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 They're effective, but they've generally been replaced by antidepressants that cause fewer side effects.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 impacting 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 absorption (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 cyclic antidepressants to treat depression:

Tricyclic antidepressants:

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

Maprotiline, a tetracyclic antidepressant, also is FDA approved for depression.

Sometimes cyclic antidepressants are used to treat conditions other than depression, such as 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:

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

Other possible side effects, among others, include:

  • Increased appetite leading to weight gain
  • Weight loss
  • 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 and imipramine 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.

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.

June 28, 2016 See more In-depth