Serotonin and norepinephrine reuptake inhibitors (SNRIs)

Antidepressant SNRIs help relieve depression symptoms, such as irritability and sadness, but some are also used for anxiety disorders and nerve pain. Here's how they work and what side effects they may cause.

By Mayo Clinic Staff

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a class of medications that are effective in treating depression. SNRIs are also sometimes used to treat other conditions, such as anxiety disorders and long-term (chronic) pain, especially nerve pain. SNRIs may be helpful if you have chronic pain in addition to depression.

How SNRIs work

SNRIs ease depression by affecting chemical messengers (neurotransmitters) used to communicate between brain cells. Like most antidepressants, SNRIs work by ultimately effecting changes in brain chemistry and communication in brain nerve cell circuitry known to regulate mood, to help relieve depression.

SNRIs block the reabsorption (reuptake) of the neurotransmitters serotonin (ser-o-TOE-nin) and norepinephrine (nor-ep-ih-NEF-rin) in the brain.

SNRIs approved to treat depression

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

  • Desvenlafaxine (Pristiq)
  • Duloxetine (Cymbalta) — also approved to treat anxiety and certain types of chronic pain
  • Levomilnacipran (Fetzima)
  • Venlafaxine (Effexor XR) — also approved to treat certain anxiety disorders and panic disorder

Side effects and cautions

All SNRIs work in a similar way and generally can cause similar side effects, though some people may not experience any side effects. Side effects are usually mild and go away after the first few weeks of treatment. Taking your medication with food may reduce nausea. If you can't tolerate one SNRI, you may be able to tolerate a different one, as each SNRI varies in chemical makeup.

The most common possible side effects of SNRIs include:

  • Nausea
  • Dry mouth
  • Dizziness
  • Headache
  • Excessive sweating

Other possible side effects may include:

  • Tiredness
  • Constipation
  • Insomnia
  • Changes in sexual function, such as reduced sexual desire, difficulty reaching orgasm or the inability to maintain an erection (erectile dysfunction)
  • Loss of appetite

Typically the benefits of antidepressants outweigh the possible side effects. Which antidepressant is best for you depends on a number of issues, such as your symptoms and any other health conditions you may have.

Ask your doctor and pharmacist about the most common possible side effects for your specific SNRI and read the patient medication guide that comes with the prescription.

Safety issues

SNRIs are safe for most people. However, in some circumstances they can cause problems. For example:

  • Venlafaxine, desvenlafaxine and levomilnacipran may raise your blood pressure.
  • Duloxetine may worsen liver problems.

Other issues to discuss with your doctor before you take an SNRI include:

  • Drug interactions. Tell your doctor about any other prescription or over-the-counter medications, herbs or other supplements you're taking. Some antidepressants can cause dangerous reactions when combined with certain medications or herbal products. For example, SNRIs may increase your risk of bleeding, especially when you're taking other medications that also increase the risk of bleeding, such as ibuprofen (Advil, Motrin IB, others), aspirin, warfarin (Coumadin, Jantoven) and other blood thinners.
  • Serotonin syndrome. Rarely, serotonin syndrome can occur when you take antidepressants that can cause levels of serotonin to increase in your body. This most often occurs when two medications that raise serotonin are combined, such as other antidepressants, certain pain or headache medications, or 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 symptoms.
  • Antidepressants and pregnancy. Talk with your doctor about the risks and benefits of specific antidepressants. Some antidepressants may harm your baby if you take them during pregnancy or while you're breast-feeding. If you're taking an antidepressant and considering getting pregnant, talk to your doctor about the possible risks. Don't stop taking your medication without contacting your doctor first, as stopping might pose risks for you.

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.

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 your 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 SNRIs

SNRIs are not considered addictive. However, stopping antidepressant treatment abruptly or missing several doses may cause withdrawal-like symptoms. This is sometimes called discontinuation syndrome. Withdrawal-like symptoms may be more likely to occur with venlafaxine or desvenlafaxine, though they can occur when any SNRI is stopped abruptly. Work with your doctor to gradually and safely decrease your dose.

Withdrawal-like symptoms can include:

  • Dizziness
  • Headache
  • Flu-like symptoms, such as tiredness, chills and muscle aches
  • Irritability or agitation
  • Nausea
  • Insomnia or sleep disturbances, such as nightmares
  • Diarrhea

Finding the right antidepressant

People may react differently to the same antidepressant. For example, a particular drug may work better — or not as well — for you than for another person. Or you may have more, or fewer, side effects from taking a specific antidepressant than someone else does.

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 besides genetics can affect your response to medication.

When choosing an antidepressant, your doctor takes into account your symptoms, any health problems, other medications you take and what has worked for you in the past.

Typically, 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 dose adjustments or different antidepressants, but with patience, you and your doctor can find a medication that works well for you.

Oct. 05, 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 and acupuncture
  96. Fibromyalgia: Does exercise help or hurt?
  97. Fibromyalgia: Linked to other health problems?
  98. Fibromyalgia pain: Options for coping
  99. Fibromyalgia: Self-care tips
  100. Fibromyalgia and Neurontin
  101. Fibromyalgia or not?
  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. HABIT program orientation
  107. Hangover prevention: Do lighter colored drinks help?
  108. Hangovers
  109. Hashimoto's disease
  110. Headache
  111. Hidradenitis suppurativa
  112. Hidradenitis suppurativa and biologics: Get the facts
  113. Hidradenitis suppurativa and diet: What's recommended?
  114. Hidradenitis suppurativa and sleep: How to get more zzz's
  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 (underactive thyroid)
  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. Monoamine oxidase inhibitors (MAOIs)
  177. Natural remedies for depression: Are they effective?
  178. Nervous breakdown: What does it mean?
  179. New Alzheimers Research
  180. Nicotine dependence
  181. Not tired? Don't go to bed
  182. Occipital nerve stimulation: Effective migraine treatment?
  183. Ocular migraine: When to seek help
  184. Opioids and other drugs: What to watch for
  185. Oppositional defiant disorder (ODD)
  186. Pain and depression: Is there a link?
  187. Pancreatic cancer
  188. Infographic: Pancreatic Cancer: Minimally Invasive Surgery
  189. Pancreatic Cancer Survivor
  190. Pancreatic cancer treatment: Why is it so challenging?
  191. Infographic: Pancreatic Cancers-Whipple
  192. Perimenopause
  193. Perimenopause birth control options
  194. Pet therapy
  195. Phosphatidylserine supplements: Can they improve memory?
  196. Pituitary tumors
  197. Polymyalgia rheumatica
  198. Premenstrual dysphoric disorder
  199. Premenstrual syndrome (PMS)
  200. Prescription drug abuse
  201. Prescription sleeping pills: What's right for you?
  202. Progressive supranuclear palsy
  203. Psychotherapy
  204. Rapidly progressing Alzheimer's: Something else?
  205. Reducing the discomfort of hidradenitis suppurativa: Self-care tips
  206. Salt craving: A symptom of Addison's disease?
  207. Savella may help fatigue
  208. Schizoaffective disorder
  209. Seasonal affective disorder (SAD)
  210. Choosing a light box
  211. Selective serotonin reuptake inhibitors (SSRIs)
  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