxiety. There are several different SSRIs, and one of them may work better for you than another.\n\nCommon SSRIs include:\n\n- [Citalopram](https:\/\/www.goodrx.com\/citalopram\/what-is) (Celexa)\n- [Escitalopram](https:\/\/www.goodrx.com\/lexapro\/what-is) (Lexapro)\n- [Fluoxetine](https:\/\/www.goodrx.com\/prozac\/what-is) (Prozac)\n- [Paroxetine](https:\/\/www.goodrx.com\/paroxetine\/what-is) (Paxil)\n- [Sertraline](https:\/\/www.goodrx.com\/zoloft\/what-is) (Zoloft)\n\nPromotion disclosure\n\nDepression medicationsCompare prices and information on the most popular Depression medications.\n\n- Lexapro\n  \n  Escitalopram\n  \n  \\$11.47Lowest price\n  \n  [Save now](https:\/\/www.goodrx.com\/lexapro)\n- Prozac\n  \n  Fluoxetine\n  \n  \\$9.00Lowest price\n  \n  [Save now](https:\/\/www.goodrx.com\/prozac)\n- Zoloft\n  \n  Sertraline\n  \n  \\$12.01Lowest price\n  \n  [Save now](https:\/\/www.goodrx.com\/zoloft)\n\n[Compare all medications](https:\/\/www.goodrx.com\/conditions\/depression\/drugs)\n\n[Serotonin and norepinephrine reuptake inhibitors](https:\/\/www.goodrx.com\/classes\/snris\/snri-drugs-list) (SNRIs) are another kind of antidepressant. Like SSRIs, SNRIs affect [serotonin](https:\/\/www.goodrx.com\/health-topic\/hormones\/serotonin) in the brain, which helps to regulate mood. But they also affect [norepinephrine](https:\/\/www.goodrx.com\/classes\/snris\/snri-side-effects). Because of this, SNRIs can be helpful for chronic pain and anxiety, too.\n\nCommon SNRIs include:\n\n- [Desvenlafaxine](https:\/\/www.goodrx.com\/desvenlafaxine-succinate-er\/what-is) (Pristiq)\n- [Duloxetine](https:\/\/www.goodrx.com\/cymbalta\/what-is) (Cymbalta)\n- [Levomilnacipran](https:\/\/www.goodrx.com\/fetzima\/what-is) (Fetzima)\n- [Venlafaxine](https:\/\/www.goodrx.com\/venlafaxine\/what-is) (Effexor XR)\n\nThere are other kinds of antidepressants that work on slightly different brain chemicals:\n\n- [Vortioxetine](https:\/\/www.goodrx.com\/trintellix\/what-is) (Trintellix) and [vilazodone](https:\/\/www.goodrx.com\/viibryd\/what-is) (Viibryd) are similar to SSRIs. But they also affect different serotonin brain receptors.\n- [Mirtazapine](https:\/\/www.goodrx.com\/mirtazapine\/what-is) (Remeron) is an antidepressant that also affects histamine. This can be helpful for sleep.\n- [Bupropion](https:\/\/www.goodrx.com\/bupropion\/what-is) (Wellbutrin SR, Wellbutrin XL) affects norepinephrine and dopamine. It can sometimes double as a [treatment for ADHD](https:\/\/www.goodrx.com\/wellbutrin\/how-it-works) (attention-deficit hyperactivity disorder).\n- [Auvelity](https:\/\/www.goodrx.com\/auvelity\/what-is) is a newer antidepressant that’s a combination of two medications — dextromethorphan and bupropion. Dextromethorphan affects a specific receptor in the brain called the NMDA receptor.\n\n### Antipsychotics\nAdding [antipsychotic medications](https:\/\/www.goodrx.com\/health-topic\/mental-health\/typical-vs-atypical-antipsychotics) to antidepressants can also be helpful for treatment-resistant depression. These are usually used to treat conditions such as [bipolar disorder](https:\/\/www.goodrx.com\/conditions\/bipolar-disorder) and [schizophrenia](https:\/\/www.goodrx.com\/conditions\/schizophrenia). But [lower doses](https:\/\/psychiatryonline.org\/pb\/assets\/raw\/sitewide\/practice_guidelines\/guidelines\/mdd-1410197717630.pdf) of these medications can be helpful in depression.\n\nThe FDA has approved these antipsychotics as medications for depression:\n\n- [Aripiprazole](https:\/\/www.goodrx.com\/aripiprazole\/what-is) (Abilify)\n- [Brexpiprazole](https:\/\/www.goodrx.com\/rexulti\/what-is) (Rexulti)\n- [Cariprazine](https:\/\/www.goodrx.com\/vraylar\/what-is) (Vraylar)\n- [Olanzapine](https:\/\/www.goodrx.com\/olanzapine\/what-is) (Zyprexa)\n- [Quetiapine](https:\/\/www.goodrx.com\/quetiapine\/what-is) (Seroquel)\n- [Symbyax](https:\/\/www.goodrx.com\/symbyax\/what-is) (Olanzapine\/fluoxetine)\n\n### Other medications for treatment-resistant depression\nThere are other [kinds of medications](https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0165032721014518?via%3Dihub) — beyond antidepressants and antipsychotics — that have also been shown to be helpful for treatment-resistant depression.\n\n[Spravato](https:\/\/www.goodrx.com\/spravato\/what-is) (esketamine) is a newer medication that’s FDA approved for treatment-resistant depression. It’s a form of ketamine, which is an IV medication that’s sometimes used as a [type of anesthesia](https:\/\/www.goodrx.com\/conditions\/anesthesia\/types-of-anesthesia). The IV form of ketamine is also used for [off-label treatment](https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0165178124001501) for treatment-resistant depression. But Spravato is a nasal spray that you can receive in a healthcare office. This is so your healthcare team can watch for potential side effects for a couple of hours after each dose.\n\nThere are other medications that are sometimes used in addition to more common depression treatments. But it’s important to note that they aren’t officially FDA approved for depression. Because of this, they are only used in specific circumstances and with the guidance of an experienced healthcare professional:\n\n- [Lithium](https:\/\/www.goodrx.com\/lithium\/what-is) is usually used for stabilizing mood in bipolar disorder. It can improve mood in treatment-resistant depression, too. But blood levels need to be checked during treatment to prevent possible [lithium toxicity](https:\/\/www.goodrx.com\/lithium\/what-lithium-side-effects-should-you-expect#lithium-toxicity).\n- [Thyroid hormone](https:\/\/www.goodrx.com\/synthroid\/what-is) ([levothyroxine](https:\/\/www.goodrx.com\/synthroid\/what-is)) can also be added to antidepressants. Your prescriber will want to track your thyroid function while you’re taking this hormone.\n- Llisdexamfetamine ([Vyvanse](https:\/\/www.goodrx.com\/vyvanse\/what-is)) is a stimulant medication usually used for ADHD. It has also been shown to be helpful as an add-on for depression.\n- [Buspirone](https:\/\/www.goodrx.com\/buspirone\/what-is) (Buspar) is a medication that can sometimes be used to treat anxiety.\n\n## What are other treatment options for treatment-resistant depression?\nTreatments other than medications have proved helpful for treatment-resistant depression.\n\n### Psychotherapy\nStudies show that [psychotherapy](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6982454\/) is helpful for treatment-resistant depression. The most helpful kinds of therapy for treatment-resistant depression are:\n\n- **Cognitive behavioral therapy (CBT):** This well-known therapy helps you understand how you think, behave, and feel. [CBT](https:\/\/www.goodrx.com\/health-topic\/mental-health\/cognitive-behavioral-therapy) helps you recognize and make changes to thinking patterns that contribute to depression.\n- **Interpersonal therapy:** This kind of therapy focuses on making relationships better.\n- **Mindfulness-based cognitive therapy:** Learning how to be present in the moment is a helpful way to understand and ease symptoms of depression and anxiety.\n\nTalking to a therapist is often an important part of treating depression. Therapy can help you change your mindset and the ways you go about your life. It can help you think about things differently. You may have tried therapy and felt it was not helpful. But try not to get discouraged. It may just mean you need to keep looking until you [find a therapist](https:\/\/www.goodrx.com\/health-topic\/mental-health\/psychiatrist-vs-psychologist) who is the right fit for you.\n\n### ECT\n[Electroconvulsive therapy](https:\/\/www.goodrx.com\/conditions\/depression\/depression-ect) (ECT) is a depression treatment that uses controlled seizures. This may sound scary, but it can actually be quite effective. In fact, ECT has been named the “gold standard” for treating treatment-resistant depression.\n\nFirst, the person receives anesthetic medication so that they are relaxed and not aware of the seizure. Then a healthcare professional uses an electrical charge to the scalp to start a brief seizure. Since the person is asleep, this isn’t painful. The treatment is repeated over a period of several weeks or months. It’s an outpatient procedure and considered to be safer than surgery.\n\n### TMS\n[Transcranial magnetic stimulation](https:\/\/www.psychologytoday.com\/us\/basics\/transcranial-magnetic-stimulation-therapy) (TMS) is another procedure that can help treatment-resistant depression. A magnetic coil is placed on the scalp in a medical office. An electrical current is passed through a part of the brain. Like ECT, this is not painful. This procedure is also repeated over the course of several weeks.\n\n### VNS\nVagal nerve stimulation (VNS) uses an electrical stimulator in the body to activate the vagus nerve. The vagus nerve is a large nerve in the body that’s important in the parasympathetic nervous system. This is the part of the nervous system that helps the body rest and relax.\n\nThis treatment requires a small procedure. A surgeon implants the stimulator in the neck, where the nerve is located. It treats both treatment-resistant depression and epilepsy.\n\n## Self-care tips for treatment-resistant depression\nDepression has a way of making people neglect themselves. When you take time to do things you used to enjoy, even if you don’t want to at the moment, it can help your mood. Also, taking care of yourself is part of the bigger picture in your depression treatment.\n\n“I always emphasize there are three important things we do for mental health treatment,” Toledo said. Those are:\n\n- Medication\n- Psychotherapy\n- Overall health and habits, including sleep, diet, and exercise\n\n### Exercise\nStudies show that [exercise](https:\/\/www.cambridge.org\/core\/journals\/cns-spectrums\/article\/abs\/exercise-as-an-addon-strategy-for-the-treatment-of-major-depressive-disorder-a-systematic-review\/879856D988F804EE03393226324BA176) can be helpful for treatment-resistant depression. Many people with depression have a [hard time getting motivated to exercise](https:\/\/www.goodrx.com\/well-being\/movement-exercise\/working-out-tired). But research shows that exercise helps people with depression who are already taking an antidepressant. And every little bit helps. This can be as simple as moving and stretching your body more in your daily routines.\n\n### Eating well\nDepression can feel worse when you feel physically down, too. Changing your diet and drinking enough water may help you feel better. Foods with fiber, protein, and complex carbohydrates will help to maintain your metabolism.\n\nResearch on the [gut-brain connection](https:\/\/www.goodrx.com\/health-topic\/mental-health\/brain-gut-connection) is becoming more common. This term describes how the nerves of the stomach and intestines are related to the brain. Keeping the gut healthy could help your mental health.\n\n### Socializing\nPeople with depression are more likely to isolate themselves from others and experience loneliness. But research shows that increased [social interaction](https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/02654075211045717) can help with mood and loneliness. It may be difficult to be social, but spending time with loved ones — or even people you don’t know very well — can help lift you up.\n\n### Relationships\nLook at your relationships to see if you are stuck in an unhealthy rut. Sometimes, people don’t realize how much their relationships affect their mood. These unhealthy relationships can be with partners, family, friends, or colleagues. Therapy is a good setting to work through your feelings about relationships.\n\n### Regular healthcare visits\nDon’t neglect your physical health when focused on treating your depression. Toledo also noted that it’s important to get a checkup with your primary care provider. “Maintaining overall health is important,” she said. “Your primary care provider can rule out conditions that can make depression worse. Examples are anemia, diabetes, and thyroid disease.”\n\n## The bottom line\nTreatment-resistant depression doesn’t mean that your depression is untreatable. Trying different medications or combinations is an option. Depression can improve with therapy, exercise, and other lifestyle strategies. If you’ve heard the term “treatment resistant” describe your depression, don’t give up hope on feeling better. Many times, it’s just a matter of finding the right treatment formula that works best for you.\n\n![why trust our exports reliability shield](https:\/\/www.grxstatic.com\/images\/reliability.svg)\n\n## Why trust our experts?