Treatment-resistant depression

Sometimes depression doesn't get better, even with treatment. Explore what you can do about it.

By Mayo Clinic Staff

If you've been treated for depression but your symptoms haven't improved, you may have treatment-resistant depression. Taking an antidepressant or going to psychological counseling (psychotherapy) eases depression symptoms for most people. But with treatment-resistant depression, standard treatments aren't enough. They may not help much at all, or your symptoms may improve, only to keep coming back.

If your primary care doctor prescribed antidepressants and your depression symptoms continue despite treatment, ask your doctor if he or she can recommend a health care provider who specializes in diagnosing and treating mental health conditions.

The psychiatrist reviews your medical history and may:

  • Ask about life situations that might be contributing to your depression
  • Consider your response to treatment, including medications, psychotherapy or other treatments you've tried
  • Review all of the medications you're taking, including nonprescription drugs and herbal supplements
  • Discuss whether you're taking your medications as prescribed and following other treatment steps
  • Consider physical health conditions that can sometimes cause or worsen depression, such as thyroid disorders, chronic pain or heart problems
  • Consider a diagnosis of another mental health condition, such as bipolar disorder, which can cause or worsen depression and may require different treatment; dysthymia, a mild but long-term (chronic) form of depression; or a personality disorder that contributes to the depression not getting better

Treatment-resistant depression symptoms can range from mild to severe and may require trying a number of approaches to identify what helps.

Medication strategies

If you've already tried an antidepressant and it didn't work, don't lose hope. You and your physician simply may not have found the right dose, medication or combination of medications that works for you. Here are some medication options that your doctor may discuss with you:

  • Give your current medications more time. Antidepressants and other medications for depression typically take four to eight weeks to become fully effective and for side effects to ease up. For some people, it takes even longer.
  • Increase your dose, if indicated. Because people respond to medications differently, you may benefit from a higher dose of medication than is usually prescribed. Ask your doctor whether this is an option for you — don't change your dose on your own as several factors are involved in determining the proper dose.
  • Switch antidepressants. For a number of people, the first antidepressant tried isn't effective. You may need to try several before you find one that works for you.
  • Add another type of antidepressant. Your doctor may prescribe two different classes of antidepressants at the same time. That way they'll affect a wider range of brain chemicals linked to mood. These chemicals are neurotransmitters that include dopamine, serotonin and norepinephrine.
  • Add a medication generally used for another condition. Your doctor may prescribe a medication that's generally used for another mental or physical health problem, along with an antidepressant. This approach, known as augmentation, may include antipsychotics, mood stabilizers, anti-anxiety medications, thyroid hormone or other drugs.
  • Consider pharmacogenetic testing. These tests check for specific genes that indicate how well your body can process (metabolize) a medication or how your depression might respond to a particular medication based on additional factors. Currently, pharmacogenetics tests are not a sure way to show if a medication will work for you, but these tests can provide important clues for treatment, particularly in people who have many side effects or have had poor results with certain medications. These tests are not always covered by insurance.

Psychological counseling

Psychological counseling (psychotherapy) by a psychiatrist, psychologist or other mental health professional can be very effective. For many people, psychotherapy combined with medication works best. It can help identify underlying concerns that may be adding to your depression. In working with your therapist, you can also learn specific behaviors and strategies to overcome your depression. For example, psychotherapy can help you:

  • Find better ways to cope with life's challenges
  • Deal with past emotional trauma
  • Manage relationships in a healthier way
  • Learn how to reduce the effects of stress in your life
  • Address substance use issues

If counseling doesn't seem helpful, talk to your psychotherapist about trying a different approach. Or consider seeing someone else. As with medications, it may take several tries to find a treatment that works. Psychotherapy for depression may include:

