Which of the following is a neurotransmitter that is targeted by various antidepressant and antipsychotic drugs?

Tricyclic antidepressants and tetracyclic antidepressants

Tricyclic and tetracyclic antidepressants affect brain chemicals to ease depression symptoms. Explore their possible side effects and whether one of these antidepressants may be a good option for you.

By Mayo Clinic Staff

Tricyclic and tetracyclic antidepressants, also called cyclic antidepressants, are among the earliest antidepressants developed. They're effective, but they've generally been replaced by antidepressants that cause fewer side effects. However, cyclic antidepressants may be a good option for some people. In certain cases, they relieve depression when other treatments have failed.

Cyclic antidepressants are designated as tricyclic or tetracyclic, depending on the number of rings in their chemical structure — three (tri) or four (tetra).

How cyclic antidepressants work

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

Cyclic antidepressants block the reabsorption (reuptake) of the neurotransmitters serotonin (ser-o-TOE-nin) and norepinephrine (nor-ep-ih-NEF-rin), increasing the levels of these two neurotransmitters in the brain. Cyclic antidepressants also affect other chemical messengers, which can lead to a number of side effects.

Cyclic antidepressants approved to treat depression

The Food and Drug Administration (FDA) approved these tricyclic antidepressants to treat depression:

  • Amitriptyline
  • Amoxapine
  • Desipramine (Norpramin)
  • Doxepin
  • Imipramine (Tofranil)
  • Nortriptyline (Pamelor)
  • Protriptyline
  • Trimipramine

The FDA approved the tetracyclic antidepressant maprotiline to treat depression.

Sometimes cyclic antidepressants are used to treat conditions other than depression, such as obsessive-compulsive disorder, anxiety disorders or nerve-related (neuropathic) pain.

Possible side effects and cautions

Because of the different ways cyclic antidepressants work, side effects vary somewhat from medication to medication. Some side effects may go away after a time, while others may lead you and your doctor to try a different medication. Side effects may also be dependent on the dose, with higher doses often causing more side effects.

Some common possible side effects include:

  • Drowsiness
  • Blurred vision
  • Constipation
  • Dry mouth
  • Drop in blood pressure when moving from sitting to standing, which can cause lightheadedness
  • Urine retention

Other possible side effects include:

  • Weight loss
  • Increased appetite leading to weight gain
  • Excessive sweating
  • Tremor
  • Sexual problems, such as difficulty achieving an erection, delayed orgasm or low sex drive

Generally speaking:

  • Amitriptyline, doxepin, imipramine and trimipramine are more likely to make you sleepy than other tricyclic antidepressants are. Taking these medications at bedtime may help.
  • Amitriptyline, doxepin, imipramine and trimipramine are more likely to cause weight gain than other tricyclic antidepressants are.
  • Nortriptyline and desipramine appear to have better tolerated side effects than other tricyclic antidepressants do.

For antidepressants that cause sleepiness, be careful about doing activities that require you to be alert, such as driving a car, until you know how the medication will affect you.

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 antidepressant and read the patient medication guide that comes with the prescription.

Safety issues

Some tricyclic antidepressants are more likely to cause side effects that affect safety, such as:

  • Disorientation or confusion, particularly in older people when the dosage is too high
  • Increased or irregular heart rate
  • More-frequent seizures in people who have seizures

Other issues to discuss with your doctor before you take a cyclic antidepressant:

  • Antidepressants and pregnancy. Talk to your doctor about the risks and benefits of using 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 you're considering getting pregnant, talk to your doctor or mental health professional about the possible risks. Don't stop taking your medication without contacting your doctor first, as stopping might pose risks for you.
  • Drug interactions. When taking an antidepressant, 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 supplements.
  • Serotonin syndrome. Rarely, an antidepressant can cause high levels of serotonin to accumulate in your body. Serotonin syndrome most often occurs when two medications that raise the level of serotonin are combined. These include 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 a rapid heart rate.
    • Seek immediate medical attention if you have any of these signs and symptoms.
  • Safety and blood tests. Your doctor may recommend blood levels to determine the most effective dose. Some side effects and benefits of cyclic antidepressants depend on the dose. Overdose of cyclic antidepressants can be dangerous.
  • Chronic health conditions. Cyclic antidepressants can cause problems in people with certain health conditions. For example, if you have glaucoma, an enlarged prostate, heart problems, diabetes, liver disease or a history of seizures, talk to your doctor about whether a cyclic antidepressant is a safe choice 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 cyclic antidepressants

Cyclic antidepressants aren't considered addictive. However, stopping antidepressant treatment abruptly or missing several doses can cause withdrawal-like symptoms. Symptoms may vary depending on how the drug works. This is sometimes called discontinuation syndrome. Work with your doctor to gradually and safely decrease your dose.

Withdrawal-like symptoms can include:

  • Agitation, irritability or anxiety
  • Nausea
  • Sweating
  • Flu-like symptoms, such as chills and muscle aches
  • Insomnia
  • Lethargy
  • Headache

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 may 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 specific 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's 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.