\n\n![Katherine Krive, DO](https:\/\/images.ctfassets.net\/4f3rgqwzdznj\/1dm4QxniN8Pv1FV29c1G3Z\/63b503548e50e254d09785aed218d70d\/Headshot.png)\n\n![Katherine Krive, DO](https:\/\/images.ctfassets.net\/4f3rgqwzdznj\/1dm4QxniN8Pv1FV29c1G3Z\/63b503548e50e254d09785aed218d70d\/Headshot.png)\n\nWritten by:\n\n[Katherine Krive, DO](https:\/\/www.goodrx.com\/about\/bio\/katherine-krive)\n\nKatherine Krive, DO, is a freelance medical writer and editor. She is also a psychiatrist who has practiced in hospital, academic, and community settings.\n\n![Katie E. Golden, MD](https:\/\/images.ctfassets.net\/4f3rgqwzdznj\/491qgaKVwSdYx6oA4WaGQw\/fba8bf9652d561990e7b612874ad74d6\/katie_golden_goodrx.webp)\n\n![Katie E. Golden, MD](https:\/\/images.ctfassets.net\/4f3rgqwzdznj\/491qgaKVwSdYx6oA4WaGQw\/fba8bf9652d561990e7b612874ad74d6\/katie_golden_goodrx.webp)\n\nEdited by:\n\n[Katie E. Golden, MD](https:\/\/www.goodrx.com\/about\/bio\/katie-golden)\n\nKatie E. Golden, MD, is a board-certified emergency medicine physician and a medical editor at GoodRx.\n\n![Joshua Murdock, PharmD, BCBBS](https:\/\/images.ctfassets.net\/4f3rgqwzdznj\/6rpjpT3B1dTVGDH0Ws2UMg\/6308582b6d1a82376657002d7a3b6ae2\/joshua_murdock_goodrx.webp)\n\n![Joshua Murdock, PharmD, BCBBS](https:\/\/images.ctfassets.net\/4f3rgqwzdznj\/6rpjpT3B1dTVGDH0Ws2UMg\/6308582b6d1a82376657002d7a3b6ae2\/joshua_murdock_goodrx.webp)\n\nReviewed by:\n\n[Joshua Murdock, PharmD, BCBBS](https:\/\/www.goodrx.com\/about\/bio\/joshua-murdock)\n\nJoshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.\n\n![Green trust check mark](https:\/\/www.grxstatic.com\/images\/green-check-mark.svg)[Our editorial standards](https:\/\/www.goodrx.com\/about\/editorial-guidelines)\n\n![Green trust check mark](https:\/\/www.grxstatic.com\/images\/green-check-mark.svg)[Meet our experts](https:\/\/www.goodrx.com\/about\/health#meet-our-healthcare-experts)\n\n## References\nde Sousa, R. T., et al. (2015). [Challenging treatment-resistant major depressive disorder: A roadmap for improved therapeutics](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4761633\/). *Current Neuropharmacology*.\n\nGaynes, B. N., et al. (2020). [Defining treatment-resistant depression](https:\/\/pubmed.ncbi.nlm.nih.gov\/31638723\/). *Depression and Anxiety*.\n\n### View All References (7)\nGelenberg, A. J., et al. (2010). [Practice guidelines for the treatment of patients with major depressive disorder](https:\/\/psychiatryonline.org\/pb\/assets\/raw\/sitewide\/practice_guidelines\/guidelines\/mdd-1410197717630.pdf). American Psychiatric Association.\n\nGutierrez, G., et al. (2024). [IV low dose ketamine infusions for treatment resistant depression: Results from a five-year study at a free public clinic in an academic hospital](https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0165178124001501). *Psychiatry Research*.\n\nKuczynski, A. M., et al. (2021). [The effect of social interaction quantity and quality on depressed mood and loneliness: A daily diary study](https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/02654075211045717). *Journal of Social and Personal Relationships*.\n\nMura, G., et al. (2014). [Exercise as an add-on strategy for the treatment of major depressive disorder: A systematic review](https:\/\/www.cambridge.org\/core\/journals\/cns-spectrums\/article\/abs\/exercise-as-an-addon-strategy-for-the-treatment-of-major-depressive-disorder-a-systematic-review\/879856D988F804EE03393226324BA176). *CNS Spectrums*.\n\nNuñez, N. A., et al. (2022). [Augmentation strategies for treatment resistant major depression: A systematic review and network meta-analysis](https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0165032721014518?via%3Dihub). *Journal of Affective Disorders*.\n\nPsychology Today. (n.d.). [Transcranial magnetic stimulation therapy](https:\/\/www.psychologytoday.com\/us\/basics\/transcranial-magnetic-stimulation-therapy).\n\nVoineskos, D., et al. (2020). [Management of treatment-resistant depression: Challenges and strategies](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6982454\/). *Neuropsychiatric Disease and Treatment*.\n\nGoodRx Health has strict sourcing policies and relies on primary sources such as medical organizations, governmental agencies, academic institutions, and peer-reviewed scientific journals. Learn more about how we ensure our content is accurate, thorough, and unbiased by reading our [editorial guidelines](https:\/\/www.goodrx.com\/about\/editorial-guidelines).\n\nde Sousa, R. T., et al. (2015). [Challenging treatment-resistant major depressive disorder: A roadmap for improved therapeutics](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4761633\/). *Current Neuropharmacology*.\n\nGaynes, B. N., et al. (2020). [Defining treatment-resistant depression](https:\/\/pubmed.ncbi.nlm.nih.gov\/31638723\/). *Depression and Anxiety*.\n\nGelenberg, A. J., et al. (2010). [Practice guidelines for the treatment of patients with major depressive disorder](https:\/\/psychiatryonline.org\/pb\/assets\/raw\/sitewide\/practice_guidelines\/guidelines\/mdd-1410197717630.pdf). American Psychiatric Association.\n\nGutierrez, G., et al. (2024). [IV low dose ketamine infusions for treatment resistant depression: Results from a five-year study at a free public clinic in an academic hospital](https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0165178124001501). *Psychiatry Research*.\n\nKuczynski, A. M., et al. (2021). [The effect of social interaction quantity and quality on depressed mood and loneliness: A daily diary study](https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/02654075211045717). *Journal of Social and Personal Relationships*.\n\nMura, G., et al. (2014). [Exercise as an add-on strategy for the treatment of major depressive disorder: A systematic review](https:\/\/www.cambridge.org\/core\/journals\/cns-spectrums\/article\/abs\/exercise-as-an-addon-strategy-for-the-treatment-of-major-depressive-disorder-a-systematic-review\/879856D988F804EE03393226324BA176). *CNS Spectrums*.\n\nNuñez, N. A., et al. (2022). [Augmentation strategies for treatment resistant major depression: A systematic review and network meta-analysis](https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0165032721014518?via%3Dihub). *Journal of Affective Disorders*.\n\nPsychology Today. (n.d.). [Transcranial magnetic stimulation therapy](https:\/\/www.psychologytoday.com\/us\/basics\/transcranial-magnetic-stimulation-therapy).\n\nVoineskos, D., et al. (2020). [Management of treatment-resistant depression: Challenges and strategies](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6982454\/). *Neuropsychiatric Disease and Treatment*.\n##### *For additional resources or to connect with mental health services in your area, call SAMHSA’s National Helpline at* [*1-800-662-4357*](tel:1-800-662-4357)*. For immediate assistance, call the* [*National Suicide Prevention Lifeline*](https:\/\/988lifeline.org\/) *at* [*988*](tel:988)*, or text HOME to* [*741-741*](<sms: 741-741>) *to reach the* [*Crisis Text Line*](https:\/\/www.crisistextline.org\/)*.*\n\n![Newsletter Subscription](https:\/\/www.grxstatic.com\/images\/notification-email-female.svg)\n\n#### Subscribe and save\nGet prescription saving tips and more from GoodRx Health. 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What You Need to Know If You Take SSRIs Written by Sameer Hassamal, MDUpdated on Feb 26, 2026 by Sameer Hassamal, MD • Feb 26, 2026](https:\/\/www.goodrx.com\/classes\/ssris\/what-is-serotonin-syndrome)\n\n[![psychedelics: closeup LSD pills 1267303677](https:\/\/www.grxstatic.com\/4f3rgqwzdznj\/1xqwUlpmpMrGrjls6Nl9zs\/87f96179e02c49f6f76199071a788eea\/closeup_LSD_pills_1267303677.webp?w=640&q=85&fm=webp) Psychedelics Psychedelics Legalization Pipeline: 4 Psychedelic Drugs Seeking FDA Approval Written by Stacia Woodcock, PharmDPublished on Feb 25, 2026 by Stacia Woodcock, PharmD • Feb 25, 2026](https:\/\/www.goodrx.com\/health-topic\/psychedelics\/psychedelics-legalization)\n\n[![middle aged woman looking out window 1047378038](https:\/\/www.grxstatic.com\/4f3rgqwzdznj\/4BEoN8cwZGFjbzRnPPPcVx\/1a4776e2c9d30c7c88f988b144c1f457\/middle_aged_woman_looking_out_window_1047378038.webp?w=640&q=85&fm=webp) Menopause The Links Between Menopause and Depression Written by Christina Palmer, MDUpdated on Feb 13, 2026 by Christina Palmer, MD • Feb 13, 2026](https:\/\/www.goodrx.com\/conditions\/menopause\/menopause-and-depression)\n\n[![How to Know Your Depression Medication Isn’t Working for You](https:\/\/content.jwplatform.com\/thumbs\/kGH95KZC-720.jpg?width=640&quality=85&auto=webp) ![Video play button](https:\/\/www.grxstatic.com\/images\/play-dark.svg) Depression Signs Your Antidepressant Is Working: Wellbutrin, Effexor, Prozac, and More 2:35 2:35](https:\/\/www.goodrx.com\/conditions\/depression\/signs-your-antidepressant-is-working)\n\n[![caplyta: senior woman with worried expression 1601471196](https:\/\/www.grxstatic.com\/4f3rgqwzdznj\/76WWpAAOfJENCEEua6LqYR\/35d1b27951d893e5209fcf2b08e31f98\/senior_woman_with_worried_expression_1601471196.jpg?w=640&q=85&fm=webp) Caplyta How Long Does It Take for Caplyta to Work? 5 Answers to Caplyta FAQs Written by Sarah Morin, RPhUpdated on Feb 11, 2026 by Sarah Morin, RPh • Feb 11, 2026](https:\/\/www.goodrx.com\/caplyta\/caplyta-faqs)\n\n[![Men's Health: man taking medication at home 1960400023](https:\/\/www.grxstatic.com\/4f3rgqwzdznj\/BNjZ30r3nBj6jzup31wz3\/d0a0b27b93c5b988d6b6b0b5e6dbdbe6\/man_taking_medication_at_home_1960400023.webp?w=640&q=85&fm=webp) Men's Health Drugs for Men: A GoodRx Savings Guide to 7 Notable Men’s Health Medications Written by Joshua Murdock, PharmD, BCBBSUpdated on Feb 2, 2026 by Joshua Murdock, PharmD, BCBBS • Feb 2, 2026](https:\/\/www.goodrx.com\/health-topic\/mens-health\/common-medications-for-men)\n\n[![Ozempic: sad man looking through window 606671220](https:\/\/www.grxstatic.com\/4f3rgqwzdznj\/7AdVkfEG0tEKXepUybP9Cm\/455c5199f90bd16a7d3cec561381add2\/sad_man_looking_through_window_606671220.jpg?w=640&q=85&fm=webp) Ozempic Can Ozempic Cause Depression or Suicidal Thoughts? Written by Frank Schwalbe, MDUpdated on Jan 27, 2026 by Frank Schwalbe, MD • Jan 27, 2026](https:\/\/www.goodrx.com\/ozempic\/depression-suicidal-side-effects)\n\n[![Spravato: pharmacy tips spravato 2](https:\/\/www.grxstatic.com\/4f3rgqwzdznj\/1A5ZlBVXTn2P350FpLDJHB\/71a3940c3dd2198c5198c922abe5d2eb\/pharmacy_tips_spravato_2.png?w=640&q=85&fm=webp) Spravato What To Do Before And After Spravato Treatment: 8 Tips for Using Spravato Safely Written by Jill Barat, PharmDUpdated on Dec 18, 2025 by Jill Barat, PharmD • Dec 18, 2025](https:\/\/www.goodrx.com\/spravato\/how-to-get-the-most-from-spravato)\n\n[![depression: woman crying 1464880114](https:\/\/www.grxstatic.com\/4f3rgqwzdznj\/5Bx5eBtbk6T8WmJLOnFJJ7\/19d78b8243230decbbea2b0e26a391d0\/woman_crying_1464880114.webp?w=640&q=85&fm=webp) Depression The 8 Best Supplements for Depression Written by Nicole Andonian, MDPublished on Dec 10, 2025 by Nicole Andonian, MD • Dec 10, 2025](https:\/\/www.goodrx.com\/conditions\/depression\/natural-remedies-for-depression)\n\n[![Depression: Post-partum medications: carrying baby looking outside 1314524633](https:\/\/www.grxstatic.com\/4f3rgqwzdznj\/28m1zMHIZcQ6ezUeWeP6hI\/37463fcd344b7688fc9c2b7dc7017b96\/carrying_baby_looking_outside-1314524633.webp?w=640&q=85&fm=webp) Postpartum Depression Which Medications Work Best to Treat Postpartum Depression? Written by Sarah Gupta, MDUpdated on Nov 20, 2025 by Sarah Gupta, MD • Nov 20, 2025](https:\/\/www.goodrx.com\/conditions\/postpartum-depression\/best-postpartum-depression-meds)\n\n[![caplyta: caplyta dosage](https:\/\/www.grxstatic.com\/4f3rgqwzdznj\/2jRevK4TZRu4dgU2XJIgvT\/fea9e5180ef33d30a37354d341967902\/caplyta_dosage.png?w=640&q=85&fm=webp) Caplyta Caplyta Dosages for Adults: Your GoodRx Guide Written by Sarah Morin, RPhUpdated on Nov 10, 2025 by Sarah Morin, RPh • Nov 10, 2025](https:\/\/www.goodrx.com\/caplyta\/dosage)\n\n[![bupoprion: HCP speaking to a patient 2223908328](https:\/\/www.grxstatic.com\/4f3rgqwzdznj\/7ycsQOpf8gJSamLJnCCpVz\/a14940280bb768846608e4d8584bb048\/HCP_speaking_to_a_patient_2223908328.webp?w=640&q=85&fm=webp) Bupropion Want to Stop Taking Wellbutrin? 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If you are having difficulty accessing this website, please call or email us at [1-855-268-2822](<tel: +18552682822>) or [ada@goodrx.com](<mailto: ada@goodrx.com>) so that we can provide you with the services you require through alternative means.\n\nCopyright ©2011–2026 GoodRx, Inc.