  • Cognitive behavioral therapy. This common type of counseling addresses thoughts, feelings and behaviors that affect your mood. It helps you identify and change distorted or negative thinking patterns and teaches you skills to respond to life's challenges in a positive way.
  • Acceptance and commitment therapy. A form of cognitive behavioral therapy, acceptance and commitment therapy helps you to engage in positive behaviors, even when you have negative thoughts and emotions. It's designed for treatment-resistant conditions.
  • Interpersonal psychotherapy. Interpersonal psychotherapy focuses on resolving relationship issues that may contribute to your depression.
  • Family or marital therapy. This type of therapy involves family members or your spouse or partner in counseling. Working out stress in your relationships can help with depression.
  • Dialectical behavioral therapy. This type of therapy helps you build acceptance strategies and problem-solving skills. This is useful for chronic suicidal thoughts or self-injury behaviors, which sometimes accompany treatment-resistant depression.
  • Group psychotherapy. This type of counseling involves a group of people who struggle with depression working together with a psychotherapist.
  • Mindfulness. Mindfulness involves paying attention and accepting one's thoughts and feelings without judging them as "right" or "wrong" in a given moment.
  • Behavioral activation. This type of treatment works with depressed individuals to gradually decrease their avoidance and isolation and increase their engagement in activities that they once enjoyed or activities that have been shown to improve mood.

Procedures to treat depression

If medications and psychotherapy aren't working, you may want to talk to a psychiatrist about additional treatment options:

  • Repetitive transcranial magnetic stimulation (rTMS). This type of treatment uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of depression. An electromagnetic coil is placed against your scalp near your forehead. The electromagnet used in rTMS creates electric currents that stimulate nerve cells in the region of your brain involved in mood control and depression. Typically, this treatment is delivered over 30-minute sessions in rapid bursts. This treatment can now be delivered over briefer sessions with dosing called intermittent theta burst stimulation.
  • Ketamine is a medication that's delivered through an IV in low doses. It's used for rapid relief of hard-to-treat depressive symptoms and its effects can last from days to weeks. Usually it's given in decreasing frequencies over several weeks. The FDA approved an intranasal form called esketamine that's given in a physician's office or a clinic under the supervision of a health care provider to monitor for possible serious side effects and because of the potential for abuse and misuse. Esketamine is for adults who have tried at least two other antidepressant medications that did not adequately control symptoms. Ketamine and esketamine work in the brain in a different way than standard antidepressants, and each is typically used along with an oral antidepressant.
  • Electroconvulsive therapy (ECT). While you're asleep, a carefully measured dose of electricity is passed through your brain, intentionally triggering a small, brief seizure. ECT seems to cause changes in brain chemistry that can relatively quickly reverse symptoms of major depression. Although there are potential side effects, such as temporary confusion or temporary memory loss, a series of ECT treatments may provide significant relief of severe depression.
  • Vagus nerve stimulation (VNS). Generally, VNS is only tried after other brain stimulation therapies such as ECT and rTMS have not been successful in improving symptoms of depression. VNS stimulates the vagus nerve with electrical impulses. This treatment uses a device implanted in your chest that's connected by a wire to a nerve in your neck (vagus nerve). Electrical signals from the implant travel along the vagus nerve to the mood centers of the brain, which may improve depression symptoms.

Be sure to find out whether your insurance covers any treatment that's recommended.

Other steps you can take

To make the most of depression treatment:

  • Stick to your treatment plan. Don't skip therapy sessions or appointments. It'll take time to get better. Even if you feel well, don't skip your medications. If you stop, depression symptoms may come back, and you could experience withdrawal-like symptoms. If side effects or drug costs are a problem, talk with your doctor and pharmacist to discuss options.
  • Stop drinking or using recreational drugs. Many people with depression drink too much alcohol or use recreational drugs or marijuana. In the long run, alcohol and drugs worsen depression and make it harder to treat. If you can't stop drinking alcohol or using drugs on your own, talk to your doctor or mental health professional. Depression treatment may be unsuccessful until you address your substance use.
  • Manage stress. Relationship issues, financial problems, an unhappy work life and many other issues can all contribute to stress, which in turn worsens depression. Try stress-reduction techniques such as yoga, tai chi, meditation, mindfulness, progressive muscle relaxation or writing your thoughts in a journal.
  • Sleep well. Poor sleep may worsen depression. Both the amount of time and how well you sleep can affect your mood, energy level, ability to concentrate and resilience to stress. If you have trouble sleeping, research ways to improve your sleep habits or ask your doctor or mental health professional for advice.
  • Get regular exercise. Exercise has a direct effect on mood. Even physical activity such as gardening or walking can reduce stress, improve sleep and ease depression symptoms.

