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Tricyclic antidepressants and tetracyclic antidepressants

By Mayo Clinic staff
Original Article:  http://www.mayoclinic.com/health/antidepressants/MH00071
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Tricyclic antidepressants and tetracyclic antidepressants

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

By Mayo Clinic staff

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Tricyclic and tetracyclic antidepressants were among the earliest antidepressants developed. They're effective, but have generally been replaced by antidepressants that cause fewer side effects. Other antidepressants are prescribed more often, but these antidepressants are still a good option for some people. In certain cases, they relieve depression when other treatments have failed.

How tricyclic and tetracyclic antidepressants work

Tricyclic and tetracyclic antidepressants, also called cyclic antidepressants, ease depression by affecting chemical messengers in the brain (neurotransmitters). These naturally occurring brain chemicals are used to communicate between brain cells. Most antidepressants work by changing the levels of one or more neurotransmitters.

Cyclic antidepressants block the absorption (reuptake) of the neurotransmitters serotonin (ser-oh-TOE-nin) and norepinephrine (nor-ep-ih-NEF-rin), making more of these chemicals available in the brain. This seems to help brain cells send and receive messages, which in turn boosts mood. These antidepressants also affect other chemical messengers, which can lead to a number of side effects.

Cyclic antidepressants approved to treat depression

Tricyclic and tetracyclic antidepressants approved by the Food and Drug Administration to treat depression, with their generic names followed by brand names in parentheses, include:

  • Amitriptyline
  • Amoxapine
  • Desipramine (Norpramin)
  • Doxepin
  • Imipramine (Tofranil, Tofranil-PM)
  • Maprotiline
  • Nortriptyline (Pamelor)
  • Protriptyline (Vivactil)
  • Trimipramine (Surmontil)

Some of these medications come in forms that must be injected or as liquids (oral solutions).

Sometimes, these antidepressants are used to treat conditions other than depression.

Side effects of tricyclic antidepressants

Side effects of cyclic antidepressants vary somewhat from medication to medication. They can include:

  • Drowsiness
  • Dry mouth
  • Blurred vision
  • Constipation
  • Urinary retention
  • Dizziness
  • Delayed orgasm and low sex drive, particularly in men
  • Increased heart rate
  • Disorientation or confusion
  • Low blood pressure, which can cause lightheadedness
  • Increased appetite
  • Weight gain
  • Fatigue
  • Headache
  • Sensitivity to sunlight
  • Nausea
  • Seizures (particularly with maprotiline)

Some cyclic antidepressants are more likely to cause particular side effects. For example, desipramine and protriptyline are more likely to make you sleepy than do other cyclic antidepressants. Amitriptyline and doxepin are more likely to cause weight gain than do other cyclic antidepressants. Choosing one particular cyclic antidepressant over another may help you avoid particular side effects.

Safety concerns with cyclic antidepressants

There are a number of things to consider before taking a cyclic antidepressant:

  • Antidepressants and pregnancy. Some antidepressants may harm your child 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 provider about the possible dangers. Don't stop taking your medication without contacting your doctor first.
  • Drug interactions. When taking an antidepressant, be sure to tell your doctor about any other medications or supplements you're taking. Some antidepressants can cause dangerous reactions when combined with certain medications or herbal remedies.
  • Serotonin syndrome. Rarely, a cyclic antidepressant can cause dangerously high levels of serotonin. This is known as serotonin syndrome. It most often occurs when two medications that raise serotonin are combined. These include other antidepressants, medications for certain health conditions and the herbal supplement St. John's wort. Signs and symptoms of serotonin syndrome include confusion, rapid or irregular heartbeat, dilated pupils, fever and unconsciousness. Seek immediate medical attention if you have any of these signs or symptoms.
  • Safety and blood tests. High doses of cyclic antidepressants can cause serious health problems. You may need periodic blood tests to check levels of a cyclic antidepressant in your bloodstream, particularly if you're taking a high dose.
  • Chronic health conditions. Cyclic antidepressants can cause problems in people with certain health conditions. If you have narrow-angle glaucoma, an enlarged prostate, heart problems, thyroid problems or a history of seizures, talk to your doctor about whether a cyclic antidepressant is a safe choice for you.
  • Blood sugar and diabetes. If you have diabetes, you may need to check your blood sugar often while taking a cyclic antidepressant. These medications can affect blood sugar levels.
  • Drowsiness. Cyclic antidepressants can make you drowsy and may reduce your ability to drive or use machinery safely.

Stopping treatment with cyclic antidepressants

Cyclic antidepressants aren't considered addictive. However, stopping treatment abruptly or missing several doses can cause withdrawal-like symptoms, including:

  • Nausea
  • Headache
  • Dizziness
  • Lethargy
  • Flu-like symptoms

This is sometimes called discontinuation syndrome. Work with your doctor to gradually decrease your dose.

Suicide risk and antidepressants

The Food and Drug Administration (FDA) requires that all antidepressants carry a warning that some children, adolescents and young adults may be at increased risk of suicide when taking antidepressants. Anyone taking an antidepressant should be watched closely for worsening depression or unusual behavior — especially in the first few weeks after starting an antidepressant. Keep in mind, antidepressants are more likely to reduce suicide risk in the long run by improving mood.

Finding the right antidepressant

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

Inherited traits play a role in how antidepressants affect you. In some cases, DNA tests such as cytochrome P450 (CYP450) tests may give clues as to whether an antidepressant is likely to ease symptoms or cause side effects. DNA testing isn't widely used yet, but is becoming more common.

It can take a long time to find the best treatment for depression. It takes several weeks or longer before an antidepressant is fully effective and for initial side effects to ease up. You may need to try several antidepressants before you find the right one, but hang in there. With patience, you and your doctor can find a medication that works well for you.

References
  1. Schatzberg AF, et al. Antidepressants: Introduction. In: Schatzberg AF, et al. Manual of Clinical Psychopharmacology. 7th ed. Arlington, Va.: American Psychiatric Publishing; 2010. http://www.psychiatryonline.com/content.aspx?aID=600624. Accessed Oct. 5, 2010.
  2. Fava M, et al. Antidepressants. In: Stern TA, et al. Massachusetts General Hospital Comprehensive Clinical Psychiatry. Philadelphia, Pa.: Mosby. 2008. http://www.mdconsult.com/das/book/body/221513496-3/0/1657/421.html?tocnode=57543329&fromURL=421.html#4-u1.0-B978-0-323-04743-2..50045-7_1104. Accessed Oct. 5, 2010.
  3. Hirsch M, et al. Tricyclic and tetracyclic drugs for treating depressed adults http://www.uptodate.com/home/index.html. Accessed Oct. 7, 2010.
MH00071 Dec. 9, 2010

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