\n\n[![LegitScript Logo, opens in a new window](https:\/\/static.legitscript.com\/seals\/338276.png?width=256&quality=85&auto=webp)](https:\/\/www.legitscript.com\/websites\/?checker_keywords=goodrx.com)[![National Association of Boards of Pharmacy Logo, opens in a new window](https:\/\/www.grxstatic.com\/4f3rgqwzdznj\/7BflV93nkrARWlhjT0OpL3\/41f2d7661bc44e0b14eac2269c92bd0b\/6e174cd343d6b3b47288ee3ea13a61ab.png?format=png&auto=webp&width=182?w=384&q=85&fm=webp)](https:\/\/safe.pharmacy\/buy-safely\/)[![Better Business Bureau Logo, opens in a new window](https:\/\/www.grxstatic.com\/4f3rgqwzdznj\/xXC4tWf17QuV268j1yOiR\/4d2427d015a8d78f83af07b8c9a9ba3f\/2dea00a13eeceedf6c458d97e3bc9163.png?format=png&auto=webp&width=121?w=256&q=85&fm=webp)](https:\/\/www.bbb.org\/us\/ca\/santa-monica\/profile\/online-pharmacy\/goodrx-1216-351397#bbbseal)\n\n![](https:\/\/sb.scorecardresearch.com\/p?c1=2&c2=33256513&cs_ucfr=1)\n\n![](https:\/\/match.prod.bidr.io\/cookie-sync\/goodrx?buyer_user_id=undefined&env=prod)\n\n![](https:\/\/cnv.event.prod.bidr.io\/log\/cnv?tag_id=6&buzz_key=goodrx&value=1&segment_key=&account_id=4&ord=1995232940)\n\n![](https:\/\/sync.graph.bluecava.com\/p.png?p=ddb38364-ed0e-11ec-8ee0-4201ac10000b&segment=732bbede0eedec11834342010a78800a&uid=undefined&event=page_view&rn=1775361119209)","attrs_readable_markdown":"## Key takeaways:\n- If you still feel depressed after trying antidepressants, you may have something called treatment-resistant depression.\n- Though the name may sound discouraging, treatment-resistant depression is treatable.\n- There are many therapies that can help with treatment-resistant depression. These include medications and nonmedication options.\n\nHave you been told that you have treatment-resistant depression? This is a term used by some healthcare professionals that can be confusing and disheartening. You may think it means that you have depression that won’t get any better. But that’s not the case at all. It just means it’s time to try something else. And you actually have many different treatment options that can help this kind of depression.\n\nTreatment-resistant depression refers to symptoms of depression that are ongoing even with treatment. These treatments are usually antidepressant medications.\n\nBut the term “treatment-resistant depression” isn’t very useful for people with depression or even for healthcare professionals. That’s because experts don’t agree on the exact [definition](https:\/\/pubmed.ncbi.nlm.nih.gov\/31638723\/). Some say it’s depression that persists after a period of taking just one medication. Others say it should be diagnosed after two or three failed medication trials.\n\nAlso, people can feel like the term means that their depression will never get better. They may start to lose hope after trying medications that weren’t too helpful for them. In reality, [many people](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4761633\/) don’t feel much better after their first or second antidepressant.\n\nDepression can be hard to treat, for many reasons:\n\n- Everyone has a unique brain that doesn’t react the same way to medication. Certain medications can be really helpful for one person and not for another, and no one knows why.\n- Medication can cause side effects that can make a person feel bad, like [weight gain](https:\/\/www.goodrx.com\/conditions\/depression\/antidepressants-weight-gain) or [sexual side effects](https:\/\/www.goodrx.com\/drugs\/side-effects\/these-drugs-may-be-affecting-your-sex-life#antidepressants). These can happen even if the medication is helping the original depression. So this can make it hard to know if the medication is helping.\n- There are many factors in life that affect people’s moods. Medication doesn’t address social problems or lifestyle factors that can worsen depression.\n\nBut treatment-resistant depression can improve with ongoing treatment. Theresa Toledo, MD, is a psychiatrist in southeast Michigan who works with mood disorders including depression. She said that “treatment-resistant does not imply that depression cannot get better.”\n\nYou and your healthcare team may want to look at different options for treatment. This can start with a change in medications.\n\n- Nearly every day\n- More than half the days\n- Several days\n- Not at all\n\n### In the past 2 weeks, have you felt down, depressed, or hopeless:\n- Nearly every day\n- More than half the days\n- Several days\n- Not at all\n\n### In the past 2 weeks, have you had trouble falling asleep, staying asleep, or sleeping too much:\n- Nearly every day\n- More than half the days\n- Several days\n- Not at all\n\n### In the past 2 weeks, have you felt tired or had little energy:\n- Nearly every day\n- More than half the days\n- Several days\n- Not at all\n\n### In the past 2 weeks, have you had a poor appetite or overeaten:\n- Nearly every day\n- More than half the days\n- Several days\n- Not at all\n\n### In the past 2 weeks, have you felt bad about yourself — or that you’re a failure, or have let yourself or your family down:\n- Nearly every day\n- More than half the days\n- Several days\n- Not at all\n\n### In the past 2 weeks, have you had trouble concentrating on things, like reading or watching television:\n- Nearly every day\n- More than half the days\n- Several days\n- Not at all\n\n### In the past 2 weeks, have you either been so slowed down or so restless that other people could have noticed:\n- Nearly every day\n- More than half the days\n- Several days\n- Not at all\n\n### In the past 2 weeks, have you had thoughts about hurting yourself in some way, or that you would be better off dead:\n- Nearly every day\n- More than half the days\n- Several days\n- Not at all\n\nSeveral kinds of medications can be useful for treatment-resistant depression. Switching to a different antidepressant can be helpful. And other types of medications can enhance the effects of an antidepressant. It’s common to use a combination of medications for treatment-resistant depression.\n\nThe most common medications used for depression are [selective serotonin reuptake inhibitors](https:\/\/www.goodrx.com\/classes\/ssris\/ssri-list) (SSRIs). And even though they are called antidepressants, SSRIs are also prescribed for anxiety. There are several different SSRIs, and one of them may work better for you than another.\n\nCommon SSRIs include:\n\nCompare prices and information on the most popular Depression medications.\n\n[Serotonin and norepinephrine reuptake inhibitors](https:\/\/www.goodrx.com\/classes\/snris\/snri-drugs-list) (SNRIs) are another kind of antidepressant. Like SSRIs, SNRIs affect [serotonin](https:\/\/www.goodrx.com\/health-topic\/hormones\/serotonin) in the brain, which helps to regulate mood. But they also affect [norepinephrine](https:\/\/www.goodrx.com\/classes\/snris\/snri-side-effects). Because of this, SNRIs can be helpful for chronic pain and anxiety, too.\n\nCommon SNRIs include:\n\nThere are other kinds of antidepressants that work on slightly different brain chemicals:\n\n- [Vortioxetine](https:\/\/www.goodrx.com\/trintellix\/what-is) (Trintellix) and [vilazodone](https:\/\/www.goodrx.com\/viibryd\/what-is) (Viibryd) are similar to SSRIs. But they also affect different serotonin brain receptors.\n- [Mirtazapine](https:\/\/www.goodrx.com\/mirtazapine\/what-is) (Remeron) is an antidepressant that also affects histamine. This can be helpful for sleep.\n- [Bupropion](https:\/\/www.goodrx.com\/bupropion\/what-is) (Wellbutrin SR, Wellbutrin XL) affects norepinephrine and dopamine. It can sometimes double as a [treatment for ADHD](https:\/\/www.goodrx.com\/wellbutrin\/how-it-works) (attention-deficit hyperactivity disorder).\n- [Auvelity](https:\/\/www.goodrx.com\/auvelity\/what-is) is a newer antidepressant that’s a combination of two medications — dextromethorphan and bupropion. Dextromethorphan affects a specific receptor in the brain called the NMDA receptor.\n\nAdding [antipsychotic medications](https:\/\/www.goodrx.com\/health-topic\/mental-health\/typical-vs-atypical-antipsychotics) to antidepressants can also be helpful for treatment-resistant depression. These are usually used to treat conditions such as [bipolar disorder](https:\/\/www.goodrx.com\/conditions\/bipolar-disorder) and [schizophrenia](https:\/\/www.goodrx.com\/conditions\/schizophrenia). But [lower doses](https:\/\/psychiatryonline.org\/pb\/assets\/raw\/sitewide\/practice_guidelines\/guidelines\/mdd-1410197717630.pdf) of these medications can be helpful in depression.\n\nThe FDA has approved these antipsychotics as medications for depression:\n\n- [Aripiprazole](https:\/\/www.goodrx.com\/aripiprazole\/what-is) (Abilify)\n- [Brexpiprazole](https:\/\/www.goodrx.com\/rexulti\/what-is) (Rexulti)\n- [Cariprazine](https:\/\/www.goodrx.com\/vraylar\/what-is) (Vraylar)\n- [Olanzapine](https:\/\/www.goodrx.com\/olanzapine\/what-is) (Zyprexa)\n- [Quetiapine](https:\/\/www.goodrx.com\/quetiapine\/what-is) (Seroquel)\n- [Symbyax](https:\/\/www.goodrx.com\/symbyax\/what-is) (Olanzapine\/fluoxetine)\n\nThere are other [kinds of medications](https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0165032721014518?via%3Dihub) — beyond antidepressants and antipsychotics — that have also been shown to be helpful for treatment-resistant depression.\n\n[Spravato](https:\/\/www.goodrx.com\/spravato\/what-is) (esketamine) is a newer medication that’s FDA approved for treatment-resistant depression. It’s a form of ketamine, which is an IV medication that’s sometimes used as a [type of anesthesia](https:\/\/www.goodrx.com\/conditions\/anesthesia\/types-of-anesthesia). The IV form of ketamine is also used for [off-label treatment](https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0165178124001501) for treatment-resistant depression. But Spravato is a nasal spray that you can receive in a healthcare office. This is so your healthcare team can watch for potential side effects for a couple of hours after each dose.\n\nThere are other medications that are sometimes used in addition to more common depression treatments. But it’s important to note that they aren’t officially FDA approved for depression. Because of this, they are only used in specific circumstances and with the guidance of an experienced healthcare professional:\n\n- [Lithium](https:\/\/www.goodrx.com\/lithium\/what-is) is usually used for stabilizing mood in bipolar disorder. It can improve mood in treatment-resistant depression, too. But blood levels need to be checked during treatment to prevent possible [lithium toxicity](https:\/\/www.goodrx.com\/lithium\/what-lithium-side-effects-should-you-expect#lithium-toxicity).\n- [Thyroid hormone](https:\/\/www.goodrx.com\/synthroid\/what-is) ([levothyroxine](https:\/\/www.goodrx.com\/synthroid\/what-is)) can also be added to antidepressants. Your prescriber will want to track your thyroid function while you’re taking this hormone.\n- Llisdexamfetamine ([Vyvanse](https:\/\/www.goodrx.com\/vyvanse\/what-is)) is a stimulant medication usually used for ADHD. It has also been shown to be helpful as an add-on for depression.\n- [Buspirone](https:\/\/www.goodrx.com\/buspirone\/what-is) (Buspar) is a medication that can sometimes be used to treat anxiety.\n\nTreatments other than medications have proved helpful for treatment-resistant depression.\n\nStudies show that [psychotherapy](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6982454\/) is helpful for treatment-resistant depression. The most helpful kinds of therapy for treatment-resistant depression are:\n\n- **Cognitive behavioral therapy (CBT):** This well-known therapy helps you understand how you think, behave, and feel. [CBT](https:\/\/www.goodrx.com\/health-topic\/mental-health\/cognitive-behavioral-therapy) helps you recognize and make changes to thinking patterns that contribute to depression.\n- **Interpersonal therapy:** This kind of therapy focuses on making relationships better.\n- **Mindfulness-based cognitive therapy:** Learning how to be present in the moment is a helpful way to understand and ease symptoms of depression and anxiety.\n\nTalking to a therapist is often an important part of treating depression. Therapy can help you change your mindset and the ways you go about your life. It can help you think about things differently. You may have tried therapy and felt it was not helpful. But try not to get discouraged. It may just mean you need to keep looking until you [find a therapist](https:\/\/www.goodrx.com\/health-topic\/mental-health\/psychiatrist-vs-psychologist) who is the right fit for you.\n\n[Electroconvulsive therapy](https:\/\/www.goodrx.com\/conditions\/depression\/depression-ect) (ECT) is a depression treatment that uses controlled seizures. This may sound scary, but it can actually be quite effective. In fact, ECT has been named the “gold standard” for treating treatment-resistant depression.\n\nFirst, the person receives anesthetic medication so that they are relaxed and not aware of the seizure. Then a healthcare professional uses an electrical charge to the scalp to start a brief seizure. Since the person is asleep, this isn’t painful. The treatment is repeated over a period of several weeks or months. It’s an outpatient procedure and considered to be safer than surgery.