Don't settle for a treatment that's partially effective at relieving your depression or one that works but causes intolerable side effects. Work with your doctor or other mental health professional to find the best treatment possible, even though it may take time and effort to try new approaches.

April 10, 2021 See more In-depth

See also

  1. MIND diet may cut Alzheimer's risk
  2. Addison's disease
  3. Adjustment disorders
  4. Adrenal fatigue: What causes it?
  5. After a flood, are food and medicines safe to use?
  6. Alzheimer's: New treatments
  7. Alzheimer's 101
  8. Caregiver depression
  9. Understanding the difference between dementia types
  10. Alzheimer's: Can a head injury increase my risk?
  11. Mediterranean diet
  12. Alzheimer's disease
  13. Alzheimer's disease: Can exercise prevent memory loss?
  14. Alzheimer's drugs
  15. Alzheimer's genes
  16. Alzheimer's nose spray: New Alzheimer's treatment?
  17. Alzheimer's or depression: Could it be both?
  18. Alzheimer's prevention: Does it exist?
  19. Alzheimer's stages
  20. Alzheimer's test: Detection at the earliest stages
  21. Ambien: Is dependence a concern?
  22. Antidepressant withdrawal: Is there such a thing?
  23. Antidepressants and alcohol: What's the concern?
  24. Antidepressants and weight gain: What causes it?
  25. Antidepressants: Can they stop working?
  26. Antidepressants: Side effects
  27. Antidepressants: Selecting one that's right for you
  28. Antidepressants: Which cause the fewest sexual side effects?
  29. Antiphospholipid syndrome
  30. Antidepressants and pregnancy
  31. Atypical antidepressants
  32. Atypical depression
  33. Axona: Medical food to treat Alzheimer's
  34. Back pain
  35. Bedtime routines: Not just for babies
  36. Benefits of being bilingual
  37. Binge-eating disorder
  38. Blood Basics
  39. Borderline personality disorder
  40. Breast-feeding and medications
  41. Dr. Wallace Video
  42. Parathyroid
  43. Caffeine and depression: Is there a link?
  44. The role of diet and exercise in preventing Alzheimer's disease
  45. Can music help someone with Alzheimer's?
  46. Can zinc supplements help treat hidradenitis suppurativa?
  47. Can't sleep? Try daytime exercise
  48. Hidradenitis suppurativa wound care
  49. Celiac disease
  50. Celiac disease: Can gluten be absorbed through the skin?
  51. Celiac disease diet: How do I get enough grains?
  52. Chase away the winter blues
  53. Child abuse
  54. Chronic traumatic encephalopathy
  55. CJD - Creutzfeldt-Jakob Disease
  56. Clinical depression: What does that mean?
  57. Clinical trials for hidradenitis suppurativa
  58. Coconut oil: Can it cure hypothyroidism?
  59. Coffee after dinner? Make it decaf
  60. Complete blood count (CBC)
  61. Complicated grief
  62. Compulsive sexual behavior
  63. Concussion
  64. Concussion in children
  65. Concussion Recovery
  66. Concussion Telemedicine
  67. Coping with the stress of hidradenitis suppurativa
  68. Coping with the emotional ups and downs of psoriatic arthritis
  69. COVID-19 and your mental health
  70. Coping with unemployment caused by COVID-19
  71. Creating a hidradenitis suppurativa care team
  72. Creutzfeldt-Jakob disease
  73. Cupping therapy: Can it relieve fibromyalgia pain?
  74. Cushing syndrome
  75. Cyclothymia (cyclothymic disorder)
  76. Delirium
  77. Depression and anxiety: Can I have both?
  78. Depression, anxiety and exercise
  79. Depression: Diagnosis is key
  80. Depression during pregnancy
  81. Depression in women: Understanding the gender gap