From Mayo Clinic to your inbox

Sign up for free, and stay up to date on research advancements, health tips and current health topics, like COVID-19, plus expertise on managing health.

To provide you with the most relevant and helpful information, and understand which information is beneficial, we may combine your email and website usage information with other information we have about you. If you are a Mayo Clinic patient, this could include protected health information. If we combine this information with your protected health information, we will treat all of that information as protected health information and will only use or disclose that information as set forth in our notice of privacy practices. You may opt-out of email communications at any time by clicking on the unsubscribe link in the e-mail.

March 30, 2022

  1. Depression: FDA-approved medications may help. U.S. Food and Drug Administration. https://www.fda.gov/consumers/consumer-updates/depression-fda-approved-medications-may-help. Accessed Aug. 13, 2019.
  2. Depression basics. National Institute of Mental Health. https://www.nimh.nih.gov/health/publications/depression/index.shtml. Accessed Aug. 13, 2019.
  3. Revisions to product labeling. U.S. Food and Drug Administration. https://www.fda.gov/media/77404/download. Accessed Aug. 13, 2019.
  4. Mental health medications. National Institute of Mental Health. https://www.nimh.nih.gov/health/topics/mental-health-medications/index.shtml#part_149856. Accessed Aug. 13, 2019.
  5. Gabriel M, et al. Antidepressant discontinuation syndrome. Canadian Medical Association Journal. 2017; doi:10.1503/cmaj.160991.
  6. What is pharmacogenomics? Genetics Home Reference. https://ghr.nlm.nih.gov/primer/genomicresearch/pharmacogenomics. Accessed Aug. 13, 2019.
  7. Hirsch M, et al. Tricyclic and tetracyclic drugs: Pharmacology, administration, and side effects. https://www.uptodate.com/contents/search. Accessed Aug. 19, 2019.
  8. Tricyclic antidepressants. Facts& Comparisons eAnswers. http://www.wolterskluwercdi.com/facts-comparisons-online/. Accessed Aug. 19, 2019.
  9. Tetracyclic antidepressants. Facts& Comparisons eAnswers. http://www.wolterskluwercdi.com/facts-comparisons-online/. Accessed Aug. 19, 2019.
  10. Ritter J, et al. Antidepressant drugs. In: Rang and Dale's Pharmacology. 9th ed. Elsevier; 2020.
  11. Amitriptyline (prescribing information). Accord Healthcare Inc.; 2018. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e6d2c80-fbc8-444e-bdd3-6a91fe1b95bd. Accessed Aug. 19, 2019.
  12. Amoxapine (prescribing information). Actavis Pharma Inc.; 2015. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a16297df-3158-48db-85e5-5cd506885556. Accessed Aug. 19, 2019.
  13. Norpramin (prescribing information). Validus Pharmaceuticals LLC; 2018. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70b562ea-9f21-4e4a-b3ed-0590b2892f6a. Accessed Sept. 12, 2019.
  14. Doxepin (prescribing information). Amneal Pharmaceuticals NY LLC; 2017. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=20bfb8af-7933-4e5c-a2b5-010659d9125b. Accessed Aug. 19, 2019.
  15. Tofranil (prescribing information). SpecGx LLC; 2017. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1827a5aa-733a-49d9-89d9-48ea0367b230. Accessed Sept.12, 2019.
  16. Pamelor (prescribing information). Mallinckrodt Inc.; 2019. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e17dc299-f52d-414d-ab6e-e809bd6f8acb. Accessed Aug. 19, 2019.
  17. Protriptyline (prescribing information). West-Ward Pharmaceuticals Corp.; 2016. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=700abc58-9362-4ef5-9d7a-dd3c4d364d0a. Accessed Aug. 26, 2019.
  18. Trimipramine (prescribing information). Breckenridge Pharmaceutical, Inc.; 2019. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4f31df66-7dc2-1f04-e054-00144ff88e88. Accessed Aug. 20, 2019.
  19. Maprotiline (prescribing information). Mylan Pharmaceuticals Inc.; 2014. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c3ca69e6-1ea0-4c2c-abcb-7264b2e79a87. Accessed Sept. 12, 2019.
  20. Krieger CA (expert opinion). Mayo Clinic. Sept. 11, 2019.

See more In-depth

See also

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

.

Which drug class is match with the correct neurotransmitter action?

Which drug class is matched with the correct neurotransmitter action? antidepressant. Which of the following statements best expresses the relationship between psychoanalysis and psychotherapy? Psychoanalysis is Freud's specific version of psychotherapy.

Which kind of drug is most closely associated with increasing the availability of serotonin?

SSRIs increase the amount of serotonin available to the brain, and are commonly prescribed for depression.

Which of the following was the purpose of lobotomies?

What is the purpose of a lobotomy? Lobotomies have been used as a radical therapeutic measure intended to calm patients with mental illnesses like schizophrenia and bipolar disorder.

Which of the following is most effectively treated with electroconvulsive therapy ECT?

Electroconvulsive Therapy (ECT) is the most effective treatment for depression.