\n\n[Transcranial magnetic stimulation](https:\/\/www.psychologytoday.com\/us\/basics\/transcranial-magnetic-stimulation-therapy) (TMS) is another procedure that can help treatment-resistant depression. A magnetic coil is placed on the scalp in a medical office. An electrical current is passed through a part of the brain. Like ECT, this is not painful. This procedure is also repeated over the course of several weeks.\n\nVagal nerve stimulation (VNS) uses an electrical stimulator in the body to activate the vagus nerve. The vagus nerve is a large nerve in the body that’s important in the parasympathetic nervous system. This is the part of the nervous system that helps the body rest and relax.\n\nThis treatment requires a small procedure. A surgeon implants the stimulator in the neck, where the nerve is located. It treats both treatment-resistant depression and epilepsy.\n\nDepression has a way of making people neglect themselves. When you take time to do things you used to enjoy, even if you don’t want to at the moment, it can help your mood. Also, taking care of yourself is part of the bigger picture in your depression treatment.\n\n“I always emphasize there are three important things we do for mental health treatment,” Toledo said. Those are:\n\n- Medication\n- Psychotherapy\n- Overall health and habits, including sleep, diet, and exercise\n\nStudies show that [exercise](https:\/\/www.cambridge.org\/core\/journals\/cns-spectrums\/article\/abs\/exercise-as-an-addon-strategy-for-the-treatment-of-major-depressive-disorder-a-systematic-review\/879856D988F804EE03393226324BA176) can be helpful for treatment-resistant depression. Many people with depression have a [hard time getting motivated to exercise](https:\/\/www.goodrx.com\/well-being\/movement-exercise\/working-out-tired). But research shows that exercise helps people with depression who are already taking an antidepressant. And every little bit helps. This can be as simple as moving and stretching your body more in your daily routines.\n\nDepression can feel worse when you feel physically down, too. Changing your diet and drinking enough water may help you feel better. Foods with fiber, protein, and complex carbohydrates will help to maintain your metabolism.\n\nResearch on the [gut-brain connection](https:\/\/www.goodrx.com\/health-topic\/mental-health\/brain-gut-connection) is becoming more common. This term describes how the nerves of the stomach and intestines are related to the brain. Keeping the gut healthy could help your mental health.\n\nPeople with depression are more likely to isolate themselves from others and experience loneliness. But research shows that increased [social interaction](https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/02654075211045717) can help with mood and loneliness. It may be difficult to be social, but spending time with loved ones — or even people you don’t know very well — can help lift you up.\n\nLook at your relationships to see if you are stuck in an unhealthy rut. Sometimes, people don’t realize how much their relationships affect their mood. These unhealthy relationships can be with partners, family, friends, or colleagues. Therapy is a good setting to work through your feelings about relationships.\n\nDon’t neglect your physical health when focused on treating your depression. Toledo also noted that it’s important to get a checkup with your primary care provider. “Maintaining overall health is important,” she said. “Your primary care provider can rule out conditions that can make depression worse. Examples are anemia, diabetes, and thyroid disease.”\n\n## The bottom line\nTreatment-resistant depression doesn’t mean that your depression is untreatable. Trying different medications or combinations is an option. Depression can improve with therapy, exercise, and other lifestyle strategies. If you’ve heard the term “treatment resistant” describe your depression, don’t give up hope on feeling better. Many times, it’s just a matter of finding the right treatment formula that works best for you.\n\n![why trust our exports reliability shield](https:\/\/www.grxstatic.com\/images\/reliability.svg)\n\n![Katherine Krive, DO](https:\/\/images.ctfassets.net\/4f3rgqwzdznj\/1dm4QxniN8Pv1FV29c1G3Z\/63b503548e50e254d09785aed218d70d\/Headshot.png)\n\n![Katherine Krive, DO](https:\/\/images.ctfassets.net\/4f3rgqwzdznj\/1dm4QxniN8Pv1FV29c1G3Z\/63b503548e50e254d09785aed218d70d\/Headshot.png)\n\nKatherine Krive, DO, is a freelance medical writer and editor. She is also a psychiatrist who has practiced in hospital, academic, and community settings.\n\n![Katie E. Golden, MD](https:\/\/images.ctfassets.net\/4f3rgqwzdznj\/491qgaKVwSdYx6oA4WaGQw\/fba8bf9652d561990e7b612874ad74d6\/katie_golden_goodrx.webp)\n\n![Katie E. Golden, MD](https:\/\/images.ctfassets.net\/4f3rgqwzdznj\/491qgaKVwSdYx6oA4WaGQw\/fba8bf9652d561990e7b612874ad74d6\/katie_golden_goodrx.webp)\n\nKatie E. Golden, MD, is a board-certified emergency medicine physician and a medical editor at GoodRx.\n\n![Joshua Murdock, PharmD, BCBBS](https:\/\/images.ctfassets.net\/4f3rgqwzdznj\/6rpjpT3B1dTVGDH0Ws2UMg\/6308582b6d1a82376657002d7a3b6ae2\/joshua_murdock_goodrx.webp)\n\n![Joshua Murdock, PharmD, BCBBS](https:\/\/images.ctfassets.net\/4f3rgqwzdznj\/6rpjpT3B1dTVGDH0Ws2UMg\/6308582b6d1a82376657002d7a3b6ae2\/joshua_murdock_goodrx.webp)\n\nJoshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.\n\nGoodRx Health has strict sourcing policies and relies on primary sources such as medical organizations, governmental agencies, academic institutions, and peer-reviewed scientific journals. Learn more about how we ensure our content is accurate, thorough, and unbiased by reading our [editorial guidelines](https:\/\/www.goodrx.com\/about\/editorial-guidelines).","meta_canonical":null}

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Meta Title	Treatment-Resistant Depression: Treatment Options to Know - GoodRx
Meta Description	An antidepressant isn’t always enough to ease the symptoms of depression. If you have treatment-resistant depression, there are many treatment options out there.
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Boilerpipe Text	Key takeaways: If you still feel depressed after trying antidepressants, you may have something called treatment-resistant depression. Though the name may sound discouraging, treatment-resistant depression is treatable. There are many therapies that can help with treatment-resistant depression. These include medications and nonmedication options. Have you been told that you have treatment-resistant depression? This is a term used by some healthcare professionals that can be confusing and disheartening. You may think it means that you have depression that won’t get any better. But that’s not the case at all. It just means it’s time to try something else. And you actually have many different treatment options that can help this kind of depression. Treatment-resistant depression refers to symptoms of depression that are ongoing even with treatment. These treatments are usually antidepressant medications. But the term “treatment-resistant depression” isn’t very useful for people with depression or even for healthcare professionals. That’s because experts don’t agree on the exact definition . Some say it’s depression that persists after a period of taking just one medication. Others say it should be diagnosed after two or three failed medication trials. Also, people can feel like the term means that their depression will never get better. They may start to lose hope after trying medications that weren’t too helpful for them. In reality, many people don’t feel much better after their first or second antidepressant. Depression can be hard to treat, for many reasons: Everyone has a unique brain that doesn’t react the same way to medication. Certain medications can be really helpful for one person and not for another, and no one knows why. Medication can cause side effects that can make a person feel bad, like weight gain or sexual side effects . These can happen even if the medication is helping the original depression. So this can make it hard to know if the medication is helping. There are many factors in life that affect people’s moods. Medication doesn’t address social problems or lifestyle factors that can worsen depression. But treatment-resistant depression can improve with ongoing treatment. Theresa Toledo, MD, is a psychiatrist in southeast Michigan who works with mood disorders including depression. She said that “treatment-resistant does not imply that depression cannot get better.” You and your healthcare team may want to look at different options for treatment. This can start with a change in medications. Nearly every day More than half the days Several days Not at all In the past 2 weeks, have you felt down, depressed, or hopeless: Nearly every day More than half the days Several days Not at all In the past 2 weeks, have you had trouble falling asleep, staying asleep, or sleeping too much: Nearly every day More than half the days Several days Not at all In the past 2 weeks, have you felt tired or had little energy: Nearly every day More than half the days Several days Not at all In the past 2 weeks, have you had a poor appetite or overeaten: Nearly every day More than half the days Several days Not at all In the past 2 weeks, have you felt bad about yourself — or that you’re a failure, or have let yourself or your family down: Nearly every day More than half the days Several days Not at all In the past 2 weeks, have you had trouble concentrating on things, like reading or watching television: Nearly every day More than half the days Several days Not at all In the past 2 weeks, have you either been so slowed down or so restless that other people could have noticed: Nearly every day More than half the days Several days Not at all In the past 2 weeks, have you had thoughts about hurting yourself in some way, or that you would be better off dead: Nearly every day More than half the days Several days Not at all Several kinds of medications can be useful for treatment-resistant depression. Switching to a different antidepressant can be helpful. And other types of medications can enhance the effects of an antidepressant. It’s common to use a combination of medications for treatment-resistant depression. The most common medications used for depression are selective serotonin reuptake inhibitors (SSRIs). And even though they are called antidepressants, SSRIs are also prescribed for anxiety. There are several different SSRIs, and one of them may work better for you than another. Common SSRIs include: Compare prices and information on the most popular Depression medications. Serotonin and norepinephrine reuptake inhibitors (SNRIs) are another kind of antidepressant. Like SSRIs, SNRIs affect serotonin in the brain, which helps to regulate mood. But they also affect norepinephrine . Because of this, SNRIs can be helpful for chronic pain and anxiety, too. Common SNRIs include: There are other kinds of antidepressants that work on slightly different brain chemicals: Vortioxetine (Trintellix) and vilazodone (Viibryd) are similar to SSRIs. But they also affect different serotonin brain receptors. Mirtazapine (Remeron) is an antidepressant that also affects histamine. This can be helpful for sleep. Bupropion (Wellbutrin SR, Wellbutrin XL) affects norepinephrine and dopamine. It can sometimes double as a treatment for ADHD (attention-deficit hyperactivity disorder). Auvelity is a newer antidepressant that’s a combination of two medications — dextromethorphan and bupropion. Dextromethorphan affects a specific receptor in the brain called the NMDA receptor. Adding antipsychotic medications to antidepressants can also be helpful for treatment-resistant depression. These are usually used to treat conditions such as bipolar disorder and schizophrenia . But lower doses of these medications can be helpful in depression. The FDA has approved these antipsychotics as medications for depression: Aripiprazole (Abilify) Brexpiprazole (Rexulti) Cariprazine (Vraylar) Olanzapine (Zyprexa) Quetiapine (Seroquel) Symbyax (Olanzapine/fluoxetine) There are other kinds of medications — beyond antidepressants and antipsychotics — that have also been shown to be helpful for treatment-resistant depression. Spravato (esketamine) is a newer medication that’s FDA approved for treatment-resistant depression. It’s a form of ketamine, which is an IV medication that’s sometimes used as a type of anesthesia . The IV form of ketamine is also used for off-label treatment for treatment-resistant depression. But Spravato is a nasal spray that