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

Tricyclic and tetracyclic antidepressants, also called cyclic antidepressants, were among the earliest antidepressants developed. They're effective, but they've generally been replaced by antidepressants that cause fewer side effects. Other antidepressants are prescribed more often, but cyclic 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 ease depression by affecting naturally occurring chemical messengers (neurotransmitters), which are used to communicate between brain cells.

Cyclic antidepressants block the absorption (reuptake) of the neurotransmitters serotonin (ser-o-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. Most antidepressants work by changing the levels of one or more neurotransmitters.

Cyclic antidepressants also affect other chemical messengers, which can lead to a number of side effects.

Cyclic antidepressants approved to treat depression

Cyclic antidepressants are designated as tricyclic or tetracyclic, depending on the number of rings in their chemical structure — three (tri) or four (tetra). Those approved by the Food and Drug Administration to treat depression are listed below.

Tricyclic antidepressants:

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

Maprotiline is a tetracyclic antidepressant.

Some of these medications are available as liquids (oral solutions).

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

Side effects and cautions

Side effects of cyclic antidepressants vary somewhat from medication to medication and usually don't last long. The most common side effects of cyclic antidepressants include:

  • Dry mouth
  • Blurred vision
  • Constipation
  • Urinary retention
  • Drowsiness
  • Increased appetite leading to weight gain
  • Drop in blood pressure when moving from sitting to standing, which can cause lightheadedness
  • Increased sweating

Other side effects may include:

  • Disorientation or confusion, particularly in older people when the dosage is too high
  • Tremor
  • Increased or irregular heart rate
  • More-frequent seizures in people who have seizures
  • Difficulty achieving an erection, delayed orgasm or low sex drive

Read the package insert for additional side effects and talk to your doctor or pharmacist if you have questions.

Some tricyclic antidepressants are more likely to cause particular side effects. For example, amitriptyline, doxepin and trimipramine are more likely to make you sleepy than are other tricyclic antidepressants. Amitriptyline, doxepin and imipramine are more likely to cause weight gain than are other tricyclic antidepressants. Nortriptyline and desipramine appear to have better tolerated side effects.

July 19, 2013 See more In-depth