Tricyclic antidepressants (TCAs) were introduced in the late 1950s. They were the first class of antidepressants shown to be effective in well-controlled studies. TCAs are called tricyclic because their chemical structure traditionally contained three rings. Today, TCAs are often called cyclic antidepressants because some of the newer drugs in this category actually have four rings. Cyclic antidepressants are effective medications, though some people find their side effects difficult to tolerate. They are a good choice for some patients with treatment-resistant depression.

How Cyclic Antidepressants Work

Cyclic antidepressants block the reuptake of serotonin and norepinephrine, brain chemicals that are related to mood. By blocking the reabsorption of these chemicals, cyclic antidepressants increase the levels of serotonin and norepinephrine. This helps elevate mood.

Cyclic antidepressants also affect the action of acetylcholine, a brain chemical that affects muscle movement and the automatic (also known as autonomic) functions of the body, including secretions and digestion. Cyclic antidepressants block the effects of histamine, too. Neither of these actions is believed to affect depression; however, they explain some of the more troublesome side effects associated with cyclic antidepressants.

Who Should Take Cyclic Antidepressants?

Cyclic antidepressants are often used after other medications have failed to relieve depression. They are also used to treat obsessive compulsive disorder (OCD) and chronic bedwetting. In lower doses, cyclic antidepressants are used to prevent migraines and treat chronic pain. They are sometimes used to help individuals with panic disorder as well.

Patients with narrow-angle glaucoma, an enlarged prostate, urinary retention, heart problems, thyroid problems, or seizures should avoid cyclic antidepressants. Cyclic antidepressants can worsen urinary retention and cause abnormal heart rhythms or seizures. They can also affect vision and thyroid function.

Patients who drink alcohol frequently should also avoid cyclic antidepressants. Alcohol increases the sedating effects of cyclic antidepressants while blocking their antidepressant action.

Cyclic antidepressants can cause harmful side effects when taken with certain medications, including epinephrine (Epi-Pen) and cimetidine (Tagamet). They also affect blood sugar levels, so patients with diabetes who start a cyclic antidepressant will need to check their blood sugars frequently.

Pregnant women or women who are breastfeeding should talk to a physician before beginning or continuing treatment with cyclic antidepressants. Your physician will help you weigh any possible physical risks to you or your baby versus the continuing risk of untreated depression.

Possible Side Effects

Cycle antidepressants are more likely to cause constipation, weight gain, and sedation than new medications. However, different drugs have different effects. If you experience a troublesome side effect on one cyclic antidepressant, tell your doctor. Switching to another cyclic antidepressant may help.

Possible side effects include:

  • dry mouth
  • dry eye and/or blurred vision
  • dizziness
  • fatigue
  • headache
  • disorientation
  • seizure (especially with maprotiline)
  • drowsiness (especially  with desipramine and protriptyline)
  • constipation
  • urinary retention
  • sexual dysfunction (decreased libido/difficulty with orgasm)
  • low blood pressure
  • weight gain (especially with amitriptyline and doxepin)
  • nausea

Abruptly stopping cyclic antidepressant treatment can cause nausea, headache, dizziness, lethargy, and flu-like symptoms. Talk to your doctor before decreasing or stopping treatment. If you plan to stop treatment, it is general practice to taper the dose over time rather than to just stop the medication.

Brand Names

The generic names of cyclic antidepressants are listed below with their brand-name counterparts in parentheses.

  • amitriptyline (Elavil)
  • amoxapine (Asendin)
  • clomipramine (Anafranil)
  • desipramine (Norpramin)
  • doxepin (Sinequan)
  • imipramine (Tofranil)
  • maprotiline (Ludiomil)
  • nortriptyline (Pamelor)
  • protriptyline (Vivactil)
  • trimipramine (Surmontil)

What the Expert Says

Tricyclic antidepressants were the first antidepressants approved for use,” says Dr. Danny Carlat, M.D., associate clinical professor of psychiatry at Tufts University School of Medicine. “They are sometimes used after selective serotonin reuptake inhibitors (SSRIs) haven’t worked. They can, however, cause some side effects that can be really worrisome if you don’t monitor for them.”