you can receive in a healthcare office. This is so your healthcare team can watch for potential side effects for a couple of hours after each dose. There are other medications that are sometimes used in addition to more common depression treatments. But it’s important to note that they aren’t officially FDA approved for depression. Because of this, they are only used in specific circumstances and with the guidance of an experienced healthcare professional: Lithium is usually used for stabilizing mood in bipolar disorder. It can improve mood in treatment-resistant depression, too. But blood levels need to be checked during treatment to prevent possible lithium toxicity . Thyroid hormone ( levothyroxine ) can also be added to antidepressants. Your prescriber will want to track your thyroid function while you’re taking this hormone. Llisdexamfetamine ( Vyvanse ) is a stimulant medication usually used for ADHD. It has also been shown to be helpful as an add-on for depression. Buspirone (Buspar) is a medication that can sometimes be used to treat anxiety. Treatments other than medications have proved helpful for treatment-resistant depression. Studies show that psychotherapy is helpful for treatment-resistant depression. The most helpful kinds of therapy for treatment-resistant depression are: Cognitive behavioral therapy (CBT): This well-known therapy helps you understand how you think, behave, and feel. CBT helps you recognize and make changes to thinking patterns that contribute to depression. Interpersonal therapy: This kind of therapy focuses on making relationships better. Mindfulness-based cognitive therapy: Learning how to be present in the moment is a helpful way to understand and ease symptoms of depression and anxiety. Talking to a therapist is often an important part of treating depression. Therapy can help you change your mindset and the ways you go about your life. It can help you think about things differently. You may have tried therapy and felt it was not helpful. But try not to get discouraged. It may just mean you need to keep looking until you find a therapist who is the right fit for you. Electroconvulsive therapy (ECT) is a depression treatment that uses controlled seizures. This may sound scary, but it can actually be quite effective. In fact, ECT has been named the “gold standard” for treating treatment-resistant depression. First, the person receives anesthetic medication so that they are relaxed and not aware of the seizure. Then a healthcare professional uses an electrical charge to the scalp to start a brief seizure. Since the person is asleep, this isn’t painful. The treatment is repeated over a period of several weeks or months. It’s an outpatient procedure and considered to be safer than surgery. Transcranial magnetic stimulation (TMS) is another procedure that can help treatment-resistant depression. A magnetic coil is placed on the scalp in a medical office. An electrical current is passed through a part of the brain. Like ECT, this is not painful. This procedure is also repeated over the course of several weeks. Vagal nerve stimulation (VNS) uses an electrical stimulator in the body to activate the vagus nerve. The vagus nerve is a large nerve in the body that’s important in the parasympathetic nervous system. This is the part of the nervous system that helps the body rest and relax. This treatment requires a small procedure. A surgeon implants the stimulator in the neck, where the nerve is located. It treats both treatment-resistant depression and epilepsy. Depression has a way of making people neglect themselves. When you take time to do things you used to enjoy, even if you don’t want to at the moment, it can help your mood. Also, taking care of yourself is part of the bigger picture in your depression treatment. “I always emphasize there are three important things we do for mental health treatment,” Toledo said. Those are: Medication Psychotherapy Overall health and habits, including sleep, diet, and exercise Studies show that exercise can be helpful for treatment-resistant depression. Many people with depression have a hard time getting motivated to exercise . But research shows that exercise helps people with depression who are already taking an antidepressant. And every little bit helps. This can be as simple as moving and stretching your body more in your daily routines. Depression can feel worse when you feel physically down, too. Changing your diet and drinking enough water may help you feel better. Foods with fiber, protein, and complex carbohydrates will help to maintain your metabolism. Research on the gut-brain connection is becoming more common. This term describes how the nerves of the stomach and intestines are related to the brain. Keeping the gut healthy could help your mental health. People with depression are more likely to isolate themselves from others and experience loneliness. But research shows that increased social interaction can help with mood and loneliness. It may be difficult to be social, but spending time with loved ones — or even people you don’t know very well — can help lift you up. Look at your relationships to see if you are stuck in an unhealthy rut. Sometimes, people don’t realize how much their relationships affect their mood. These unhealthy relationships can be with partners, family, friends, or colleagues. Therapy is a good setting to work through your feelings about relationships. Don’t neglect your physical health when focused on treating your depression. Toledo also noted that it’s important to get a checkup with your primary care provider. “Maintaining overall health is important,” she said. “Your primary care provider can rule out conditions that can make depression worse. Examples are anemia, diabetes, and thyroid disease.” The bottom line Treatment-resistant depression doesn’t mean that your depression is untreatable. Trying different medications or combinations is an option. Depression can improve with therapy, exercise, and other lifestyle strategies. If you’ve heard the term “treatment resistant” describe your depression, don’t give up hope on feeling better. Many times, it’s just a matter of finding the right treatment formula that works best for you. Katherine Krive, DO, is a freelance medical writer and editor. She is also a psychiatrist who has practiced in hospital, academic, and community settings. Katie E. Golden, MD, is a board-certified emergency medicine physician and a medical editor at GoodRx. Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx. GoodRx Health has strict sourcing policies and relies on primary sources such as medical organizations, governmental agencies, academic institutions, and peer-reviewed scientific journals. Learn more about how we ensure our content is accurate, thorough, and unbiased by reading our editorial guidelines .
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[Depression](https://www.goodrx.com/conditions/depression) Depression # What Are Your Options If You Have Treatment-Resistant Depression? [![Katherine Krive, DO](https://www.grxstatic.com/4f3rgqwzdznj/1dm4QxniN8Pv1FV29c1G3Z/63b503548e50e254d09785aed218d70d/Headshot.png?w=96&q=85&fm=webp)](https://www.goodrx.com/about/bio/katherine-krive)[![Katie E. Golden, MD](https://www.grxstatic.com/4f3rgqwzdznj/491qgaKVwSdYx6oA4WaGQw/fba8bf9652d561990e7b612874ad74d6/katie_golden_goodrx.webp?w=96&q=85&fm=webp)](https://www.goodrx.com/about/bio/katie-golden) Written by [Katherine Krive, DO](https://www.goodrx.com/about/bio/katherine-krive) \\| Reviewed by [Katie E. Golden, MD](https://www.goodrx.com/about/bio/katie-golden), [Joshua Murdock, PharmD, BCBBS](https://www.goodrx.com/about/bio/joshua-murdock) Updated on April 1, 2025 ![star](https://www.grxstatic.com/images/star-with-circle.svg)![A sad client being offered a tissue box by their therapist.](https://www.grxstatic.com/4f3rgqwzdznj/434TqLhXmZw370jwseV0DY/70e43895d22b11b470513ccaa64f9a2e/offered_tissue_box_by_therapist_1436884593.jpg?w=3840&q=99&fm=webp) AnnaStills/iStock via Getty Images Plus [Definition](https://www.goodrx.com/conditions/depression/treatment-resistant-depression#definition)[Quiz](https://www.goodrx.com/conditions/depression/treatment-resistant-depression#quiz)[Medication](https://www.goodrx.com/conditions/depression/treatment-resistant-depression#medication)[Other treatments](https://www.goodrx.com/conditions/depression/treatment-resistant-depression#other-treatments)[Self-care tips](https://www.goodrx.com/conditions/depression/treatment-resistant-depression#self-care-tips)[Bottom line](https://www.goodrx.com/conditions/depression/treatment-resistant-depression#bottom-line)[References](https://www.goodrx.com/conditions/depression/treatment-resistant-depression#references) ## Key takeaways: - If you still feel depressed after trying antidepressants, you may have something called treatment-resistant depression. - Though the name may sound discouraging, treatment-resistant depression is treatable. - There are many therapies that can help with treatment-resistant depression. These include medications and nonmedication options. Have you been told that you have treatment-resistant depression? This is a term used by some healthcare professionals that can be confusing and disheartening. You may think it means that you have depression that won’t get any better. But that’s not the case at all. It just means it’s time to try something else. And you actually have many different treatment options that can help this kind of depression. ## What is treatment-resistant depression? Treatment-resistant depression refers to symptoms of depression that are ongoing even with treatment. These treatments are usually antidepressant medications. But the term “treatment-resistant depression” isn’t very useful for people with depression or even for healthcare professionals. That’s because experts don’t agree on the exact [definition](https://pubmed.ncbi.nlm.nih.gov/31638723/). Some say it’s depression that persists after a period of taking just one medication. Others say it should be diagnosed after two or three failed medication trials. Also, people can feel like the term means that their depression will never get better. They may start to lose hope after trying medications that weren’t too helpful for them. In reality, [many people](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761633/) don’t feel much better after their first or second antidepressant. Depression can be hard to treat, for many reasons: - Everyone has a unique brain that doesn’t react the same way to medication. Certain medications can be really helpful for one person and not for another, and no one knows why. - Medication can cause side effects that can make a person feel bad, like [weight gain](https://www.goodrx.com/conditions/depression/antidepressants-weight-gain) or [sexual side effects](https://www.goodrx.com/drugs/side-effects/these-drugs-may-be-affecting-your-sex-life#antidepressants). These can happen even if the medication is helping the original depression. So this can make it hard to know if the medication is helping. - There are many factors in life that affect people’s moods. Medication doesn’t address social problems or lifestyle factors that can worsen depression. But treatment-resistant depression can improve with ongoing treatment. Theresa Toledo, MD, is a psychiatrist in southeast Michigan who works with mood disorders including depression. She said that “treatment-resistant does not imply that depression cannot get better.” You and your healthcare team may want to look at different options for treatment. This can start with a change in medications. ## Quiz: Is your antidepressant working? In the past 2 weeks, have you had little interest or pleasure in doing things: - Nearly every day - More than half the days - Several days - Not at all ### In the past 2 weeks, have you felt down, depressed, or hopeless: - Nearly every day - More than half the days - Several days - Not at all ### In the past 2 weeks, have you had trouble falling asleep, staying asleep, or sleeping too much: - Nearly every day - More than half the days - Several days - Not at all ### In the past 2 weeks, have you felt tired or had little energy: - Nearly every day - More than half the days - Several days - Not at all ### In the past 2 weeks, have you had a poor appetite or overeaten: - Nearly every day - More than half the days - Several days - Not at all ### In the past 2 weeks, have you felt bad about yourself — or that you’re a failure, or have let yourself or your family down: - Nearly every day - More than half the days - Several days - Not at all ### In the past 2 weeks, have you had trouble concentrating on things, like reading or watching television: - Nearly every day - More than half the days - Several days - Not