Monoamine oxidase inhibitors (MAOIs)

MAOIs were the first type of antidepressant developed. Learn about the benefits, side effects and risks of these antidepressants.

By Mayo Clinic Staff

Monoamine oxidase inhibitors (MAOIs) were the first type of antidepressant developed. They're effective, but they've generally been replaced by antidepressants that are safer and cause fewer side effects.

Use of MAOIs typically requires diet restrictions and avoiding certain other medications because MAOIs can cause dangerously high blood pressure when taken with certain foods or medications. In spite of side effects, these medications are still a good option for some people. In certain cases, they relieve depression when other treatments have failed.

How MAOIs work

Antidepressants such as MAOIs ease depression by affecting chemical messengers (neurotransmitters) used to communicate between brain cells. Like most antidepressants, MAOIs work by ultimately effecting changes in the brain chemistry that are operational in depression.

An enzyme called monoamine oxidase is involved in removing the neurotransmitters norepinephrine, serotonin and dopamine from the brain. MAOIs prevent this from happening, which makes more of these brain chemicals available to effect changes in both cells and circuits that have been impacted by depression.

MAOIs also affect other neurotransmitters in the brain and digestive system, causing side effects. MAOIs are sometimes used to treat conditions other than depression, such as Parkinson's disease.

MAOIs approved to treat depression

The Food and Drug Administration (FDA) has approved these MAOIs to treat depression:

  • Isocarboxazid (Marplan)
  • Phenelzine (Nardil)
  • Selegiline (Emsam)
  • Tranylcypromine (Parnate)

Selegiline is available as a skin (transdermal) patch. Using a patch may cause fewer side effects than MAOIs taken by mouth. If you're using the lowest dose patch, you may not need diet restrictions, but ask your doctor.

Side effects of MAOIs

Because of side effects and safety concerns, MAOIs are most often tried when other antidepressants don't work.

The most common side effects of MAOIs include:

  • Dry mouth
  • Nausea, diarrhea or constipation
  • Headache
  • Drowsiness
  • Insomnia
  • Dizziness or lightheadedness
  • Skin reaction at the patch site

Other possible side effects include:

  • Involuntary muscle jerks
  • Low blood pressure
  • Reduced sexual desire or difficulty reaching orgasm
  • Weight gain
  • Difficulty starting a urine flow
  • Muscle cramps
  • Prickling or tingling sensation in the skin (paresthesia)

Safety concerns with MAOIs

Consider these issues and discuss them with your doctor before taking an MAOI:

  • Antidepressants and pregnancy. Some antidepressants may harm your child if you take them during pregnancy or while breast-feeding. If you're considering getting pregnant, talk to your doctor or mental health provider about the possible dangers of certain antidepressants. Don't stop taking your medication without contacting your doctor first.
  • Food and beverage interactions. MAOIs can cause dangerous interactions with certain foods and beverages. You'll need to avoid foods containing high levels of tyramine ― an amino acid that regulates blood pressure ― such as aged cheeses, sauerkraut, cured meats, draft beer and fermented soy products (for example, soy sauce, miso and tofu). The interaction of tyramine with MAOIs can cause dangerously high blood pressure. Ask your doctor for a complete list of dietary restrictions, including alcohol restrictions.
  • Drug interactions. MAOIs can cause serious reactions when you take them with certain medications, such as other antidepressants, certain pain drugs, certain cold and allergy medications, and some herbal supplements. Always check with your doctor or pharmacist before taking any other prescription or over-the-counter medication, herbs or other supplements while you're taking an MAOI.
  • Serotonin syndrome. Rarely, an MAOI can cause dangerously high levels of serotonin, known as serotonin syndrome. It most often occurs when two medications that raise serotonin are combined. These include, for example, other antidepressants, certain pain or headache medications, and the herbal supplement St. John's wort.
    • Signs and symptoms of serotonin syndrome include anxiety, agitation, high fever, sweating, confusion, tremors, restlessness, lack of coordination, major changes in blood pressure, and rapid heart rate. Seek immediate medical attention if you have any of these signs or symptoms.

Suicide risk and antidepressants

Most antidepressants are generally safe, but the FDA requires that all antidepressants carry black box warnings, the strictest warnings for prescriptions. In some cases, children, teenagers and young adults under 25 may have an increase in suicidal thoughts or behavior when taking antidepressants, especially in the first few weeks after starting or when the dose is changed.