  82. Depression (major depressive disorder)
  83. Depression: Provide support, encouragement
  84. Depression: Supporting a family member or friend
  85. Diabetes and Alzheimer's
  86. Diabetes and depression: Coping with the two conditions
  87. Diagnosing Alzheimer's
  88. Dissociative disorders
  89. Vitamin C and mood
  90. Drug addiction (substance use disorder)
  91. Alzheimer's elder care
  92. Electroconvulsive therapy (ECT)
  93. Empty nest syndrome
  94. Fatigue
  95. Fibromyalgia
  96. Fibromyalgia and acupuncture
  97. Fibromyalgia: Does exercise help or hurt?
  98. Fibromyalgia: Linked to other health problems?
  99. Fibromyalgia pain: Options for coping
  100. Fibromyalgia: Self-care tips
  101. Fibromyalgia and Neurontin
  102. Fibromyalgia or not?
  103. Fish oil and depression
  104. Folic acid supplements: Can they slow cognitive decline?
  105. Foods and sleep
  106. Ginkgo biloba: Can it prevent memory loss?
  107. HABIT program orientation
  108. Hangover prevention: Do lighter colored drinks help?
  109. Hangovers
  110. Hashimoto's disease
  111. Headache
  112. Hidradenitis suppurativa
  113. Hidradenitis suppurativa and biologics: Get the facts
  114. Hidradenitis suppurativa and diet: What's recommended?
  115. Hidradenitis suppurativa and sleep: How to get more zzz's
  116. Hidradenitis suppurativa: Tips for weight-loss success
  117. Hidradenitis suppurativa: What is it?
  118. Hidradenitis suppurativa: When does it appear?
  119. Hidradenitis suppurativa: Where can I find support?
  120. How opioid addiction occurs
  121. How to tell if a loved one is abusing opioids
  122. How to use opioids safely
  123. Huperzine A: Can it treat Alzheimer's?
  124. Hyperparathyroidism
  125. Hypoparathyroidism
  126. Hypothyroidism: Can calcium supplements interfere with treatment?
  127. Hypothyroidism diet
  128. Hypothyroidism and joint pain?
  129. Hypothyroidism: Should I take iodine supplements?
  130. Hypothyroidism symptoms: Can hypothyroidism cause eye problems?
  131. Hypothyroidism (underactive thyroid)
  132. Insomnia
  133. Insomnia: How do I stay asleep?
  134. Insomnia treatment: Cognitive behavioral therapy instead of sleeping pills
  135. Intervention: Help a loved one overcome addiction
  136. Is depression a factor in rheumatoid arthritis?
  137. Is fibromyalgia hereditary?
  138. Is the definition of Alzheimer's disease changing?
  139. Depression and diet
  140. Kratom for opioid withdrawal
  141. Lack of sleep: Can it make you sick?
  142. Lexapro side effects: Is breast tenderness common?
  143. Living better with hidradenitis suppurativa
  144. Low blood pressure (hypotension)
  145. Male depression: Understanding the issues
  146. Managing depression in MS
  147. Managing Headaches
  148. Managing hidradenitis suppurativa: Early treatment is crucial
  149. Hidradenitis suppurativa-related health risks
  150. MAOIs and diet: Is it necessary to restrict tyramine?
  151. Marijuana and depression
  152. Mayo Clinic Minute: 3 tips to reduce your risk of Alzheimer's disease
  153. Mayo Clinic Minute: Alzheimer's disease risk and lifestyle
  154. Mayo Clinic Minute New definition of Alzheimer's changes
  155. Mayo Clinic Minute: Prevent migraines with magnetic stimulation
  156. Mayo Clinic Minute Weathering migraines
  157. Mayo Clinic Minute: Women and Alzheimer's Disease
  158. Medication overuse headaches
  159. Meditation
  160. Mediterranean diet recipes
  161. Memory loss: When to seek help
  162. Mental health: Overcoming the stigma of mental illness
  163. Mental health providers: Tips on finding one