at all ### In the past 2 weeks, have you either been so slowed down or so restless that other people could have noticed: - Nearly every day - More than half the days - Several days - Not at all ### In the past 2 weeks, have you had thoughts about hurting yourself in some way, or that you would be better off dead: - Nearly every day - More than half the days - Several days - Not at all ## What medications can help treatment-resistant depression? Several kinds of medications can be useful for treatment-resistant depression. Switching to a different antidepressant can be helpful. And other types of medications can enhance the effects of an antidepressant. It’s common to use a combination of medications for treatment-resistant depression. ![GoodRx icon](https://www.grxstatic.com/images/goodrx-logo.svg) EXPERT PICKS: WHAT TO READ NEXT - Treating depression with psilocybin: Psychedelic substances like magic mushrooms are emerging as a new treatment for depression. Learn more about [how it works](https://www.goodrx.com/conditions/depression/psilocybin-and-depression). - Does magnesium help with anxiety? There’s some research to suggest [magnesium supplements](https://www.goodrx.com/well-being/supplements-herbs/magnesium-for-anxiety) can help with anxiety, depression, and trouble sleeping. - IV ketamine vs. Spravato: If you have hard-to-treat depression, ketamine may help. But it’s important to understand the [main differences in these two forms](https://www.goodrx.com/conditions/depression/iv-ketamine-vs-spravato). ### Antidepressants The most common medications used for depression are [selective serotonin reuptake inhibitors](https://www.goodrx.com/classes/ssris/ssri-list) (SSRIs). And even though they are called antidepressants, SSRIs are also prescribed for anxiety. There are several different SSRIs, and one of them may work better for you than another. Common SSRIs include: - [Citalopram](https://www.goodrx.com/citalopram/what-is) (Celexa) - [Escitalopram](https://www.goodrx.com/lexapro/what-is) (Lexapro) - [Fluoxetine](https://www.goodrx.com/prozac/what-is) (Prozac) - [Paroxetine](https://www.goodrx.com/paroxetine/what-is) (Paxil) - [Sertraline](https://www.goodrx.com/zoloft/what-is) (Zoloft) Promotion disclosure Depression medicationsCompare prices and information on the most popular Depression medications. - Lexapro Escitalopram \$11.47Lowest price [Save now](https://www.goodrx.com/lexapro) - Prozac Fluoxetine \$9.00Lowest price [Save now](https://www.goodrx.com/prozac) - Zoloft Sertraline \$12.01Lowest price [Save now](https://www.goodrx.com/zoloft) [Compare all medications](https://www.goodrx.com/conditions/depression/drugs) [Serotonin and norepinephrine reuptake inhibitors](https://www.goodrx.com/classes/snris/snri-drugs-list) (SNRIs) are another kind of antidepressant. Like SSRIs, SNRIs affect [serotonin](https://www.goodrx.com/health-topic/hormones/serotonin) in the brain, which helps to regulate mood. But they also affect [norepinephrine](https://www.goodrx.com/classes/snris/snri-side-effects). Because of this, SNRIs can be helpful for chronic pain and anxiety, too. Common SNRIs include: - [Desvenlafaxine](https://www.goodrx.com/desvenlafaxine-succinate-er/what-is) (Pristiq) - [Duloxetine](https://www.goodrx.com/cymbalta/what-is) (Cymbalta) - [Levomilnacipran](https://www.goodrx.com/fetzima/what-is) (Fetzima) - [Venlafaxine](https://www.goodrx.com/venlafaxine/what-is) (Effexor XR) There are other kinds of antidepressants that work on slightly different brain chemicals: - [Vortioxetine](https://www.goodrx.com/trintellix/what-is) (Trintellix) and [vilazodone](https://www.goodrx.com/viibryd/what-is) (Viibryd) are similar to SSRIs. But they also affect different serotonin brain receptors. - [Mirtazapine](https://www.goodrx.com/mirtazapine/what-is) (Remeron) is an antidepressant that also affects histamine. This can be helpful for sleep. - [Bupropion](https://www.goodrx.com/bupropion/what-is) (Wellbutrin SR, Wellbutrin XL) affects norepinephrine and dopamine. It can sometimes double as a [treatment for ADHD](https://www.goodrx.com/wellbutrin/how-it-works) (attention-deficit hyperactivity disorder). - [Auvelity](https://www.goodrx.com/auvelity/what-is) is a newer antidepressant that’s a combination of two medications — dextromethorphan and bupropion. Dextromethorphan affects a specific receptor in the brain called the NMDA receptor. ### Antipsychotics Adding [antipsychotic medications](https://www.goodrx.com/health-topic/mental-health/typical-vs-atypical-antipsychotics) to antidepressants can also be helpful for treatment-resistant depression. These are usually used to treat conditions such as [bipolar disorder](https://www.goodrx.com/conditions/bipolar-disorder) and [schizophrenia](https://www.goodrx.com/conditions/schizophrenia). But [lower doses](https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd-1410197717630.pdf) of these medications can be helpful in depression. The FDA has approved these antipsychotics as medications for depression: - [Aripiprazole](https://www.goodrx.com/aripiprazole/what-is) (Abilify) - [Brexpiprazole](https://www.goodrx.com/rexulti/what-is) (Rexulti) - [Cariprazine](https://www.goodrx.com/vraylar/what-is) (Vraylar) - [Olanzapine](https://www.goodrx.com/olanzapine/what-is) (Zyprexa) - [Quetiapine](https://www.goodrx.com/quetiapine/what-is) (Seroquel) - [Symbyax](https://www.goodrx.com/symbyax/what-is) (Olanzapine/fluoxetine) ### Other medications for treatment-resistant depression There are other [kinds of medications](https://www.sciencedirect.com/science/article/abs/pii/S0165032721014518?via%3Dihub) — beyond antidepressants and antipsychotics — that have also been shown to be helpful for treatment-resistant depression. [Spravato](https://www.goodrx.com/spravato/what-is) (esketamine) is a newer medication that’s FDA approved for treatment-resistant depression. It’s a form of ketamine, which is an IV medication that’s sometimes used as a [type of anesthesia](https://www.goodrx.com/conditions/anesthesia/types-of-anesthesia). The IV form of ketamine is also used for [off-label treatment](https://www.sciencedirect.com/science/article/pii/S0165178124001501) for treatment-resistant depression. But Spravato is a nasal spray that you can receive in a healthcare office. This is so your healthcare team can watch for potential side effects for a couple of hours after each dose. There are other medications that are sometimes used in addition to more common depression treatments. But it’s important to note that they aren’t officially FDA approved for depression. Because of this, they are only used in specific circumstances and with the guidance of an experienced healthcare professional: - [Lithium](https://www.goodrx.com/lithium/what-is) is usually used for stabilizing mood in bipolar disorder. It can improve mood in treatment-resistant depression, too. But blood levels need to be checked during treatment to prevent possible [lithium toxicity](https://www.goodrx.com/lithium/what-lithium-side-effects-should-you-expect#lithium-toxicity). - [Thyroid hormone](https://www.goodrx.com/synthroid/what-is) ([levothyroxine](https://www.goodrx.com/synthroid/what-is)) can also be added to antidepressants. Your prescriber will want to track your thyroid function while you’re taking this hormone. - Llisdexamfetamine ([Vyvanse](https://www.goodrx.com/vyvanse/what-is)) is a stimulant medication usually used for ADHD. It has also been shown to be helpful as an add-on for depression. - [Buspirone](https://www.goodrx.com/buspirone/what-is) (Buspar) is a medication that can sometimes be used to treat anxiety. ## What are other treatment options for treatment-resistant depression? Treatments other than medications have proved helpful for treatment-resistant depression. ### Psychotherapy Studies show that [psychotherapy](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982454/) is helpful for treatment-resistant depression. The most helpful kinds of therapy for treatment-resistant depression are: - Cognitive behavioral therapy (CBT): This well-known therapy helps you understand how you think, behave, and feel. [CBT](https://www.goodrx.com/health-topic/mental-health/cognitive-behavioral-therapy) helps you recognize and make changes to thinking patterns that contribute to depression. - Interpersonal therapy: This kind of therapy focuses on making relationships better. - Mindfulness-based cognitive therapy: Learning how to be present in the moment is a helpful way to understand and ease symptoms of depression and anxiety. Talking to a therapist is often an important part of treating depression. Therapy can help you change your mindset and the ways you go about your life. It can help you think about things differently. You may have tried therapy and felt it was not helpful. But try not to get discouraged. It may just mean you need to keep looking until you [find a therapist](https://www.goodrx.com/health-topic/mental-health/psychiatrist-vs-psychologist) who is the right fit for you. ### ECT [Electroconvulsive therapy](https://www.goodrx.com/conditions/depression/depression-ect) (ECT) is a depression treatment that uses controlled seizures. This may sound scary, but it can actually be quite effective. In fact, ECT has been named the “gold standard” for treating treatment-resistant depression. First, the person receives anesthetic medication so that they are relaxed and not aware of the seizure. Then a healthcare professional uses an electrical charge to the scalp to start a brief seizure. Since the person is asleep, this isn’t painful. The treatment is repeated over a period of several weeks or months. It’s an outpatient procedure and considered to be safer than surgery. ### TMS [Transcranial magnetic stimulation](https://www.psychologytoday.com/us/basics/transcranial-magnetic-stimulation-therapy) (TMS) is another procedure that can help treatment-resistant depression. A magnetic coil is placed on the scalp in a medical office. An electrical current is passed through a part of the brain. Like ECT, this is not painful. This procedure is also repeated over the course of several weeks. ### VNS Vagal nerve stimulation (VNS) uses an electrical stimulator in the body to activate the vagus nerve. The vagus nerve is a large nerve in the body that’s important in the parasympathetic nervous system. This is the part of the nervous system that helps the body rest and relax. This treatment requires a small procedure. A surgeon implants the stimulator in the neck, where the nerve is located. It treats both treatment-resistant depression and epilepsy. ## Self-care tips for treatment-resistant depression Depression has a way of making people neglect themselves. When you take time to do things you used to enjoy, even if you don’t want to at the moment, it can help your mood. Also, taking care of yourself is part of the bigger picture in your depression treatment. “I always emphasize there are three important things we do for mental health treatment,” Toledo said. Those are: - Medication - Psychotherapy - Overall health and habits, including sleep, diet, and exercise ### Exercise Studies show that [exercise](https://www.cambridge.org/core/journals/cns-spectrums/article/abs/exercise-as-an-addon-strategy-for-the-treatment-of-major-depressive-disorder-a-systematic-review/879856D988F804EE03393226324BA176) can be helpful for treatment-resistant depression. Many people with depression have a [hard time getting motivated to exercise](https://www.goodrx.com/well-being/movement-exercise/working-out-tired). But research shows that exercise helps people with depression who are already taking an antidepressant. And every little bit helps. This can be as simple as moving and stretching your body more in your daily routines. ### Eating well Depression can feel worse when you feel physically down, too. Changing your diet and drinking enough water may help you feel better. Foods with fiber, protein, and complex carbohydrates will help to maintain your metabolism. Research on the [gut-brain connection](https://www.goodrx.com/health-topic/mental-health/brain-gut-connection) is becoming more common. This term describes how the nerves of the stomach and intestines are related to the brain. Keeping the gut healthy could help your mental health. ### Socializing People with depression are more likely to isolate themselves from others and experience loneliness. But research shows that increased [social interaction](https://journals.sagepub.com/doi/full/10.1177/02654075211045717) can help with mood and loneliness. It may be difficult to be social, but spending time with loved ones — or even people you don’t know very well — can help lift you up. ### Relationships Look at your relationships to see if you are stuck in an unhealthy rut. Sometimes, people