MAOIs are generally not prescribed for children, but anyone taking an antidepressant should be watched closely for worsening depression or unusual behavior. If you or someone you know has suicidal thoughts when taking an antidepressant, immediately contact a doctor or get emergency help.

Keep in mind that antidepressants are more likely to reduce suicide risk in the long run by improving mood.

Stopping treatment with MAOIs

Talk to your doctor before you stop taking an MAOI. Stopping treatment with MAOIs has been associated with anxiety, agitation and insomnia, as well as flu-like symptoms such as sweating, chills, nausea, headache and feeling generally unwell (malaise).

If you stop an MAOI suddenly, you're more likely to experience a withdrawal-type reaction, sometimes called discontinuation syndrome. Rarely, uncommon withdrawal symptoms such as confusion, detachment from reality (psychosis) and convulsions can occur.

You may need to wait two or more weeks between the use of MAOIs and other antidepressants to avoid serotonin syndrome. During those two weeks, you should continue food and beverage restrictions and avoid taking drugs that can cause serious interactions with MAOIs.

Work with your doctor to gradually and safely decrease your dose.

Finding the right antidepressant

Each person reacts differently to a particular antidepressant and may be more likely to have certain side effects. Because of this, one antidepressant may work better for you than another. When choosing an antidepressant, your doctor takes into account your symptoms, any health problems you have, other medications you take and what has worked for you in the past.

Inherited traits play a role in how antidepressants affect you. In some cases, where available, results of special blood tests may offer clues about how your body may respond to a particular antidepressant. However, other variables can affect your response to medication.

It may take several weeks or longer before an antidepressant is fully effective and for initial side effects to ease up. Your doctor may recommend some dose adjustments or different antidepressants, but with patience, you and your doctor can find a medication that works well for you.