  164. Mental health
  165. Mental illness
  166. Migraine
  167. Migraine medications and antidepressants
  168. Migraine treatment: Can antidepressants help?
  169. Infographic: Migraine Treatments: Botox & Nerve Blocking
  170. Migraines and gastrointestinal problems: Is there a link?
  171. Migraines and Vertigo
  172. Migraines: Are they triggered by weather changes?
  173. Alleviating migraine pain
  174. Mild cognitive impairment (MCI)
  175. Mild depression: Are antidepressants effective?
  176. Mindfulness exercises
  177. Monoamine oxidase inhibitors (MAOIs)
  178. Natural remedies for depression: Are they effective?
  179. Nervous breakdown: What does it mean?
  180. New Alzheimers Research
  181. Nicotine dependence
  182. Not tired? Don't go to bed
  183. Occipital nerve stimulation: Effective migraine treatment?
  184. Ocular migraine: When to seek help
  185. Opioids and other drugs: What to watch for
  186. Oppositional defiant disorder (ODD)
  187. Pain and depression: Is there a link?
  188. Pancreatic cancer
  189. Infographic: Pancreatic Cancer: Minimally Invasive Surgery
  190. Pancreatic Cancer Survivor
  191. Pancreatic cancer treatment: Why is it so challenging?
  192. Infographic: Pancreatic Cancers-Whipple
  193. Perimenopause
  194. Perimenopause birth control options
  195. Pet therapy
  196. Phosphatidylserine supplements: Can they improve memory?
  197. Pituitary tumors
  198. Polymyalgia rheumatica
  199. Premenstrual dysphoric disorder
  200. Premenstrual syndrome (PMS)
  201. Prescription drug abuse
  202. Prescription sleeping pills: What's right for you?
  203. Progressive supranuclear palsy
  204. Psychotherapy
  205. Rapidly progressing Alzheimer's: Something else?
  206. Reducing the discomfort of hidradenitis suppurativa: Self-care tips
  207. Salt craving: A symptom of Addison's disease?
  208. Savella may help fatigue
  209. Schizoaffective disorder
  210. Seasonal affective disorder (SAD)
  211. Choosing a light box
  212. Selective serotonin reuptake inhibitors (SSRIs)
  213. Serotonin and norepinephrine reuptake inhibitors (SNRIs)
  214. Skip booze for better sleep
  215. Sleep disorders
  216. Sleep tips
  217. Smoking and rheumatoid arthritis: What's the risk?
  218. Soy: Does it worsen hypothyroidism?
  219. Staying active with hidradenitis suppurativa
  220. Stop your next migraine before it starts
  221. Stress symptoms
  222. Sundowning: Late-day confusion
  223. Support groups
  224. Surgery for hidradenitis suppurativa
  225. Symptom Checker
  226. Tapering off opioids: When and how
  227. Tinnitus and antidepressants
  228. Transcranial magnetic stimulation
  229. Traumatic brain injury
  230. Treating hidradenitis suppurativa: Explore your options
  231. Treating hidradenitis suppurativa with antibiotics and hormones
  232. Treating pain: When is an opioid the right choice?
  233. Tricyclic antidepressants and tetracyclic antidepressants
  234. Unexplained weight loss
  235. Vagus nerve stimulation
  236. Valerian: A safe and effective herbal sleep aid?
  237. Vascular dementia
  238. Video: Alzheimer's drug shows early promise
  239. Video: Vagus nerve stimulation
  240. Vitamin B-12 and depression
  241. Vitamin B-12 and Alzheimer's
  242. Vitamin D: Can it prevent Alzheimer's & dementia?
  243. What are opioids and why are they dangerous?
  244. What are the signs and symptoms of hidradenitis suppurativa?
  245. What is reflexology?
  246. Wilson's disease
  247. Wilson's syndrome: An accepted medical diagnosis?
  248. Young-onset Alzheimer's