don’t realize how much their relationships affect their mood. These unhealthy relationships can be with partners, family, friends, or colleagues. Therapy is a good setting to work through your feelings about relationships. ### Regular healthcare visits Don’t neglect your physical health when focused on treating your depression. Toledo also noted that it’s important to get a checkup with your primary care provider. “Maintaining overall health is important,” she said. “Your primary care provider can rule out conditions that can make depression worse. Examples are anemia, diabetes, and thyroid disease.” ## The bottom line Treatment-resistant depression doesn’t mean that your depression is untreatable. Trying different medications or combinations is an option. Depression can improve with therapy, exercise, and other lifestyle strategies. If you’ve heard the term “treatment resistant” describe your depression, don’t give up hope on feeling better. Many times, it’s just a matter of finding the right treatment formula that works best for you. ![why trust our exports reliability shield](https://www.grxstatic.com/images/reliability.svg) ## Why trust our experts? ![Katherine Krive, DO](https://images.ctfassets.net/4f3rgqwzdznj/1dm4QxniN8Pv1FV29c1G3Z/63b503548e50e254d09785aed218d70d/Headshot.png) ![Katherine Krive, DO](https://images.ctfassets.net/4f3rgqwzdznj/1dm4QxniN8Pv1FV29c1G3Z/63b503548e50e254d09785aed218d70d/Headshot.png) Written by: [Katherine Krive, DO](https://www.goodrx.com/about/bio/katherine-krive) Katherine Krive, DO, is a freelance medical writer and editor. She is also a psychiatrist who has practiced in hospital, academic, and community settings. ![Katie E. Golden, MD](https://images.ctfassets.net/4f3rgqwzdznj/491qgaKVwSdYx6oA4WaGQw/fba8bf9652d561990e7b612874ad74d6/katie_golden_goodrx.webp) ![Katie E. Golden, MD](https://images.ctfassets.net/4f3rgqwzdznj/491qgaKVwSdYx6oA4WaGQw/fba8bf9652d561990e7b612874ad74d6/katie_golden_goodrx.webp) Edited by: [Katie E. Golden, MD](https://www.goodrx.com/about/bio/katie-golden) Katie E. Golden, MD, is a board-certified emergency medicine physician and a medical editor at GoodRx. ![Joshua Murdock, PharmD, BCBBS](https://images.ctfassets.net/4f3rgqwzdznj/6rpjpT3B1dTVGDH0Ws2UMg/6308582b6d1a82376657002d7a3b6ae2/joshua_murdock_goodrx.webp) ![Joshua Murdock, PharmD, BCBBS](https://images.ctfassets.net/4f3rgqwzdznj/6rpjpT3B1dTVGDH0Ws2UMg/6308582b6d1a82376657002d7a3b6ae2/joshua_murdock_goodrx.webp) Reviewed by: [Joshua Murdock, PharmD, BCBBS](https://www.goodrx.com/about/bio/joshua-murdock) Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx. ![Green trust check mark](https://www.grxstatic.com/images/green-check-mark.svg)[Our editorial standards](https://www.goodrx.com/about/editorial-guidelines) ![Green trust check mark](https://www.grxstatic.com/images/green-check-mark.svg)[Meet our experts](https://www.goodrx.com/about/health#meet-our-healthcare-experts) ## References de Sousa, R. T., et al. (2015). [Challenging treatment-resistant major depressive disorder: A roadmap for improved therapeutics](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761633/). Current Neuropharmacology. Gaynes, B. N., et al. (2020). [Defining treatment-resistant depression](https://pubmed.ncbi.nlm.nih.gov/31638723/). Depression and Anxiety. ### View All References (7) Gelenberg, A. J., et al. (2010). [Practice guidelines for the treatment of patients with major depressive disorder](https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd-1410197717630.pdf). American Psychiatric Association. Gutierrez, G., et al. (2024). [IV low dose ketamine infusions for treatment resistant depression: Results from a five-year study at a free public clinic in an academic hospital](https://www.sciencedirect.com/science/article/pii/S0165178124001501). Psychiatry Research. Kuczynski, A. M., et al. (2021). [The effect of social interaction quantity and quality on depressed mood and loneliness: A daily diary study](https://journals.sagepub.com/doi/full/10.1177/02654075211045717). Journal of Social and Personal Relationships. Mura, G., et al. (2014). [Exercise as an add-on strategy for the treatment of major depressive disorder: A systematic review](https://www.cambridge.org/core/journals/cns-spectrums/article/abs/exercise-as-an-addon-strategy-for-the-treatment-of-major-depressive-disorder-a-systematic-review/879856D988F804EE03393226324BA176). CNS Spectrums. Nuñez, N. A., et al. (2022). [Augmentation strategies for treatment resistant major depression: A systematic review and network meta-analysis](https://www.sciencedirect.com/science/article/abs/pii/S0165032721014518?via%3Dihub). Journal of Affective Disorders. Psychology Today. (n.d.). [Transcranial magnetic stimulation therapy](https://www.psychologytoday.com/us/basics/transcranial-magnetic-stimulation-therapy). Voineskos, D., et al. (2020). [Management of treatment-resistant depression: Challenges and strategies](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982454/). Neuropsychiatric Disease and Treatment. GoodRx Health has strict sourcing policies and relies on primary sources such as medical organizations, governmental agencies, academic institutions, and peer-reviewed scientific journals. Learn more about how we ensure our content is accurate, thorough, and unbiased by reading our [editorial guidelines](https://www.goodrx.com/about/editorial-guidelines). de Sousa, R. T., et al. (2015). [Challenging treatment-resistant major depressive disorder: A roadmap for improved therapeutics](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761633/). Current Neuropharmacology. Gaynes, B. N., et al. (2020). [Defining treatment-resistant depression](https://pubmed.ncbi.nlm.nih.gov/31638723/). Depression and Anxiety. Gelenberg, A. J., et al. (2010). [Practice guidelines for the treatment of patients with major depressive disorder](https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd-1410197717630.pdf). American Psychiatric Association. Gutierrez, G., et al. (2024). [IV low dose ketamine infusions for treatment resistant depression: Results from a five-year study at a free public clinic in an academic hospital](https://www.sciencedirect.com/science/article/pii/S0165178124001501). Psychiatry Research. Kuczynski, A. M., et al. (2021). [The effect of social interaction quantity and quality on depressed mood and loneliness: A daily diary study](https://journals.sagepub.com/doi/full/10.1177/02654075211045717). Journal of Social and Personal Relationships. Mura, G., et al. (2014). [Exercise as an add-on strategy for the treatment of major depressive disorder: A systematic review](https://www.cambridge.org/core/journals/cns-spectrums/article/abs/exercise-as-an-addon-strategy-for-the-treatment-of-major-depressive-disorder-a-systematic-review/879856D988F804EE03393226324BA176). CNS Spectrums. Nuñez, N. A., et al. (2022). [Augmentation strategies for treatment resistant major depression: A systematic review and network meta-analysis](https://www.sciencedirect.com/science/article/abs/pii/S0165032721014518?via%3Dihub). Journal of Affective Disorders. Psychology Today. (n.d.). [Transcranial magnetic stimulation therapy](https://www.psychologytoday.com/us/basics/transcranial-magnetic-stimulation-therapy). Voineskos, D., et al. (2020). [Management of treatment-resistant depression: Challenges and strategies](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982454/). Neuropsychiatric Disease and Treatment. ##### For additional resources or to connect with mental health services in your area, call SAMHSA’s National Helpline at [1-800-662-4357](tel:1-800-662-4357). For immediate assistance, call the [National Suicide Prevention Lifeline](https://988lifeline.org/) at [988](tel:988), or text HOME to [741-741](<sms: 741-741>) to reach the [Crisis Text Line](https://www.crisistextline.org/). ![Newsletter Subscription](https://www.grxstatic.com/images/notification-email-female.svg) #### Subscribe and save Get prescription saving tips and more from GoodRx Health. Enter your email to sign up ### Latest articles [![Health: Health Insurance: GettyImages 674796452](https://www.grxstatic.com/4f3rgqwzdznj/6EumQkAk4hmSL7NzkJu7ph/4674bf2fa9f574891bf85c3741410daa/GettyImages-674796452.webp?w=640&q=85&fm=webp) SSRIs What Is Serotonin Syndrome? 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Readable Markdown	## Key takeaways: - If you still feel depressed after trying antidepressants, you may have something called treatment-resistant depression. - Though the name may sound discouraging, treatment-resistant depression is treatable. - There are many therapies that can help with treatment-resistant depression. These include medications and nonmedication options. Have you been told that you have treatment-resistant depression? This is a term used by some healthcare professionals that can be confusing and disheartening. You may think it means that you have depression that won’t get any better. But that’s not the case at all. It just means it’s time to try something else. And you actually have many different treatment options that can help this kind of depression. Treatment-resistant depression refers to symptoms of depression that are ongoing even with treatment. These treatments are usually antidepressant medications. But the term “treatment-resistant depression” isn’t very useful for people with depression or even for healthcare professionals. That’s because experts don’t agree on the exact [definition](https://pubmed.ncbi.nlm.nih.gov/31638723/). Some say it’s depression that persists after a period of taking just one medication. Others say it should be diagnosed after two or three failed medication trials. Also, people can feel like the term means that their depression will never get better. They may start to lose hope after trying medications that weren’t too helpful for them. In reality, [many people](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761633/) don’t feel much better after their first or second antidepressant. Depression can be hard to treat, for many reasons: - Everyone has a unique brain that doesn’t react the same way to medication. Certain medications can be really helpful for one person and not for another, and no one knows why. - Medication can cause side effects that can make a person feel bad, like [weight gain](https://www.goodrx.com/conditions/depression/antidepressants-weight-gain) or [sexual side effects](https://www.goodrx.com/drugs/side-effects/these-drugs-may-be-affecting-your-sex-life#antidepressants). These can happen even if the medication is helping the original depression. So this can make it hard to know if the medication is helping. - There are many factors in life that affect people’s moods. Medication doesn’t address social problems or lifestyle factors that can worsen depression. But treatment-resistant depression can improve with ongoing treatment. Theresa Toledo, MD, is a psychiatrist in southeast Michigan who works with mood disorders including depression. She said that “treatment-resistant does not imply that depression cannot get better.” You and your healthcare team may want to look at different options for treatment. This can start with a change in medications. - Nearly every day - More than half the days - Several days - Not at all ### In the past 2 weeks, have you felt down, depressed, or hopeless: - Nearly every day - More than half the days - Several days - Not at all ### In the past 2 weeks, have you had trouble falling asleep, staying asleep, or sleeping too much: - Nearly every day - More than half the days - Several days - Not at all ### In the past 2 weeks, have you felt tired or had little energy: - Nearly every day - More than half the days - Several days - Not at all ### In the past 2 weeks, have you had a poor appetite or overeaten: - Nearly every day - More than half the days - Several days - Not at all ### In the past 2 weeks, have you felt bad about yourself — or that you’re a failure, or have let yourself or your family down: - Nearly every day - More than half the days - Several days - Not at all ### In the past 2 weeks, have you had trouble concentrating on things, like reading or watching television: - Nearly every day - More than half the days - Several days - Not at all ### In the past 2 weeks, have you either been so slowed down or so restless that other people could have noticed: - Nearly every day - More than half the days - Several days - Not at all ### In the past 2 weeks, have you had thoughts about hurting yourself in some way, or that you would be better off dead: - Nearly every day - More than half the days - Several days - Not at all Several kinds of medications can be useful for treatment-resistant depression. Switching to a different antidepressant can be helpful. And other types of medications