Sept. 12, 2019 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 depression: Coping with the two conditions
  86. Diagnosing Alzheimer's
  87. Dissociative disorders
  88. Vitamin C and mood
  89. Drug addiction (substance use disorder)
  90. Alzheimer's elder care
  91. Electroconvulsive therapy (ECT)
  92. Empty nest syndrome
  93. Fatigue
  94. Fibromyalgia
  95. Fibromyalgia or not?
  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. Fish oil and depression
  103. Folic acid supplements: Can they slow cognitive decline?
  104. Foods and sleep
  105. Ginkgo biloba: Can it prevent memory loss?
  106. Global Bridges
  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: Tips for weight-loss success
  116. Hidradenitis suppurativa: What is it?
  117. Hidradenitis suppurativa: When does it appear?
  118. Hidradenitis suppurativa: Where can I find support?
  119. How opioid addiction occurs
  120. How to tell if a loved one is abusing opioids
  121. How to use opioids safely
  122. Huperzine A: Can it treat Alzheimer's?
  123. Hyperparathyroidism
  124. Hypoparathyroidism
  125. Hypothyroidism: Can calcium supplements interfere with treatment?
  126. Hypothyroidism diet
  127. Hypothyroidism and joint pain?
  128. Hypothyroidism: Should I take iodine supplements?
  129. Hypothyroidism symptoms: Can hypothyroidism cause eye problems?
  130. Hypothyroidism
  131. Insomnia
  132. Insomnia: How do I stay asleep?
  133. Insomnia treatment: Cognitive behavioral therapy instead of sleeping pills
  134. Intervention: Help a loved one overcome addiction
  135. Is depression a factor in rheumatoid arthritis?
  136. Is fibromyalgia hereditary?
  137. Is the definition of Alzheimer's disease changing?
  138. Depression and diet
  139. Kratom for opioid withdrawal
  140. Lack of sleep: Can it make you sick?
  141. Lexapro side effects: Is breast tenderness common?
  142. Living better with hidradenitis suppurativa
  143. Low blood pressure (hypotension)
  144. Male depression: Understanding the issues
  145. Managing depression in MS
  146. Managing Headaches
  147. Managing hidradenitis suppurativa: Early treatment is crucial
  148. Hidradenitis suppurativa-related health risks
  149. MAOIs and diet: Is it necessary to restrict tyramine?
  150. Marijuana and depression
  151. Mayo Clinic Minute: 3 tips to reduce your risk of Alzheimer's disease
  152. Mayo Clinic Minute: Alzheimer's disease risk and lifestyle
  153. Mayo Clinic Minute New definition of Alzheimer's changes
  154. Mayo Clinic Minute: Prevent migraines with magnetic stimulation
  155. Mayo Clinic Minute Weathering migraines
  156. Mayo Clinic Minute: Women and Alzheimer's Disease
  157. Medication overuse headaches
  158. Meditation
  159. Mediterranean diet recipes
  160. Memory loss: When to seek help
  161. Mental health: Overcoming the stigma of mental illness
  162. Mental health providers: Tips on finding one
  163. Mental health
  164. Mental illness
  165. Migraine
  166. Migraine medications and antidepressants
  167. Migraine treatment: Can antidepressants help?
  168. Infographic: Migraine Treatments: Botox & Nerve Blocking
  169. Migraines and gastrointestinal problems: Is there a link?
  170. Migraines and Vertigo
  171. Migraines: Are they triggered by weather changes?
  172. Alleviating migraine pain
  173. Mild cognitive impairment (MCI)
  174. Mild depression: Are antidepressants effective?
  175. Mindfulness exercises
  176. Natural remedies for depression: Are they effective?
  177. Nervous breakdown: What does it mean?
  178. New Alzheimers Research
  179. Nicotine dependence
  180. Not tired? Don't go to bed
  181. Occipital nerve stimulation: Effective migraine treatment?
  182. Ocular migraine: When to seek help
  183. Opioids and other drugs: What to watch for
  184. Oppositional defiant disorder (ODD)
  185. Pain and depression: Is there a link?
  186. Pancreatic cancer
  187. Infographic: Pancreatic Cancer: Minimally Invasive Surgery
  188. Pancreatic Cancer Survivor
  189. Pancreatic cancer treatment: Why is it so challenging?
  190. Infographic: Pancreatic Cancers-Whipple
  191. Perimenopause
  192. Perimenopause birth control options
  193. Pet therapy
  194. Phosphatidylserine supplements: Can they improve memory?
  195. Pituitary tumors
  196. Polymyalgia rheumatica
  197. Premenstrual dysphoric disorder
  198. Premenstrual syndrome (PMS)
  199. Prescription drug abuse
  200. Prescription sleeping pills: What's right for you?
  201. Progressive supranuclear palsy
  202. Psychotherapy
  203. Rapidly progressing Alzheimer's: Something else?
  204. Reducing the discomfort of hidradenitis suppurativa: Self-care tips
  205. Salt craving: A symptom of Addison's disease?
  206. Savella may help fatigue
  207. Schizoaffective disorder
  208. Seasonal affective disorder (SAD)
  209. Choosing a light box
  210. Selective serotonin reuptake inhibitors (SSRIs)
  211. Serotonin and norepinephrine reuptake inhibitors (SNRIs)
  212. Skip booze for better sleep
  213. Sleep disorders
  214. Sleep tips
  215. Smoking and rheumatoid arthritis: What's the risk?
  216. Soy: Does it worsen hypothyroidism?
  217. Staying active with hidradenitis suppurativa
  218. Stop your next migraine before it starts
  219. Stress symptoms
  220. Sundowning: Late-day confusion
  221. Support groups
  222. Surgery for hidradenitis suppurativa
  223. Symptom Checker
  224. Tapering off opioids: When and how
  225. Tinnitus and antidepressants
  226. Transcranial magnetic stimulation
  227. Traumatic brain injury
  228. Treating hidradenitis suppurativa: Explore your options
  229. Treating hidradenitis suppurativa with antibiotics and hormones
  230. Treating pain: When is an opioid the right choice?
  231. Treatment-resistant depression
  232. Tricyclic antidepressants and tetracyclic antidepressants
  233. Unexplained weight loss
  234. Vagus nerve stimulation
  235. Valerian: A safe and effective herbal sleep aid?
  236. Vascular dementia
  237. Video: Alzheimer's drug shows early promise
  238. Video: Vagus nerve stimulation
  239. Vitamin B-12 and depression
  240. Vitamin B-12 and Alzheimer's
  241. Vitamin D: Can it prevent Alzheimer's & dementia?
  242. What are opioids and why are they dangerous?
  243. What are the signs and symptoms of hidradenitis suppurativa?
  244. What is reflexology?
  245. Wilson's disease
  246. Wilson's syndrome: An accepted medical diagnosis?
  247. Young-onset Alzheimer's