can enhance the effects of an antidepressant. It’s common to use a combination of medications for treatment-resistant depression. The most common medications used for depression are [selective serotonin reuptake inhibitors](https://www.goodrx.com/classes/ssris/ssri-list) (SSRIs). And even though they are called antidepressants, SSRIs are also prescribed for anxiety. There are several different SSRIs, and one of them may work better for you than another. Common SSRIs include: Compare prices and information on the most popular Depression medications. [Serotonin and norepinephrine reuptake inhibitors](https://www.goodrx.com/classes/snris/snri-drugs-list) (SNRIs) are another kind of antidepressant. Like SSRIs, SNRIs affect [serotonin](https://www.goodrx.com/health-topic/hormones/serotonin) in the brain, which helps to regulate mood. But they also affect [norepinephrine](https://www.goodrx.com/classes/snris/snri-side-effects). Because of this, SNRIs can be helpful for chronic pain and anxiety, too. Common SNRIs include: There are other kinds of antidepressants that work on slightly different brain chemicals: - [Vortioxetine](https://www.goodrx.com/trintellix/what-is) (Trintellix) and [vilazodone](https://www.goodrx.com/viibryd/what-is) (Viibryd) are similar to SSRIs. But they also affect different serotonin brain receptors. - [Mirtazapine](https://www.goodrx.com/mirtazapine/what-is) (Remeron) is an antidepressant that also affects histamine. This can be helpful for sleep. - [Bupropion](https://www.goodrx.com/bupropion/what-is) (Wellbutrin SR, Wellbutrin XL) affects norepinephrine and dopamine. It can sometimes double as a [treatment for ADHD](https://www.goodrx.com/wellbutrin/how-it-works) (attention-deficit hyperactivity disorder). - [Auvelity](https://www.goodrx.com/auvelity/what-is) is a newer antidepressant that’s a combination of two medications — dextromethorphan and bupropion. Dextromethorphan affects a specific receptor in the brain called the NMDA receptor. Adding [antipsychotic medications](https://www.goodrx.com/health-topic/mental-health/typical-vs-atypical-antipsychotics) to antidepressants can also be helpful for treatment-resistant depression. These are usually used to treat conditions such as [bipolar disorder](https://www.goodrx.com/conditions/bipolar-disorder) and [schizophrenia](https://www.goodrx.com/conditions/schizophrenia). But [lower doses](https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd-1410197717630.pdf) of these medications can be helpful in depression. The FDA has approved these antipsychotics as medications for depression: - [Aripiprazole](https://www.goodrx.com/aripiprazole/what-is) (Abilify) - [Brexpiprazole](https://www.goodrx.com/rexulti/what-is) (Rexulti) - [Cariprazine](https://www.goodrx.com/vraylar/what-is) (Vraylar) - [Olanzapine](https://www.goodrx.com/olanzapine/what-is) (Zyprexa) - [Quetiapine](https://www.goodrx.com/quetiapine/what-is) (Seroquel) - [Symbyax](https://www.goodrx.com/symbyax/what-is) (Olanzapine/fluoxetine) There are other [kinds of medications](https://www.sciencedirect.com/science/article/abs/pii/S0165032721014518?via%3Dihub) — beyond antidepressants and antipsychotics — that have also been shown to be helpful for treatment-resistant depression. [Spravato](https://www.goodrx.com/spravato/what-is) (esketamine) is a newer medication that’s FDA approved for treatment-resistant depression. It’s a form of ketamine, which is an IV medication that’s sometimes used as a [type of anesthesia](https://www.goodrx.com/conditions/anesthesia/types-of-anesthesia). The IV form of ketamine is also used for [off-label treatment](https://www.sciencedirect.com/science/article/pii/S0165178124001501) for treatment-resistant depression. But Spravato is a nasal spray that you can receive in a healthcare office. This is so your healthcare team can watch for potential side effects for a couple of hours after each dose. There are other medications that are sometimes used in addition to more common depression treatments. But it’s important to note that they aren’t officially FDA approved for depression. Because of this, they are only used in specific circumstances and with the guidance of an experienced healthcare professional: - [Lithium](https://www.goodrx.com/lithium/what-is) is usually used for stabilizing mood in bipolar disorder. It can improve mood in treatment-resistant depression, too. But blood levels need to be checked during treatment to prevent possible [lithium toxicity](https://www.goodrx.com/lithium/what-lithium-side-effects-should-you-expect#lithium-toxicity). - [Thyroid hormone](https://www.goodrx.com/synthroid/what-is) ([levothyroxine](https://www.goodrx.com/synthroid/what-is)) can also be added to antidepressants. Your prescriber will want to track your thyroid function while you’re taking this hormone. - Llisdexamfetamine ([Vyvanse](https://www.goodrx.com/vyvanse/what-is)) is a stimulant medication usually used for ADHD. It has also been shown to be helpful as an add-on for depression. - [Buspirone](https://www.goodrx.com/buspirone/what-is) (Buspar) is a medication that can sometimes be used to treat anxiety. Treatments other than medications have proved helpful for treatment-resistant depression. Studies show that [psychotherapy](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982454/) is helpful for treatment-resistant depression. The most helpful kinds of therapy for treatment-resistant depression are: - Cognitive behavioral therapy (CBT): This well-known therapy helps you understand how you think, behave, and feel. [CBT](https://www.goodrx.com/health-topic/mental-health/cognitive-behavioral-therapy) helps you recognize and make changes to thinking patterns that contribute to depression. - Interpersonal therapy: This kind of therapy focuses on making relationships better. - Mindfulness-based cognitive therapy: Learning how to be present in the moment is a helpful way to understand and ease symptoms of depression and anxiety. Talking to a therapist is often an important part of treating depression. Therapy can help you change your mindset and the ways you go about your life. It can help you think about things differently. You may have tried therapy and felt it was not helpful. But try not to get discouraged. It may just mean you need to keep looking until you [find a therapist](https://www.goodrx.com/health-topic/mental-health/psychiatrist-vs-psychologist) who is the right fit for you. [Electroconvulsive therapy](https://www.goodrx.com/conditions/depression/depression-ect) (ECT) is a depression treatment that uses controlled seizures. This may sound scary, but it can actually be quite effective. In fact, ECT has been named the “gold standard” for treating treatment-resistant depression. First, the person receives anesthetic medication so that they are relaxed and not aware of the seizure. Then a healthcare professional uses an electrical charge to the scalp to start a brief seizure. Since the person is asleep, this isn’t painful. The treatment is repeated over a period of several weeks or months. It’s an outpatient procedure and considered to be safer than surgery. [Transcranial magnetic stimulation](https://www.psychologytoday.com/us/basics/transcranial-magnetic-stimulation-therapy) (TMS) is another procedure that can help treatment-resistant depression. A magnetic coil is placed on the scalp in a medical office. An electrical current is passed through a part of the brain. Like ECT, this is not painful. This procedure is also repeated over the course of several weeks. Vagal nerve stimulation (VNS) uses an electrical stimulator in the body to activate the vagus nerve. The vagus nerve is a large nerve in the body that’s important in the parasympathetic nervous system. This is the part of the nervous system that helps the body rest and relax. This treatment requires a small procedure. A surgeon implants the stimulator in the neck, where the nerve is located. It treats both treatment-resistant depression and epilepsy. Depression has a way of making people neglect themselves. When you take time to do things you used to enjoy, even if you don’t want to at the moment, it can help your mood. Also, taking care of yourself is part of the bigger picture in your depression treatment. “I always emphasize there are three important things we do for mental health treatment,” Toledo said. Those are: - Medication - Psychotherapy - Overall health and habits, including sleep, diet, and exercise Studies show that [exercise](https://www.cambridge.org/core/journals/cns-spectrums/article/abs/exercise-as-an-addon-strategy-for-the-treatment-of-major-depressive-disorder-a-systematic-review/879856D988F804EE03393226324BA176) can be helpful for treatment-resistant depression. Many people with depression have a [hard time getting motivated to exercise](https://www.goodrx.com/well-being/movement-exercise/working-out-tired). But research shows that exercise helps people with depression who are already taking an antidepressant. And every little bit helps. This can be as simple as moving and stretching your body more in your daily routines. Depression can feel worse when you feel physically down, too. Changing your diet and drinking enough water may help you feel better. Foods with fiber, protein, and complex carbohydrates will help to maintain your metabolism. Research on the [gut-brain connection](https://www.goodrx.com/health-topic/mental-health/brain-gut-connection) is becoming more common. This term describes how the nerves of the stomach and intestines are related to the brain. Keeping the gut healthy could help your mental health. People with depression are more likely to isolate themselves from others and experience loneliness. But research shows that increased [social interaction](https://journals.sagepub.com/doi/full/10.1177/02654075211045717) can help with mood and loneliness. It may be difficult to be social, but spending time with loved ones — or even people you don’t know very well — can help lift you up. Look at your relationships to see if you are stuck in an unhealthy rut. Sometimes, people don’t realize how much their relationships affect their mood. These unhealthy relationships can be with partners, family, friends, or colleagues. Therapy is a good setting to work through your feelings about relationships. Don’t neglect your physical health when focused on treating your depression. Toledo also noted that it’s important to get a checkup with your primary care provider. “Maintaining overall health is important,” she said. “Your primary care provider can rule out conditions that can make depression worse. Examples are anemia, diabetes, and thyroid disease.” ## The bottom line Treatment-resistant depression doesn’t mean that your depression is untreatable. Trying different medications or combinations is an option. Depression can improve with therapy, exercise, and other lifestyle strategies. If you’ve heard the term “treatment resistant” describe your depression, don’t give up hope on feeling better. Many times, it’s just a matter of finding the right treatment formula that works best for you. ![why trust our exports reliability shield](https://www.grxstatic.com/images/reliability.svg) ![Katherine Krive, DO](https://images.ctfassets.net/4f3rgqwzdznj/1dm4QxniN8Pv1FV29c1G3Z/63b503548e50e254d09785aed218d70d/Headshot.png) ![Katherine Krive, DO](https://images.ctfassets.net/4f3rgqwzdznj/1dm4QxniN8Pv1FV29c1G3Z/63b503548e50e254d09785aed218d70d/Headshot.png) Katherine Krive, DO, is a freelance medical writer and editor. She is also a psychiatrist who has practiced in hospital, academic, and community settings. ![Katie E. Golden, MD](https://images.ctfassets.net/4f3rgqwzdznj/491qgaKVwSdYx6oA4WaGQw/fba8bf9652d561990e7b612874ad74d6/katie_golden_goodrx.webp) ![Katie E. Golden, MD](https://images.ctfassets.net/4f3rgqwzdznj/491qgaKVwSdYx6oA4WaGQw/fba8bf9652d561990e7b612874ad74d6/katie_golden_goodrx.webp) Katie E. Golden, MD, is a board-certified emergency medicine physician and a medical editor at GoodRx. ![Joshua Murdock, PharmD, BCBBS](https://images.ctfassets.net/4f3rgqwzdznj/6rpjpT3B1dTVGDH0Ws2UMg/6308582b6d1a82376657002d7a3b6ae2/joshua_murdock_goodrx.webp) ![Joshua Murdock, PharmD, BCBBS](https://images.ctfassets.net/4f3rgqwzdznj/6rpjpT3B1dTVGDH0Ws2UMg/6308582b6d1a82376657002d7a3b6ae2/joshua_murdock_goodrx.webp) Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx. GoodRx Health has strict sourcing policies and relies on primary sources such as medical organizations, governmental agencies, academic institutions, and peer-reviewed scientific journals. Learn more about how we ensure our content is accurate, thorough, and unbiased by reading our [editorial guidelines](https://www.goodrx.com/about/editorial-guidelines).
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